Combination Chemotherapy and Trastuzumab in Treating Women With Metastatic Breast Cancer

October 4, 2019 updated by: Alliance for Clinical Trials in Oncology

Randomized Phase II Trial of Paclitaxel, Carboplatin and rhuMAb Her-2 (Herceptin) as First-Line Chemotherapy in Patients With Metastatic Breast Cancer Who Overexpress Her-2

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase II trial to study the effectiveness of combining paclitaxel, carboplatin, and trastuzumab in treating women who have metastatic breast cancer that overexpresses HER2.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the response rate associated with two different treatment schedules of paclitaxel, carboplatin, and trastuzumab (Herceptin) in women with overexpressed HER-2 growth factor receptor and metastatic breast cancer. (Schedule A closed to accrual effective 05/16/2003).
  • Compare the time to progression and median survival in patients treated with these schedules.
  • Compare the toxicity of these treatment schedules in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to prior adjuvant therapy (none vs less than 6 months vs at least 6 months), estrogen receptor (ER) status and progesterone receptor (PR) status at initial diagnosis (ER positive/PR positive or unknown vs ER positive/PR negative vs ER positive or unknown/PR negative), menopausal status (pre vs post), and performance status (0 or 1 vs 2). Patients are assigned to 1 of 2 treatment schedules.

  • Schedule A: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes and then trastuzumab (Herceptin) IV over 90 minutes on day 1 of week 1. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab IV over 30 minutes every 3 weeks until disease progression. (Schedule A closed to accrual effective 05/16/2003).
  • Schedule B: Patients receive paclitaxel IV over 1 hour followed by carboplatin IV over 15 minutes on day 1 of weeks 1-3 and trastuzumab IV over 90 minutes immediately after carboplatin on day 1. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab IV over 30 minutes every 3 weeks until disease progression.

Patients are followed every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 36-92 patients (18-46 per treatment schedule) will be accrued for this study within 7-18.5 months. (Schedule A closed to accrual effective 05/16/2003).

Study Type

Interventional

Enrollment (Actual)

92

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
        • Allan Blair Cancer Centre
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259-5404
        • CCOP - Scottsdale Oncology Program
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic
    • Illinois
      • Peoria, Illinois, United States, 61602
        • CCOP - Illinois Oncology Research Association
      • Urbana, Illinois, United States, 61801
        • CCOP - Carle Cancer Center
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
    • Iowa
      • Cedar Rapids, Iowa, United States, 52403-1206
        • CCOP - Cedar Rapids Oncology Project
      • Des Moines, Iowa, United States, 50309-1016
        • CCOP - Iowa Oncology Research Association
      • Sioux City, Iowa, United States, 51101-1733
        • Siouxland Hematology-Oncology
    • Kansas
      • Wichita, Kansas, United States, 67214-3882
        • CCOP - Wichita
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • CCOP - Ochsner
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • CCOP - Michigan Cancer Research Consortium
    • Minnesota
      • Duluth, Minnesota, United States, 55805
        • CCOP - Duluth
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
      • Saint Cloud, Minnesota, United States, 56303
        • CentraCare Health Plaza
      • Saint Louis Park, Minnesota, United States, 55416
        • CCOP - Metro-Minnesota
    • Nebraska
      • Omaha, Nebraska, United States, 68106
        • CCOP - Missouri Valley Cancer Consortium
    • North Dakota
      • Bismarck, North Dakota, United States, 58501-5505
        • Medcenter One Health System
      • Fargo, North Dakota, United States, 58122
        • CCOP - Merit Care Hospital
      • Grand Forks, North Dakota, United States, 58201
        • Altru Cancer Center
    • Ohio
      • Toledo, Ohio, United States, 43623-3456
        • CCOP - Toledo Community Hospital
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822-2001
        • CCOP - Geisinger Clinic and Medical Center
    • South Dakota
      • Rapid City, South Dakota, United States, 57709
        • Rapid City Regional Hospital
      • Sioux Falls, South Dakota, United States, 57104
        • CCOP - Sioux Community Cancer Consortium
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54301
        • CCOP - St. Vincent Hospital Cancer Center, Green Bay

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed metastatic adenocarcinoma of the breast

  • Strong overexpression of HER-2 by immunohistochemistry (3+)

    • 0-2+ tumors allowed if demonstrate amplification by FISH
  • Bidimensionally measurable disease
  • Brain metastasis must not represent sole site of disease
  • No untreated brain metastasis receiving radiotherapy
  • Previously treated brain metastases in continued response to radiotherapy and/or surgery for at least 2 months allowed

  • Hormone receptor status:

    • Positive or negative

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Sex:

  • Female

Menopausal status:

  • Not specified

Performance status:

  • ECOG 0-2

Life expectancy:

  • At least 3 months

Hematopoietic:

  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 1.5 mg/dL
  • AST no greater than 3 times upper limit of normal (ULN) (5 times ULN if liver metastases present)

Renal:

  • Creatinine no greater than 1.5 times ULN

Cardiovascular:

  • No myocardial infarction within the past 6 months
  • No congestive heart failure or unstable angina
  • No clinically significant pericardial effusion or arrhythmia

Other:

  • No other invasive malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No active uncontrolled infection
  • No prior allergic reaction to Cremophor EL, anesthetics, or muscle relaxants
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No concurrent filgrastim (G-CSF)

Chemotherapy:

  • Prior adjuvant chemotherapy allowed
  • Prior taxane therapy allowed
  • No prior cisplatin or carboplatin
  • No prior chemotherapy for metastatic disease

Endocrine therapy:

  • Not specified

Radiotherapy:

  • See Disease Characteristics
  • No prior radiotherapy to more than 25% of marrow
  • At least 4 weeks since prior radiotherapy
  • No concurrent radiotherapy

Surgery:

  • See Disease Characteristics
  • At least 4 weeks since prior surgery and recovered

Other:

  • At least 7 days since prior parenteral antibiotics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Schedule A: paclitaxel + carboplatin + trastuzumab

Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes and then trastuzumab (Herceptin) IV over 90 minutes on day 1 of week 1. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab IV over 30 minutes every 3 weeks until disease progression.

Patients are followed every 3 months for 2 years and then every 6 months thereafter.
Drug: carboplatin
Drug: paclitaxel
Biological: trastuzumab
Experimental: Schedule B: paclitaxel + carboplatin + trastuzumab

Patients receive paclitaxel IV over 1 hour followed by carboplatin IV over 15 minutes on day 1 of weeks 1-3 and trastuzumab IV over 90 minutes immediately after carboplatin on day 1. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab IV over 30 minutes every 3 weeks until disease progression.

Patients are followed every 3 months for 2 years and then every 6 months thereafter.
Drug: carboplatin
Drug: paclitaxel
Biological: trastuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
response rate
Time Frame: Up to 5 years
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
time to progression
Time Frame: Up to 5 years
Up to 5 years
median survival
Time Frame: Up to 5 years
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 1999

Primary Completion (Actual)

December 1, 2005

Study Completion (Actual)

March 15, 2019

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

October 8, 2019

Last Update Submitted That Met QC Criteria

October 4, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCCTG-983252
  • CDR0000066689 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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