Breast CancerPhase 1/2NCT02139358
Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer
A Phase 1/2 study testing Gemcitabine, Trastuzumab and Pertuzumab in people with Breast Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the safety and activity of gemcitabine plus trastuzumab and pertuzumab in patients with metastatic human epidermal growth factor receptor 2 (HER2)+ breast cancer who have progressed on at least one prior line of chemotherapy plus HER2 targeted agent such as T-DM1, trastuzumab… 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?
- Gemcitabine, Trastuzumab and Pertuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Sep 2014to 16 Mar 2020
- Phase
- Phase 1/2
- 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
- Adult males or females (aged 18 or older) with histologically confirmed, metastatic human epidermal growth factor receptor 2 (HER2)+ (by immunohistochemistry (IHC) 3+ or fluorescence in situ hydridization (FISH) ratio ≥ 2.0) breast cancer
- Have progressed on at least one prior line of chemotherapy plus HER2 directed therapy such as trastuzumab and/or pertuzumab in the metastatic setting. T-DM1 would count as a line of therapy and patients previously treated with T-DM1 are eligible.
- Have not been treated with gemcitabine in the metastatic setting
- Measurable disease per Response Evaluation in Solid Tumors (RECIST) 1.1 criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 2≤
- Left Ventricular Ejection Fraction (LVEF) ≥ 50% at baseline as determined by either echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)
Show all 11Show fewer
- Adequate bone marrow function as indicated by the following: absolute neutrophil count (ANC) >1500/µL; Platelets ≥100,000/µL; Hemoglobin >10 g/dL
- Adequate renal function, as indicated by creatinine ≤1.5x upper limit of normal (ULN)
- Adequate liver function, as indicated by bilirubin ≤1.5x ULN, aspartic transaminase (AST) or alanine transaminase (ALT) <2x ULN unless related to metastatic breast cancer to the liver (in which case AST/ALT < 5x ULN is allowed).
- Signed informed consent
- Adequate birth control in sexually active women of childbearing potential
Who cannot join
- Active uncontrolled infection or major concurrent illness which in the opinion of the investigator would render the participant unsafe to proceed with the study
- Uncontrolled central nervous system (CNS) metastases. Treated, non-progressing CNS disease (documented by brain magnetic resonance imaging [MRI]) off corticosteroids for at least 1 month potential participants are eligible.
- Women who are pregnant or lactating
- Prior chemotherapy within the last 3 weeks (last 6 weeks for nitrosureas/mitomycin)
- Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation)
- Other concomitant active malignancies
Show all 10Show fewer
- History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias
- Ejection fraction <50% or below the lower limit of the institutional normal range, whichever is lower
- Hypersensitivity to any of the study medications
- Untreated psychiatric conditions preventing informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
The purpose of this study is to evaluate the safety and activity of gemcitabine plus trastuzumab and pertuzumab in patients with metastatic human epidermal growth factor receptor 2 (HER2)+ breast cancer who have progressed on at least one prior line of chemotherapy plus HER2 targeted agent such as T-DM1, trastuzumab, or lapatinib.
- Conditions
- Breast Cancer
- Being tested
- Gemcitabine, Trastuzumab, Pertuzumab
- Keywords
- Breast - Female, Metastatic, HER2+
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Also called GEMZAR®
The Phase I trial will start at the recommended phase II dose (RP2D) for gemcitabine but will have a de-escalation dose levels in the event that an unacceptable toxicity requires dose reduction. Dose level 0 = gemcitabine (1200 mg/m2) IV D1,8 q21 days; Dose level -1 = gemcitabine (1000 mg/m^2) IV D1,8 q21 days; Dose level -2 = gemcitabine (850 mg/m^2) IV D1,8 q21 days. The RP2D will be the dose level where 0-1 dose limiting toxicities (DLTs) in six patients occur.
TrastuzumabDrug
Also called Herceptin®
Trastuzumab will be given using an 8 mg/kg loading dose on cycle one, day one (C1D1), followed by 6 mg/kg IV on subsequent cycles every (q) 21 days.
PertuzumabDrug
Also called PERJETA®
Pertuzumab will be given using an 840 mg IV loading dose on C1D1, followed by 420 mg IV on subsequent cycles q 21 days.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation / Phase II Treatment | Experimental | Single arm, non-randomized, open label phase I/II multisite Simon two stage minimax trial. Gemcitabine plus trastuzumab and pertuzumab. Receives: Drug: Gemcitabine; Drug: Trastuzumab; Drug: Pertuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Recommended Phase II Dose (RP2D)
The RP2D dose in mg/m^2 of gemcitabine along with standard doses of pertuzumab (840 mg loading/420 mg maintenance) and Herceptin (8 mg/kg loading, 6 mg/kg maintenance). Safety data to be described using Common Terminology Criteria for Adverse Events (CTCAE) 4.0 terminology. Any participant who receives any dose of the study treatment will be evaluated for the safety/toxicity endpoints in the trial.
Measured: 6 Months
Phase II: Objective Response Rate (ORR)
Objective Response Rate: Response according to Response Evaluation in Solid Tumors (RECIST) 1.1 for the combination of gemcitabine+trastuzumab+pertuzumab at the recommended phase II dose. Complete Response (CR): Disappearance of all evidence of tumor for at least two cycles of therapy. Tumor markers must be normal. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking a reference the baseline sum longest diameter. Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the beginning of treatment or the appearance of one or more new lesions.
Measured: Up to 36 Months
Secondary outcomes (2)
Phase II: Progression Free Survival (PFS)
Median progression free survival (in months) for all participants evaluable for response. The time-to-event data will be summarized using Kaplan-Meir curve method for all patients who are evaluable for the ORR endpoint. Progressive disease (PD): At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the beginning of treatment or the appearance of one or more new lesions.
Measured: Up to 12 months
Overall Survival (OS)
Median overall survival (in months) for all participants evaluable for response. The length of time from the start of treatment that participants are still alive.
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2014 (estimated)
- Study start5 Sep 2014
- Primary completion24 Apr 2018
- Study completion16 Mar 2020
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 H. Lee Moffitt Cancer Center and Research InstituteThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Hatem Soliman, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02139358
- Sponsor's protocol ID
- MCC-17656
- Other IDs
- ML28939
- Status last verified
- Feb 2021
- First submitted
- 13 May 2014
- Last updated
- 4 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer
- ClinicalTrials.gov ID
- NCT02139358
- Acronym / sponsor ID
- MCC-17656
- Conditions
- Breast Cancer
- Keywords
- Breast - Female, Metastatic, HER2+
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 5 Sep 2014 (actual)
- Primary completion
- 24 Apr 2018 (actual)
- Study completion
- 16 Mar 2020 (actual)
- First posted
- 15 May 2014 (estimated)
- Results
- Posted 20 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and activity of gemcitabine plus trastuzumab and pertuzumab in patients with metastatic human epidermal growth factor receptor 2 (HER2)+ breast cancer who have progressed on at least one prior line of chemotherapy plus HER2 targeted agent such as T-DM1, trastuzumab, or lapatinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation / Phase II Treatment | Experimental | Drug: Gemcitabine, Drug: Trastuzumab, Drug: PertuzumabSingle arm, non-randomized, open label phase I/II multisite Simon two stage minimax trial. Gemcitabine plus trastuzumab and pertuzumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Adult males or females (aged 18 or older) with histologically confirmed, metastatic human epidermal growth factor receptor 2 (HER2)+ (by immunohistochemistry (IHC) 3+ or fluorescence in situ hydridization (FISH) ratio ≥ 2.0) breast cancer
- Have progressed on at least one prior line of chemotherapy plus HER2 directed therapy such as trastuzumab and/or pertuzumab in the metastatic setting. T-DM1 would count as a line of therapy and patients previously treated with T-DM1 are eligible.
- Have not been treated with gemcitabine in the metastatic setting
- Measurable disease per Response Evaluation in Solid Tumors (RECIST) 1.1 criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 2≤
Key exclusion criteria (10 listed)
- Active uncontrolled infection or major concurrent illness which in the opinion of the investigator would render the participant unsafe to proceed with the study
- Uncontrolled central nervous system (CNS) metastases. Treated, non-progressing CNS disease (documented by brain magnetic resonance imaging [MRI]) off corticosteroids for at least 1 month potential participants are eligible.
- Women who are pregnant or lactating
- Prior chemotherapy within the last 3 weeks (last 6 weeks for nitrosureas/mitomycin)
- Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation)
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 |
|---|---|---|
| GemcitabineAlso: GEMZAR®The Phase I trial will start at the recommended phase II dose (RP2D) for gemcitabine but will have a de-escalation dose levels in the event that an unacceptable toxicity requires dose reduction. Dose level 0 = gemcitabine (1200 mg/m2) IV D1,8 q21 days; Dose level -1 = gemcitabine (1000 mg/m^2) IV D1,8 q21 days; Dose level -2 = gemcitabine (850 mg/m^2) IV D1,8 q21 days. The RP2D will be the dose level where 0-1 dose limiting toxicities (DLTs) in six patients occur. | Drug | Dose Escalation / Phase II Treatment |
| TrastuzumabAlso: Herceptin®Trastuzumab will be given using an 8 mg/kg loading dose on cycle one, day one (C1D1), followed by 6 mg/kg IV on subsequent cycles every (q) 21 days. | Drug | Dose Escalation / Phase II Treatment |
| PertuzumabAlso: PERJETA®Pertuzumab will be given using an 840 mg IV loading dose on C1D1, followed by 420 mg IV on subsequent cycles q 21 days. | Drug | Dose Escalation / Phase II Treatment |
Primary outcome
Phase I: Recommended Phase II Dose (RP2D)
Time frame: 6 Months
The RP2D dose in mg/m^2 of gemcitabine along with standard doses of pertuzumab (840 mg loading/420 mg maintenance) and Herceptin (8 mg/kg loading, 6 mg/kg maintenance). Safety data to be described using Common Terminology Criteria for Adverse Events (CTCAE) 4.0 terminology. Any participant who receives any dose of the study treatment will be evaluated for the safety/toxicity endpoints in the trial.
Phase II: Objective Response Rate (ORR)
Time frame: Up to 36 Months
Objective Response Rate: Response according to Response Evaluation in Solid Tumors (RECIST) 1.1 for the combination of gemcitabine+trastuzumab+pertuzumab at the recommended phase II dose. Complete Response (CR): Disappearance of all evidence of tumor for at least two cycles of therapy. Tumor markers must be normal. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking a reference the baseline sum longest diameter. Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the beginning of treatment or the appearance of one or more new lesions.
2 secondary outcomes
Phase II: Progression Free Survival (PFS)
Time frame: Up to 12 months
Overall Survival (OS)
Time frame: Up to 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Moffitt Cancer Center Clinical Trials websiteLink provided by the sponsor.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
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.
Hatem Soliman, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Gemcitabine, Trastuzumab and Pertuzumab in people with Breast Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
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 11 inclusion and 10 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 4 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 20 Jul 2018). 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?
Phase I: Recommended Phase II Dose (RP2D) (time frame: 6 Months). The study lists 2 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 4 Feb 2021.