Breast CancerPhase 2NCT00444587
A Study of Herceptin (Trastuzumab) in Combination With 2nd-Line Chemotherapy in Patients With HER2 Positive Metastatic Breast Cancer.
A Phase 2 study testing Second line chemotherapy and trastuzumab [Herceptin] in people with Breast Cancer, run by Hoffmann-La Roche at 30 sites in 8 countries.
Trial summary
This 2 arm study will compare the efficacy and safety of continuation or discontinuation of Herceptin treatment in combination with 2nd line chemotherapy, in patients with HER2 positive metastatic breast cancer whose condition has progressed on 1st line chemotherapy plus Herceptin. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Second line chemotherapy and trastuzumab [Herceptin]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 30 sitesin 8 countries
- Study dates
- Mar 2007to Aug 2011
- Phase
- Phase 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- female patients, >= 18 years of age;
- metastatic breast cancer;
- HER2 overexpression (IHC 3+ and/or FISH positive);
- disease progression during or after previous 1st line chemotherapy + Herceptin;
- scheduled to receive 2nd line chemotherapy.
Who cannot join
- concurrent immunotherapy or hormonal therapy;
- anthracyclines as part of previous 1st line chemotherapy or planned 2nd line chemotherapy;
- cardiac toxicity during previous 1st line chemotherapy + Herceptin;
- history of other malignancy within last 5 years.
Trial locations and contacts
30 sites in 8 countries.
30 sites in 8 countries
Hungary13 sites
Study site
Budapest, 1082
Study site
Budapest, 1115
Study site
Budapest, 1122
Study site
Budapest, 1125
Study site
Budapest, 1135
Study site
Budapest, 1145
Study site
Debrecen, 4032
Study site
Győr, 9023
Study site
Gyula, 5700
Study site
Nyíregyháza, 4400
Study site
Szeged, 6725
Study site
Székesfehérvár, 8000
Study site
Szombathely, 9700
Israel8 sites
Study site
Haifa, 31096
Study site
Holon, 58100
Study site
Petah Tikva, 49100
Study site
Ramat Gan, 52621
Study site
Rehovot, 76100
Study site
Safed, 13110
Study site
Tel Aviv, 6423906
Study site
Tsrifin, 70300
Turkey (Türkiye)2 sites
Study site
Adana, 01330
Study site
Ankara, 06590
About this study
Official title: A Multicenter Phase II Trial of Trastuzumab (Herceptin) Continuation in Combination With 2nd-line Chemotherapies After Progression on a 1st-line Chemotherapy Combined With Trastuzumab in Patients With HER2 Positive Metastatic Breast Cancer (Treatment Beyond Progression, TBP)
This 2 arm study will compare the efficacy and safety of continuation or discontinuation of Herceptin treatment in combination with 2nd line chemotherapy, in patients with HER2 positive metastatic breast cancer whose condition has progressed on 1st line chemotherapy plus Herceptin. Patients will be randomized either to continue or discontinue Herceptin treatment (6mg/kg iv infusion every 3 weeks) while receiving second-line chemotherapy of the investigator's choice. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.
- Conditions
- Breast Cancer
- Being tested
- Second line chemotherapy, trastuzumab [Herceptin]
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Second line chemotherapyDrug
As prescribed
trastuzumab [Herceptin]Drug
6mg/kg iv every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Experimental | Not described Receives: Drug: Second line chemotherapy; Drug: trastuzumab [Herceptin] |
| Only Chemotherapy | Active comparator | Not described Receives: Drug: Second line chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Time to Disease Progression
Time to disease progression (TTP) in days was defined as the time from enrollment to objective disease progression (all categories other than objective disease progression was set to be censored including death before progression). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions. Tumor assessments were performed using computer tomography or magnetic resonance imaging. TTP as assessed by investigator, along with a recalculation done by computer algorithm is presented below. Median time was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Measured: Up to 5 years
Secondary outcomes (14)
Objective Response Rate
Objective response rate (ORR) is defined as the percentage of participants with tumor shrinkage of a predefined amount. It is a combination of complete response (CR) and partial response (PR) and was assessed according to the RECIST criteria 1.0. Complete response refers to the disappearance of all target lesions and all non-target non-measurable lesions. Partial Response refers to an at least 30 percent decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter. Objective response rate was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Measured: Up to 5 years
Clinical Benefit Rate
Clinical benefit rate (CBR) was defined as the percentage of participants taking a benefit from the treatments. CBR includes 1) Complete response (CR): disappearance of all target lesions and all non-target non-measurable lesions 2) Partial response (PR) : >=30% decrease in the sum of the longest diameter of target lesions and 3) Stable disease (SD): non-PR and non-progressive disease. It was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and assessed by CT or MRI by the investigator. CBR was also assessed by computer. Clinical benefit rate was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Measured: Up to 5 years
Median Time to Treatment Failure
Time to treatment failure is defined as a composite endpoint measuring time (number of days) from enrollment to discontinuation of treatment or change in treatment for any reason, including disease progression, treatment toxicity and death. Median time to treatment failure was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Measured: Up to 5 years
Overall Survival
Overall Survival is defined as the time (number of days) between enrollment and the date of death due to any cause. Overall survival was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Measured: Up to 5 years
Number of Participants With Any Adverse Events and Serious Adverse Events
An adverse event (AE) is any untoward medical occurrence in a participant who is administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.
Measured: Up to 5 years
Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels
Participants in the study were evaluated for the serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkali phosphatase (ALP) at Visit 1 and final study assessments (Up to 5 years). Serum glutamic oxaloacetic transaminase, Serum glutamic-pyruvic transaminase and Alkali Phosphatase levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Measured: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study Assessments (Up to 5 years)
Biochemistry Safety Laboratory Parameters: Mean Total Bilirubin and Serum Creatinine Levels
Participants in the study were evaluated for the total bilirubin and serum creatinine. Total Bilirubin and serum creatinine levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Measured: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study Assessments (Up to 5 years)
Biochemistry Safety Laboratory Parameters: Mean Albumin Levels
Participants in the study were evaluated for the albumin at Visit 1 and Final study assessments. Albumin levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Measured: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study assessments (Up to 5 years)
Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels
Participants in the study were evaluated for the biochemical safety laboratory parameters urea, sodium and potassium. Urea, sodium and potassium levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Measured: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study assessments (Up to 5 years)
Hematology Safety Laboratory Parameters: Mean Hemoglobin Levels
Participants in the study were evaluated for the Hemoglobin up to 5 years. Hemoglobin levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Measured: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)
Hematology Safety Laboratory Parameters: Mean Total Leukocytes Counts
Participants in the study were evaluated for the total leukocytes up to 5 years. Total leukocytes counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Measured: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)
Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts
Participants in the study were evaluated for the Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes at Visit 1 and final study assessments.
Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Measured: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)
Hematology Safety Laboratory Parameter: Mean Platelets Counts
Participants in the study were evaluated for the platelets at Visit 1 and final study assessments. Platelet counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Measured: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)
Mean Left Ventricular Ejection Fraction
Left ventricular ejection fraction (LVEF) is a measure of the percent of blood ejected from the ventricle in one heartbeat. It is a measure of cardiac function and was assessed by echocardiogram or multigated angiogram at Visit 0 [Screening period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years).
Measured: Visit 0 [Screening period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2007 (estimated)
- Study startMar 2007
- Primary completionAug 2011
- Study completionAug 2011
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00444587
- Sponsor's protocol ID
- ML19944
- Status last verified
- May 2016
- First submitted
- 7 Mar 2007
- Last updated
- 21 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase II Trial of Trastuzumab (Herceptin) Continuation in Combination With 2nd-line Chemotherapies After Progression on a 1st-line Chemotherapy Combined With Trastuzumab in Patients With HER2 Positive Metastatic Breast Cancer (Treatment Beyond Progression, TBP)
- ClinicalTrials.gov ID
- NCT00444587
- Acronym / sponsor ID
- ML19944
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Mar 2007
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 8 Mar 2007 (estimated)
- Results
- Posted 21 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This 2 arm study will compare the efficacy and safety of continuation or discontinuation of Herceptin treatment in combination with 2nd line chemotherapy, in patients with HER2 positive metastatic breast cancer whose condition has progressed on 1st line chemotherapy plus Herceptin. Patients will be randomized either to continue or discontinue Herceptin treatment (6mg/kg iv infusion every 3 weeks) while receiving second-line chemotherapy of the investigator's choice. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Experimental | Drug: Second line chemotherapy, Drug: trastuzumab [Herceptin] |
| Only Chemotherapy | Active comparator | Drug: Second line chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- female patients, >= 18 years of age;
- metastatic breast cancer;
- HER2 overexpression (IHC 3+ and/or FISH positive);
- disease progression during or after previous 1st line chemotherapy + Herceptin;
- scheduled to receive 2nd line chemotherapy.
Key exclusion criteria (4 listed)
- concurrent immunotherapy or hormonal therapy;
- anthracyclines as part of previous 1st line chemotherapy or planned 2nd line chemotherapy;
- cardiac toxicity during previous 1st line chemotherapy + Herceptin;
- history of other malignancy within last 5 years.
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 |
|---|---|---|
| Second line chemotherapyAs prescribed | Drug | Only Chemotherapy, Trastuzumab + 2nd Line Chemotherapy |
| trastuzumab [Herceptin]6mg/kg iv every 3 weeks | Drug | Trastuzumab + 2nd Line Chemotherapy |
Primary outcome
Median Time to Disease Progression
Time frame: Up to 5 years
Time to disease progression (TTP) in days was defined as the time from enrollment to objective disease progression (all categories other than objective disease progression was set to be censored including death before progression). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions. Tumor assessments were performed using computer tomography or magnetic resonance imaging. TTP as assessed by investigator, along with a recalculation done by computer algorithm is presented below. Median time was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
14 secondary outcomes
Objective Response Rate
Time frame: Up to 5 years
Clinical Benefit Rate
Time frame: Up to 5 years
Median Time to Treatment Failure
Time frame: Up to 5 years
Overall Survival
Time frame: Up to 5 years
Number of Participants With Any Adverse Events and Serious Adverse Events
Time frame: Up to 5 years
Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study Assessments (Up to 5 years)
Biochemistry Safety Laboratory Parameters: Mean Total Bilirubin and Serum Creatinine Levels
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study Assessments (Up to 5 years)
Biochemistry Safety Laboratory Parameters: Mean Albumin Levels
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study assessments (Up to 5 years)
Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study assessments (Up to 5 years)
Hematology Safety Laboratory Parameters: Mean Hemoglobin Levels
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)
Hematology Safety Laboratory Parameters: Mean Total Leukocytes Counts
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)
Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)
Hematology Safety Laboratory Parameter: Mean Platelets Counts
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)
Mean Left Ventricular Ejection Fraction
Time frame: Visit 0 [Screening period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2016.
- 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.
Clinical Trials study director
Hoffmann-La Roche
30 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Second line chemotherapy and trastuzumab [Herceptin] in people with Breast Cancer, run by Hoffmann-La Roche at 30 sites in 8 countries.
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 5 inclusion and 4 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 21 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Hungary, Israel, Lithuania, Slovakia, Turkey (Türkiye) and 3 more countries. 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 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 21 Jun 2016). 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?
Median Time to Disease Progression (time frame: Up to 5 years). 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 21 Jun 2016.