Breast Cancer
Conditions
Keywords
MAB 2C4 (PERTUZUMAB), MAB HER 2 (HERCEPTIN) (TRASTUZUMAB), TAXOL (PACLITAXEL), 10-142, Stage IV HER2 (+) breast cancer
Brief summary
The purpose of this study is to see if a combination of drugs can help to treat this type of cancer. One drug is a chemotherapy agent called paclitaxel (Taxol®). Paclitaxel will be given every week through the vein. Although the weekly schedule of paclitaxel is not included in the label, the schedule and dose of weekly paclitaxel have been studied and have been proven to be more effective than an old standard schedule. The other two work against HER2. One is called trastuzumab (Herceptin®) and it is commonly given to women with early HER2 positive breast cancer or with advanced HER2 positive breast cancer that has spread to other parts of the body. Trastuzumab will be given through the vein every 3 weeks (or every week at the doctor's discretion). The third drug, pertuzumab, is an investigational drug. It has not been approved by the Food and Drug Administration. It has been given in studies to over 800 people. It has been effective in treating HER2 positive breast cancer. Pertuzumab will be given every 3 weeks through the vein. This study is looking at the effectiveness of these three drugs together.
Interventions
DRUGpertuzumab in combination with trastuzumab and paclitaxel
The regimen will consist of paclitaxel (80 mg/m2) weekly + trastuzumab every 3 weeks (8 mg/kg loading dose → 6 mg/kg every 3 weeks) + pertuzumab every 3 weeks (840 mg as a loading dose → 420 mg), all given intravenously (IV). Patients may be given trastuzumab weekly in lieu of every 3 weeks (4 mg/kg loading dose → 2 mg/kg every 3 weeks). Patients will be on treatment until progression of disease.
Sponsors
Genentech, Inc.
University of Pennsylvania
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 * Stage IV HER2 (+) breast cancer. * Histologically documented HER2 (+) breast cancer as defined as IHC 3+ or FISH amplification of ≥ 2.0 of primary or metastatic site; results from the local lab are acceptable. (Optional tumor sample collection from primary or metastatic site may be obtained for HER2 testing at MSKCC). * ECOG performance 0 -1 (Appendix A) * 0-1 prior treatment in the metastatic setting (ie: hormone, chemotherapy, biologic, targeted agents). Prior anthracycline, paclitaxel, and trastuzumab in the adjuvant setting are allowed. If the patient has one trastuzumab-based treatment in the metastatic setting and is given a break (even intermittently) from the partner drug given with trastuzumab and is continued on trastuzumab alone, this would still be considered as one treatment. For example, if the patient was given paclitaxel + trastuzumab and was later continued on trastuzumab alone or then restarted on paclitaxel + trastuzumab (at the physician's discretion for any reason), the regimen paclitaxel + trastuzumab followed by trastuzumab alone (or followed by paclitaxel + trastuzumab again) may be considered as one treatment. * Measurable or non-measurable disease. Measurable lesions are defined as those that can be measured accurately in at least one diameter, that is 20 mm using conventional imaging techniques (including incremental CT) or 10 mm using spiral CT equipment and a lymph node 15 mm along the short axis. Non-measurable lesions are all other lesions, including small lesions (longest diameter \<10mm pathological a lymph nodes with 10 to less than 15mm along the short axis, bony metastases, leptomeningeal disease, ascites, pleural/pericardial effusions, inflammatory breast cancer, lymphangitis carcinomatosis, and heavily calcified and cystic/necrotic lesions. * LVEF ≥ 50% * Hematologic parameters: white blood cell (WBC) count of ≥ 3000/ul, absolute neutrophil count (ANC) ≥1500/ul, platelets ≥ 100,000/ul, hemoglobin ≥ 10.0 g/dl * Non-hematologic parameters: bilirubin ≤ 1.5 mg/dl, AST/ALT ≤ 2.5 x upper limit of normal (ULN), alkaline phosphatase ≤ 5 x ULN. * Creatinine ≤ 1.5 mg/dl * Patients with stable and treated brain lesions of a duration of ≥ 2 months may be enrolled.
Exclusion criteria
* History of prior cardiac morbidities within 12 months (unstable angina, myocardial infarction, CHF, uncontrolled ventricular arrhythmias) * Prior pertuzumab * History of prior ≥ G 3 hypersensitivity (HSR) or any toxicity to trastuzumab that warranted permanent cessation of this antibody * History of prior ≥ G 3 HSR or any toxicity to paclitaxel warranted permanent cessation of this chemotherapy * \> G 2 peripheral neuropathy * Patients with a history of chronic hepatitis B or C should be excluded from the study as paclitaxel is potentially hepatotoxic * Pregnant patients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Are Progression Free at 6 Months or Later. | 6 months | Patients who are considered progression-free at 6 months are deemed successes. Failures are those patients who progressed before the 6 month mark. 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 non-target lesion, or the appearance of new lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants by Response Rate Using the RECIST Criteria (Version 1.1) | every 4th cycle CT of chest and abdomen +/- pelvis up to 24 months | Extent of disease evaluation will consist of a CT of chest and abdomen +/- pelvis. Bone scan and PET are optional. Every 4th cycle, this can be done within +/- 2 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR., |
| Number of Participants Evaluated for Cardiac Safety | baseline and every 4th cycle of treatment up to 24 months | We will also assess the LVEF at baseline and after every 4th cycle of treatment with an ECHO with a strain imaging analysis. When an ECHO cannot be done, a MUGA scan may be done.Patients who have surpassed the 6 month period may complete ECHO with strain imaging analysis or MUGA every 6 months +/- 1 month starting from the most recent ECHO scan date. This study will use the NCI Common Toxicity Criteria (CTC) AE version 4.0 for toxicity. |
| Number of Participants Evaluated With Toxicity | 2 years | This study will use the NCI Common Toxicity Criteria (CTC) AE version 4.0 for toxicity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pertuzumab in Combination With Trastuzumab and Paclitaxel This is a phase II study of pertuzumab in combination with trastuzumab and paclitaxel for the treatment of patients with Stage IV HER2 (+) breast cancer. | 70 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Pertuzumab in Combination With Trastuzumab and Paclitaxel |
|---|---|
| Age, Continuous | 52 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 43 Participants |
| Region of Enrollment United States | 70 Participants |
| Sex: Female, Male Female | 70 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 36 / 70 |
| other Total, other adverse events | 67 / 70 |
| serious Total, serious adverse events | 18 / 70 |
Outcome results
Primary
Percentage of Patients Who Are Progression Free at 6 Months or Later.
Patients who are considered progression-free at 6 months are deemed successes. Failures are those patients who progressed before the 6 month mark. 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 non-target lesion, or the appearance of new lesions
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pertuzumab in Combination With Trastuzumab and Paclitaxel | Percentage of Patients Who Are Progression Free at 6 Months or Later. | 86 percentage of partcipants |
Secondary
Number of Participants by Response Rate Using the RECIST Criteria (Version 1.1)
Extent of disease evaluation will consist of a CT of chest and abdomen +/- pelvis. Bone scan and PET are optional. Every 4th cycle, this can be done within +/- 2 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.,
Time frame: every 4th cycle CT of chest and abdomen +/- pelvis up to 24 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pertuzumab in Combination With Trastuzumab and Paclitaxel | Number of Participants by Response Rate Using the RECIST Criteria (Version 1.1) | Complete Response | 15 Participants |
| Pertuzumab in Combination With Trastuzumab and Paclitaxel | Number of Participants by Response Rate Using the RECIST Criteria (Version 1.1) | Partial Response | 27 Participants |
| Pertuzumab in Combination With Trastuzumab and Paclitaxel | Number of Participants by Response Rate Using the RECIST Criteria (Version 1.1) | Stable Disease | 17 Participants |
| Pertuzumab in Combination With Trastuzumab and Paclitaxel | Number of Participants by Response Rate Using the RECIST Criteria (Version 1.1) | Progression of Disease | 1 Participants |
| Pertuzumab in Combination With Trastuzumab and Paclitaxel | Number of Participants by Response Rate Using the RECIST Criteria (Version 1.1) | Not Evaulable | 10 Participants |
Secondary
Number of Participants Evaluated for Cardiac Safety
We will also assess the LVEF at baseline and after every 4th cycle of treatment with an ECHO with a strain imaging analysis. When an ECHO cannot be done, a MUGA scan may be done.Patients who have surpassed the 6 month period may complete ECHO with strain imaging analysis or MUGA every 6 months +/- 1 month starting from the most recent ECHO scan date. This study will use the NCI Common Toxicity Criteria (CTC) AE version 4.0 for toxicity.
Time frame: baseline and every 4th cycle of treatment up to 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pertuzumab in Combination With Trastuzumab and Paclitaxel | Number of Participants Evaluated for Cardiac Safety | 70 Participants |
Secondary
Number of Participants Evaluated With Toxicity
This study will use the NCI Common Toxicity Criteria (CTC) AE version 4.0 for toxicity.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pertuzumab in Combination With Trastuzumab and Paclitaxel | Number of Participants Evaluated With Toxicity | 70 Participants |