Paclitaxel, Trastuzumab, and Pertuzumab in the Treatment of Metastatic HER2-Positive Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Genentech, Inc.
University of Pennsylvania
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01276041
First received: January 6, 2011
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: pertuzumab in combination with trastuzumab and paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Paclitaxel, Trastuzumab, and Pertuzumab in the Treatment of Metastatic HER2-Positive Breast Cancer

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • The proportion of patients who are progression free at 6 months or later. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Patients who are considered progression-free at 6 months are deemed successes. Failures are those patients who progressed before the 6 month mark.


Secondary Outcome Measures:
  • The secondary objectives will be response will include the response rate using the RECIST criteria (version 1.1) [ Time Frame: every 4th cycle CT of chest and abdomen +/- pelvis ] [ Designated as safety issue: No ]
    EOD 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.

  • The secondary objectives will be safety (including cardiac safety)Study blood will be collected serially for cardiac biomarker analysis (TnI, BNP, NRG-1ß) and banked for future studies. [ Time Frame: baseline and every 4th cycle of treatment ] [ Designated as safety issue: Yes ]
    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. This study will use the NCI Common Toxicity Criteria (CTC) AE version 4.0 for toxicity.

  • The secondary objectives will be tolerability. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    This study will use the NCI Common Toxicity Criteria (CTC) AE version 4.0 for toxicity.


Estimated Enrollment: 69
Study Start Date: January 2011
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: pertuzumab 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > or = to 18
  • Stage IV HER2 (+) breast cancer.
  • Histologically documented HER2 (+) breast cancer as defined as IHC 3+ or FISH amplification of > or = to 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 > or = to 50%
  • Hematologic parameters: white blood cell (WBC) count of > or = to 3000/ul, absolute neutrophil count (ANC) > or = to 1500/ul, platelets > or = to 100,000/ul, hemoglobin > or = to 10.0 g/dl
  • Non-hematologic parameters: bilirubin < than or = to 1.5 mg/dl, AST/ALT < than or = to 2.5 x upper limit of normal (ULN), alkaline phosphatase < than or = to 5 x ULN.
  • Creatinine < than or = to 1.5 mg/dl
  • Patients with stable and treated brain lesions of a duration of > or = to 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 > or = to G 3 hypersensitivity (HSR) or any toxicity to trastuzumab that warranted permanent cessation of this antibody
  • History of prior > or = to 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01276041

Locations
United States, New Jersey
Memorial Sloan-Kettering at Basking Ridge
Basking Ridge, New Jersey, United States, 07920
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk
Commack, New York, United States, 11725
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Memorial Sloan-Kettering at Mercy Medical Center
Rockville Centre, New York, United States
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center
Sleepy Hollow, New York, United States, 10591
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Genentech, Inc.
University of Pennsylvania
Investigators
Principal Investigator: Chau Dang, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01276041     History of Changes
Other Study ID Numbers: 10-142
Study First Received: January 6, 2011
Last Updated: September 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
MAB 2C4 (PERTUZUMAB)
MAB HER 2 (HERCEPTIN) (TRASTUZUMAB)
TAXOL (PACLITAXEL)
10-142
Stage IV HER2 (+) breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Trastuzumab
Pertuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 16, 2014