Breast CancerPhase 4NCT02445586
Safety Study of Pertuzumab (in Combination With Trastuzumab and Docetaxel) in Indian Participants With Breast Cancer
A Phase 4 study testing Docetaxel, Pertuzumab and Trastuzumab in people with Breast Cancer, run by Hoffmann-La Roche at 9 sites in India.
Trial summary
This is a Phase 4, single-arm, open-label, multicenter study to assess the safety and efficacy of pertuzumab in combination with trastuzumab and docetaxel for the treatment of participants with human epidermal growth factor receptor 2 (HER2)-positive advanced (locally recurrent, unresectable, or metastatic) breast… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Docetaxel, Pertuzumab and Trastuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 9 sitesIndia
- Study dates
- 17 Aug 2015to 26 Sep 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly-effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the participant and/or partner
- Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally recurrent disease not amenable to curative resection; participants with measurable and/or non-measurable disease are eligible
- Known and documented HER2-positive
- Known and documented LVEF of at least 50 percent (%)
- Adequate organ function
- A negative serum beta-human chorionic gonadotropin (beta-HCG) test for women of childbearing potential (premenopausal, or less than [<] 12 months of amenorrhea post-menopause, and women who have not undergone surgical sterilization [absence of ovaries and/or uterus]) within 7 days prior to the first dose of study treatment with the result available prior to first dosing
Who cannot join
- Previous systemic non-hormonal anti-cancer therapy for the metastatic or locally recurrent disease
- Pregnant or lactating women
- Current clinical or radiographic evidence of central nervous system (CNS) metastases
- Disease progression while receiving or within 12 months of completion of trastuzumab and/or lapatinib treatment in the adjuvant or neo-adjuvant setting
- History of LVEF decline to below 50% during or after prior trastuzumab adjuvant or neo-adjuvant therapy
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
India9 sites
M S Ramaiah Memorial Hospital
Bangalore, 560054
MAX Balaji Hospital
Delhi, 110092
Indo-American Cancer Hospital & Research Center
Hyderabad, Telangana, 500034
TATA Medical Centre; Medical Oncology
Kolkata, West Bengal, 700156
Tata Memorial Hospital; Dept of Medical Oncology
Mumbai, Maharashtra, 400012
Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute
Mumbai, Maharashtra, 400053
Rajiv Gandhi Cancer Institute & Research Center
New Delhi, National Capital Territory of Delhi, 110 085
Jehangir Clinical Development Centre Pvt. Ltd; Cancer Research Room
Pune, Maharashtra, 411001
Christian Medical College & Hospital; Medicine
Vellore, Tamil Nadu, 632004
About this study
Official title: A Phase IV, Multicenter, Open-Label, Single-Arm Study of Pertuzumab (in Combination With Trastuzumab and Docetaxel) in First Line Treatment of Indian Patients With HER2-Positive Advanced (Metastatic or Locally Recurrent) Breast Cancer
This is a Phase 4, single-arm, open-label, multicenter study to assess the safety and efficacy of pertuzumab in combination with trastuzumab and docetaxel for the treatment of participants with human epidermal growth factor receptor 2 (HER2)-positive advanced (locally recurrent, unresectable, or metastatic) breast cancer.
- Conditions
- Breast Cancer
- Being tested
- Docetaxel, Pertuzumab, Trastuzumab
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DocetaxelDrug
Participants will receive docetaxel in line with locally approved Prescribing Information. After Cycle 6 (cycle length = 21 days), continuation of docetaxel treatment will be at the discretion of the investigator. Docetaxel will be administered after pertuzumab and trastuzumab.
PertuzumabDrug
Also called Perjeta®
Participants will receive pertuzumab at an initial dose of 840 milligrams (mg) as a 60-minute intravenous infusion on Cycle 1 Day 1 (cycle length = 21 days), followed by every 3 weeks at a dose of 420 mg as a 30 to 60-minute intravenous infusion until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
TrastuzumabDrug
Also called Herceptin®, Herclon®
Participants will receive trastuzumab at an initial dose of 8 milligrams per kilogram (mg/kg) as a 90-minute intravenous infusion on Cycle 1 Day 1 (cycle length = 21 days), followed by every 3 weeks at a dose of 6 mg/kg as a 30 to 90-minute intravenous infusion until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
| Study group | Role | What they receive |
|---|---|---|
| Pertuzumab in Combination with Trastuzumab and Docetaxel | Experimental | Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. Receives: Drug: Docetaxel; Drug: Pertuzumab; Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Number of Participants by the Number of Serious Adverse Events Reported Per Participant
The number of participants with serious adverse events was counted in the four following categories for number of events reported per participant: greater than or equal to (≥) 1, 1, greater than (>) 1, or 0 serious adverse events. Participants with multiple occurrences of events (the ≥1 and >1 serious adverse event categories) were only counted once per category.
Measured: From Baseline until end of study (up to approximately 3 years)
Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)
The number of participants with serious adverse events was counted by the initial and most extreme levels of severity of the adverse event, assessed as Grades 1-5 according to NCI CTCAE v4.03. Any adverse event not specifically listed in NCI CTCAE v4.03 was assessed according to the following grades of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening or urgent intervention indicated; and Grade 5 is death related to adverse event. The terms "severe" and "serious" are not synonymous. Severity refers to the intensity of an adverse event. The seriousness of an adverse event is based on whether it meets any of the criteria set out in the protocol's definition of a serious adverse event. Severity and seriousness were independently assessed for each adverse event. Participants with multiple occurrences of serious adverse events of the same severity were only counted once per severity category.
Measured: From Baseline until end of study (up to approximately 3 years)
Number of Participants With Serious Adverse Events Related to Docetaxel
The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with docetaxel, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Measured: From Baseline until end of study (up to approximately 3 years)
Number of Participants With Serious Adverse Events Related to Pertuzumab
The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with pertuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Measured: From Baseline until end of study (up to approximately 3 years)
Number of Participants With Serious Adverse Events Related to Trastuzumab
The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with trastuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Measured: From Baseline until end of study (up to approximately 3 years)
Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug
The number of participants with serious adverse events was counted by the type of action taken with the study drug (docetaxel, pertuzumab, and trastuzumab) in response to the adverse event in the three following categories: infusion reduced, temporarily interrupted, or permanently discontinued. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of serious adverse events that required the same action to be taken with the study drug were only counted once per category.
Measured: From Baseline until end of study (up to approximately 3 years)
Overall Number of Participants With Serious Adverse Events by Event Outcome
The number of participants with serious adverse events was counted by the event outcome in the six following categories: fatal, recovered/resolved, recovered/resolved with sequelae, recovering/resolving, not recovered/not resolved, or unknown. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of serious adverse events with the same outcome were only counted once per category.
Measured: From Baseline until end of study (up to approximately 3 years)
Number of Participants With Hematological Abnormalities Reported as Serious Adverse Events
The number of participants with hematological laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Measured: From Baseline until end of study (up to approximately 3 years)
Number of Participants With Serum Chemistry Abnormalities Reported as Serious Adverse Events
The number of participants with serum chemistry laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Measured: From Baseline until end of study (up to approximately 3 years)
Number of Participants With Coagulation Abnormalities Reported as Serious Adverse Events
The number of participants with coagulation laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Measured: From Baseline until end of study (up to approximately 3 years)
Number of Participants Who Died Due to a Serious Adverse Event by Cause of Death
The number of participants who died due to a serious adverse event was counted by the cause of death.
Measured: From Baseline until end of study (up to approximately 3 years)
Overall Number of Participants by the Number of Non-Serious Adverse Events Reported Per Participant
The number of participants with non-serious adverse events was counted in the four following categories for number of events reported per participant: greater than or equal to (≥) 1, 1, greater than (>) 1, or 0 non-serious adverse events. Participants with multiple occurrences of events (the ≥1 and >1 non-serious adverse event categories) were only counted once per category.
Measured: From Baseline until end of study (up to approximately 3 years)
Overall Number of Participants With Non-Serious Adverse Events by Severity, According to NCI-CTCAE v4.03
The number of participants with non-serious adverse events was counted by the severity level of the adverse event, assessed as Grades 1-5 according to NCI CTCAE v4.03. Any adverse event not specifically listed in NCI CTCAE v4.03 was assessed according to the following grades of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening or urgent intervention indicated; and Grade 5 is death related to adverse event. The terms "severe" and "serious" are not synonymous. Severity refers to the intensity of an adverse event. The seriousness of an adverse event is based on whether it meets any of the criteria set out in the protocol's definition of a serious adverse event. Severity and seriousness were independently assessed for each adverse event. Participants with multiple occurrences of non-serious adverse events of the same severity were only counted once per severity category.
Measured: From Baseline until end of study (up to approximately 3 years)
Number of Participants With Non-Serious Adverse Events Related to Docetaxel
The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with docetaxel, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Measured: From Baseline until end of study (up to approximately 3 years)
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab
The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with pertuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Measured: From Baseline until end of study (up to approximately 3 years)
Number of Participants With Non-Serious Adverse Events Related to Trastuzumab
The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with trastuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Measured: From Baseline until end of study (up to approximately 3 years)
Overall Number of Participants With Non-Serious Adverse Events by Chemotherapy Adjustment With Docetaxel and/or Trastuzumab
The number of participants with non-serious adverse events was counted by the type of action taken with docetaxel and/or trastuzumab in response to the adverse event in the three following categories: no adjustment, dosage modified/interrupted, and discontinued. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events that required the same action to be taken with the study drug were only counted once per category.
Measured: From Baseline until end of study (up to approximately 3 years)
Overall Number of Participants With Non-Serious Adverse Events by Action Taken With Pertuzumab
The number of participants with non-serious adverse events was counted by the type of action taken with pertuzumab in response to the adverse event in the three following categories: no action taken, infusion slow down, infusion interrupted, and appropriate medical therapies administered. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events that required the same action to be taken with the study drug were only counted once per category.
Measured: From Baseline until end of study (up to approximately 3 years)
Overall Number of Participants With Non-Serious Adverse Events by Event Outcome
The number of participants with non-serious adverse events was counted by the event outcome in the four following categories: resolved with no sequelae, resolved with sequelae, unresolved, or death. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events with the same outcome were only counted once per category.
Measured: From Baseline until end of study (up to approximately 3 years)
Overall Number of Participants With Non-Serious Adverse Events by Treatment Emergence (TEAE Versus Non-TEAE)
The number of participants with non-serious adverse events was counted according to whether the event was considered a treatment emergent adverse event (TEAE), which is defined as an adverse event that emerges during treatment, having been absent pretreatment, or worsens relative to the pretreatment state. Participants with multiple occurrences of non-serious adverse events were only counted once per category.
Measured: From Baseline until end of study (up to approximately 3 years)
Number of Participants With Hematological Abnormalities Reported as Non-Serious Adverse Events
The number of participants with hematological laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Measured: From Baseline until end of study (up to approximately 3 years)
Number of Participants With Serum Chemistry Abnormalities Reported as Non-Serious Adverse Events
The number of participants with serum chemistry laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Measured: From Baseline until end of study (up to approximately 3 years)
Number of Participants With Coagulation Abnormalities Reported as Non-Serious Adverse Events
The number of participants with coagulation laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Measured: From Baseline until end of study (up to approximately 3 years)
Number of Participants With Congestive Heart Failure
Measured: From Baseline until end of study (up to approximately 3 years)
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Left ventricular ejection fraction (LVEF) assessments were performed within 42 days of enrollment and every three treatment cycles by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan; ECHO was the preferred method. In order to be eligible for this study, an LVEF of ≥50% was required at screening. The same method of LVEF assessment for each participant must have been used throughout the study, and to the extent possible, have been obtained at the same institution.
Measured: Baseline, every 3 cycles (1 cycle is 21 days) until treatment discontinuation, at Safety Follow-Up (28 days after last dose of study drug) and every 3 months thereafter until end of study (up to approximately 3 years)
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time
Left ventricular ejection fraction (LVEF) assessments were performed within 42 days of enrollment and every three treatment cycles by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan; ECHO was the preferred method. In order to be eligible for this study, an LVEF greater than or equal to (≥)50% was required at screening. The same method of LVEF assessment for each participant must have been used throughout the study, and to the extent possible, have been obtained at the same institution. The following are definitions for the three categories of LVEF findings: 'Normal' was defined as LVEF ≥45%; 'Abnormal but not clinically significant' was defined as LVEF <45% but not clinically significant in the investigator's judgment; 'Abnormal and clinically significant' was defined as LVEF <45% and clinically significant in the investigator's judgment.
Measured: Baseline, every 3 cycles (1 cycle is 21 days) until treatment discontinuation, at Safety Follow-Up (28 days after last dose of study drug) and every 3 months thereafter until end of study (up to approximately 3 years)
Number of Participants With Adverse Events Leading to Treatment Discontinuation
The number of participants with any adverse event (serious or non-serious) that led to treatment discontinuation during the study was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one adverse event that led to treatment discontinuation may have been reported per participant.
Measured: From Baseline until end of study (up to approximately 3 years)
Secondary outcomes (8)
Overall Response Rate
The overall response rate (ORR) was defined as the percentage of participants with best overall response of Complete Response (CR) or Partial Response (PR), confirmed by repeat assessment no less than 4 weeks after the response criteria were first met, using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Participants who either had not achieved CR or PR or were without a post-baseline tumor assessment were to be considered non-responders. All measurable and non-measurable lesions were documented at screening and re-assessed at each subsequent tumor evaluation. Response was assessed by the investigator on the basis of physical examinations, computed tomography (CT) scans, and magnetic resonance imaging (MRI). The same radiographic procedure was used throughout the study, and assessments were preferably performed by the same evaluator. The 95% confidence intervals were calculated using Clopper-Pearson methodology.
Measured: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)
Number of Participants by Best Overall Response
The best overall response was defined as the best response, out of all the documented responses over the course of the entire study period, using RECIST v1.1. All measurable and non-measurable lesions were documented at screening and re-assessed at each subsequent tumor evaluation. Response was assessed by the investigator on the basis of physical examinations, computed tomography (CT) scans, and magnetic resonance imaging (MRI). The same radiographic procedure was used throughout the study, and assessments were preferably performed by the same evaluator.
Measured: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)
Number of Participants With Disease Progression or Death or Who Were Censored for Progression-Free Survival Analysis
Progression-free survival (PFS) was defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Participants who had not progressed or died or were lost to follow up at the time of the analysis were censored on the last visit at which assessment for progression was done (2 years after the last participant was enrolled). PFS was analyzed by the Kaplan-Meier method.
Measured: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)
Median Duration of Progression-Free Survival
Progression-free survival (PFS) was defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Participants who had not progressed or died, or were lost to follow up at the time of the analysis, were censored on the last visit at which assessment for progression was done (2 years after the last participant was enrolled). PFS was analyzed by the Kaplan-Meier method.
Measured: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months
Progression-free survival (PFS) was defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Participants who had not progressed, died or were lost to follow up at the time of the analysis were censored on the last visit at which assessment for progression was done (2 years after the last participant was enrolled). PFS was analyzed by the Kaplan-Meier method.
Measured: Months 2, 3, 5, 6, 7, 8, 9, 11, 13, 15, 16, 17, 18, 19, 23, 24, 25, 27, 29, and 32
Number of Participants Who Died or Were Censored for Overall Survival Analysis
Overall survival was defined as the time from enrollment to the the date of death from any cause. Participants who were alive at the time of the analysis, dropped out of the study, or lost to follow-up were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication, and participants with no post-baseline information were censored at baseline. Overall survival was analyzed by the Kaplan-Meier method.
Measured: From Baseline up to death from any cause (up to approximately 3 years)
Median Duration of Overall Survival
Overall survival was defined as the time from enrollment to the the date of death from any cause. Participants who were alive at the time of the analysis, dropped out of the study, or lost to follow-up were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication, and participants with no post-baseline information were censored at baseline. Overall survival was analyzed by the Kaplan-Meier method.
Measured: From Baseline up to death from any cause (up to approximately 3 years)
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months
Overall survival was defined as the time from enrollment to the the date of death from any cause. Participants who were alive at the time of the analysis, dropped out of the study, or lost to follow-up were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication, and participants with no post-baseline information were censored at baseline. Overall survival was analyzed by the Kaplan-Meier method.
Measured: Months 3, 9, 13, 14, 15, 18, 19, 20, 24, 25, 27, 32, 33, and 34
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2015 (estimated)
- Study start17 Aug 2015
- Primary completion26 Sep 2018
- Study completion26 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Anil Kukreja, MD, Study director, Roche Products (India) Pvt. Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02445586
- Sponsor's protocol ID
- ML29282
- Status last verified
- Oct 2019
- First submitted
- 13 May 2015
- Last updated
- 29 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IV, Multicenter, Open-Label, Single-Arm Study of Pertuzumab (in Combination With Trastuzumab and Docetaxel) in First Line Treatment of Indian Patients With HER2-Positive Advanced (Metastatic or Locally Recurrent) Breast Cancer
- ClinicalTrials.gov ID
- NCT02445586
- Acronym / sponsor ID
- ML29282
- Conditions
- Breast Cancer
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 17 Aug 2015 (actual)
- Primary completion
- 26 Sep 2018 (actual)
- Study completion
- 26 Sep 2018 (actual)
- First posted
- 15 May 2015 (estimated)
- Results
- Posted 29 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 4, single-arm, open-label, multicenter study to assess the safety and efficacy of pertuzumab in combination with trastuzumab and docetaxel for the treatment of participants with human epidermal growth factor receptor 2 (HER2)-positive advanced (locally recurrent, unresectable, or metastatic) breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pertuzumab in Combination with Trastuzumab and Docetaxel | Experimental | Drug: Docetaxel, Drug: Pertuzumab, Drug: TrastuzumabParticipants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly-effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the participant and/or partner
- Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally recurrent disease not amenable to curative resection; participants with measurable and/or non-measurable disease are eligible
- Known and documented HER2-positive
- Known and documented LVEF of at least 50 percent (%)
- Adequate organ function
Key exclusion criteria (5 listed)
- Previous systemic non-hormonal anti-cancer therapy for the metastatic or locally recurrent disease
- Pregnant or lactating women
- Current clinical or radiographic evidence of central nervous system (CNS) metastases
- Disease progression while receiving or within 12 months of completion of trastuzumab and/or lapatinib treatment in the adjuvant or neo-adjuvant setting
- History of LVEF decline to below 50% during or after prior trastuzumab adjuvant or neo-adjuvant therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DocetaxelParticipants will receive docetaxel in line with locally approved Prescribing Information. After Cycle 6 (cycle length = 21 days), continuation of docetaxel treatment will be at the discretion of the investigator. Docetaxel will be administered after pertuzumab and trastuzumab. | Drug | Pertuzumab in Combination with Trastuzumab and Docetaxel |
| PertuzumabAlso: Perjeta®Participants will receive pertuzumab at an initial dose of 840 milligrams (mg) as a 60-minute intravenous infusion on Cycle 1 Day 1 (cycle length = 21 days), followed by every 3 weeks at a dose of 420 mg as a 30 to 60-minute intravenous infusion until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. | Drug | Pertuzumab in Combination with Trastuzumab and Docetaxel |
| TrastuzumabAlso: Herceptin®, Herclon®Participants will receive trastuzumab at an initial dose of 8 milligrams per kilogram (mg/kg) as a 90-minute intravenous infusion on Cycle 1 Day 1 (cycle length = 21 days), followed by every 3 weeks at a dose of 6 mg/kg as a 30 to 90-minute intravenous infusion until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. | Drug | Pertuzumab in Combination with Trastuzumab and Docetaxel |
Primary outcome
Overall Number of Participants by the Number of Serious Adverse Events Reported Per Participant
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with serious adverse events was counted in the four following categories for number of events reported per participant: greater than or equal to (≥) 1, 1, greater than (>) 1, or 0 serious adverse events. Participants with multiple occurrences of events (the ≥1 and >1 serious adverse event categories) were only counted once per category.
Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with serious adverse events was counted by the initial and most extreme levels of severity of the adverse event, assessed as Grades 1-5 according to NCI CTCAE v4.03. Any adverse event not specifically listed in NCI CTCAE v4.03 was assessed according to the following grades of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening or urgent intervention indicated; and Grade 5 is death related to adverse event. The terms "severe" and "serious" are not synonymous. Severity refers to the intensity of an adverse event. The seriousness of an adverse event is based on whether it meets any of the criteria set out in the protocol's definition of a serious adverse event. Severity and seriousness were independently assessed for each adverse event. Participants with multiple occurrences of serious adverse events of the same severity were only counted once per severity category.
Number of Participants With Serious Adverse Events Related to Docetaxel
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with docetaxel, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Number of Participants With Serious Adverse Events Related to Pertuzumab
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with pertuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Number of Participants With Serious Adverse Events Related to Trastuzumab
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with trastuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with serious adverse events was counted by the type of action taken with the study drug (docetaxel, pertuzumab, and trastuzumab) in response to the adverse event in the three following categories: infusion reduced, temporarily interrupted, or permanently discontinued. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of serious adverse events that required the same action to be taken with the study drug were only counted once per category.
Overall Number of Participants With Serious Adverse Events by Event Outcome
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with serious adverse events was counted by the event outcome in the six following categories: fatal, recovered/resolved, recovered/resolved with sequelae, recovering/resolving, not recovered/not resolved, or unknown. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of serious adverse events with the same outcome were only counted once per category.
Number of Participants With Hematological Abnormalities Reported as Serious Adverse Events
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with hematological laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Number of Participants With Serum Chemistry Abnormalities Reported as Serious Adverse Events
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with serum chemistry laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Number of Participants With Coagulation Abnormalities Reported as Serious Adverse Events
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with coagulation laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.
Number of Participants Who Died Due to a Serious Adverse Event by Cause of Death
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants who died due to a serious adverse event was counted by the cause of death.
Overall Number of Participants by the Number of Non-Serious Adverse Events Reported Per Participant
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with non-serious adverse events was counted in the four following categories for number of events reported per participant: greater than or equal to (≥) 1, 1, greater than (>) 1, or 0 non-serious adverse events. Participants with multiple occurrences of events (the ≥1 and >1 non-serious adverse event categories) were only counted once per category.
Overall Number of Participants With Non-Serious Adverse Events by Severity, According to NCI-CTCAE v4.03
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with non-serious adverse events was counted by the severity level of the adverse event, assessed as Grades 1-5 according to NCI CTCAE v4.03. Any adverse event not specifically listed in NCI CTCAE v4.03 was assessed according to the following grades of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening or urgent intervention indicated; and Grade 5 is death related to adverse event. The terms "severe" and "serious" are not synonymous. Severity refers to the intensity of an adverse event. The seriousness of an adverse event is based on whether it meets any of the criteria set out in the protocol's definition of a serious adverse event. Severity and seriousness were independently assessed for each adverse event. Participants with multiple occurrences of non-serious adverse events of the same severity were only counted once per severity category.
Number of Participants With Non-Serious Adverse Events Related to Docetaxel
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with docetaxel, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with pertuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Number of Participants With Non-Serious Adverse Events Related to Trastuzumab
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with trastuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Overall Number of Participants With Non-Serious Adverse Events by Chemotherapy Adjustment With Docetaxel and/or Trastuzumab
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with non-serious adverse events was counted by the type of action taken with docetaxel and/or trastuzumab in response to the adverse event in the three following categories: no adjustment, dosage modified/interrupted, and discontinued. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events that required the same action to be taken with the study drug were only counted once per category.
Overall Number of Participants With Non-Serious Adverse Events by Action Taken With Pertuzumab
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with non-serious adverse events was counted by the type of action taken with pertuzumab in response to the adverse event in the three following categories: no action taken, infusion slow down, infusion interrupted, and appropriate medical therapies administered. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events that required the same action to be taken with the study drug were only counted once per category.
Overall Number of Participants With Non-Serious Adverse Events by Event Outcome
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with non-serious adverse events was counted by the event outcome in the four following categories: resolved with no sequelae, resolved with sequelae, unresolved, or death. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events with the same outcome were only counted once per category.
Overall Number of Participants With Non-Serious Adverse Events by Treatment Emergence (TEAE Versus Non-TEAE)
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with non-serious adverse events was counted according to whether the event was considered a treatment emergent adverse event (TEAE), which is defined as an adverse event that emerges during treatment, having been absent pretreatment, or worsens relative to the pretreatment state. Participants with multiple occurrences of non-serious adverse events were only counted once per category.
Number of Participants With Hematological Abnormalities Reported as Non-Serious Adverse Events
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with hematological laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Number of Participants With Serum Chemistry Abnormalities Reported as Non-Serious Adverse Events
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with serum chemistry laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Number of Participants With Coagulation Abnormalities Reported as Non-Serious Adverse Events
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with coagulation laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.
Number of Participants With Congestive Heart Failure
Time frame: From Baseline until end of study (up to approximately 3 years)
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Time frame: Baseline, every 3 cycles (1 cycle is 21 days) until treatment discontinuation, at Safety Follow-Up (28 days after last dose of study drug) and every 3 months thereafter until end of study (up to approximately 3 years)
Left ventricular ejection fraction (LVEF) assessments were performed within 42 days of enrollment and every three treatment cycles by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan; ECHO was the preferred method. In order to be eligible for this study, an LVEF of ≥50% was required at screening. The same method of LVEF assessment for each participant must have been used throughout the study, and to the extent possible, have been obtained at the same institution.
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time
Time frame: Baseline, every 3 cycles (1 cycle is 21 days) until treatment discontinuation, at Safety Follow-Up (28 days after last dose of study drug) and every 3 months thereafter until end of study (up to approximately 3 years)
Left ventricular ejection fraction (LVEF) assessments were performed within 42 days of enrollment and every three treatment cycles by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan; ECHO was the preferred method. In order to be eligible for this study, an LVEF greater than or equal to (≥)50% was required at screening. The same method of LVEF assessment for each participant must have been used throughout the study, and to the extent possible, have been obtained at the same institution. The following are definitions for the three categories of LVEF findings: 'Normal' was defined as LVEF ≥45%; 'Abnormal but not clinically significant' was defined as LVEF <45% but not clinically significant in the investigator's judgment; 'Abnormal and clinically significant' was defined as LVEF <45% and clinically significant in the investigator's judgment.
Number of Participants With Adverse Events Leading to Treatment Discontinuation
Time frame: From Baseline until end of study (up to approximately 3 years)
The number of participants with any adverse event (serious or non-serious) that led to treatment discontinuation during the study was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one adverse event that led to treatment discontinuation may have been reported per participant.
8 secondary outcomes
Overall Response Rate
Time frame: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)
Number of Participants by Best Overall Response
Time frame: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)
Number of Participants With Disease Progression or Death or Who Were Censored for Progression-Free Survival Analysis
Time frame: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)
Median Duration of Progression-Free Survival
Time frame: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months
Time frame: Months 2, 3, 5, 6, 7, 8, 9, 11, 13, 15, 16, 17, 18, 19, 23, 24, 25, 27, 29, and 32
Number of Participants Who Died or Were Censored for Overall Survival Analysis
Time frame: From Baseline up to death from any cause (up to approximately 3 years)
Median Duration of Overall Survival
Time frame: From Baseline up to death from any cause (up to approximately 3 years)
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months
Time frame: Months 3, 9, 13, 14, 15, 18, 19, 20, 24, 25, 27, 32, 33, and 34
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anil Kukreja, MD study director
Roche Products (India) Pvt. Ltd.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Docetaxel, Pertuzumab and Trastuzumab in people with Breast Cancer, run by Hoffmann-La Roche at 9 sites in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Number of Participants by the Number of Serious Adverse Events Reported Per Participant (time frame: From Baseline until end of study (up to approximately 3 years)). The study lists 27 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2019.