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

• ClinicalTrials.gov Identifier: NCT01276041
• Recruitment Status: Completed
• First Posted: January 13, 2011
• Results First Posted: August 3, 2020
• Last Update Posted: August 3, 2020
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Genentech, Inc.; University of Pennsylvania
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: pertuzumab in combination with trastuzumab and paclitaxel	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 70 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Paclitaxel, Trastuzumab, and Pertuzumab in the Treatment of Metastatic HER2-Positive Breast Cancer
• Actual Study Start Date: January 5, 2011
• Actual Primary Completion Date: August 7, 2019
• Actual Study Completion Date: August 7, 2019

Arms and Interventions

Arm

Intervention/treatment

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.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Patients Who Are Progression Free at 6 Months or Later. [ Time Frame: 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 Outcome Measures :

1. Number of Participants by Response Rate Using the RECIST Criteria (Version 1.1) [ Time Frame: 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.",
2. Number of Participants Evaluated for Cardiac Safety [ Time Frame: 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.
3. Number of Participants Evaluated With Toxicity [ Time Frame: 2 years ]
   This study will use the NCI Common Toxicity Criteria (CTC) AE version 4.0 for toxicity.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, New Jersey

Memorial Sloan Kettering at Basking Ridge

Basking Ridge, New Jersey, United States, 07920

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States, 07748

United States, New York

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, United States, 11725

Memorial Sloan Kettering West Harrison

Harrison, New York, United States, 10604

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

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Genentech, Inc.

University of Pennsylvania

Investigators

• Principal Investigator: Chau Dang, MD; Memorial Sloan Kettering Cancer Center

  Study Documents (Full-Text)

Documents provided by Memorial Sloan Kettering Cancer Center:

Study Protocol and Statistical Analysis Plan  [PDF] January 10, 2018

More Information

Additional Information:

Memorial Sloan Kettering Cancer Center 

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT01276041
• Other Study ID Numbers: 10-142
• First Posted: January 13, 2011
• Results First Posted: August 3, 2020
• Last Update Posted: August 3, 2020
• Last Verified: August 2019

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; Pertuzumab; Skin Diseases; Paclitaxel; Trastuzumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological