Clinical trial NCT01276041: Paclitaxel, Trastuzumab, and Pertuzumab in the Treatment of Metastatic HER2-Positive Breast Cancer
Official title: Paclitaxel, Trastuzumab, and Pertuzumab in the Treatment of Metastatic HER2-Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: MAB 2C4 (PERTUZUMAB)
MAB HER 2 (HERCEPTIN) (TRASTUZUMAB)
TAXOL (PACLITAXEL)
10-142
Stage IV HER2 (+) breast cancer
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: University of Pennsylvania
First posted: 2011-01-13
Enrollment: 70
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Patients Who Are Progression Free at 6 Months or Later.
timeFrame: 6 months
Secondary outcomes:
measure: Number of Participants by Response Rate Using the RECIST Criteria (Version 1.1)
timeFrame: every 4th cycle CT of chest and abdomen +/- pelvis up to 24 months
measure: Number of Participants Evaluated for Cardiac Safety
timeFrame: baseline and every 4th cycle of treatment up to 24 months
measure: Number of Participants Evaluated With Toxicity
timeFrame: 2 years
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering at Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center @ Suffolk
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering West Harrison
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering at Mercy Medical Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Chau Dang, MD
role: PRINCIPAL_INVESTIGATOR
References: