Combination Chemotherapy and Trastuzumab in Treating Women With Metastatic Breast Cancer

NCT ID: NCT00003612

Last Updated: 2019-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-04-30
• Study Completion Date: 2019-03-15

Brief Summary

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.

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).

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

trastuzumab

Intervention Type: BIOLOGICAL

carboplatin

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

trastuzumab

Intervention Type: BIOLOGICAL

carboplatin

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

Interventions

trastuzumab

Intervention Type: BIOLOGICAL

carboplatin

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edith A. Perez, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

CCOP - Scottsdale Oncology Program

Scottsdale, Arizona, United States

Mayo Clinic

Jacksonville, Florida, United States

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

Carle Cancer Center

Urbana, Illinois, United States

CCOP - Carle Cancer Center

Urbana, Illinois, United States

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, United States

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

Siouxland Hematology-Oncology

Sioux City, Iowa, United States

CCOP - Wichita

Wichita, Kansas, United States

CCOP - Ochsner

New Orleans, Louisiana, United States

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States

CCOP - Duluth

Duluth, Minnesota, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

CentraCare Health Plaza

Saint Cloud, Minnesota, United States

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Medcenter One Health System

Bismarck, North Dakota, United States

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

Altru Cancer Center

Grand Forks, North Dakota, United States

CCOP - Toledo Community Hospital

Toledo, Ohio, United States

CCOP - Geisinger Clinic and Medical Center

Danville, Pennsylvania, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, United States

CCOP - St. Vincent Hospital Cancer Center, Green Bay

Green Bay, Wisconsin, United States

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Countries

United States; Canada

References

Perez EA, Suman VJ, Rowland KM, Ingle JN, Salim M, Loprinzi CL, Flynn PJ, Mailliard JA, Kardinal CG, Krook JE, Thrower AR, Visscher DW, Jenkins RB. Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer. 2005 Dec;6(5):425-32. doi: 10.3816/CBC.2005.n.047.

Reference Type: RESULT

PMID: 16381626 (View on PubMed)

Perez EA, Rowland KM, Suman VJ, et al.: N98-32-52: efficacy and tolerability of two schedules of paclitaxel, carboplatin and trastuzumab in women with HER2 positive metastatic breast cancer: a North Central Cancer Treatment Group randomized phase II trial. [Abstract] Breast Cancer Res Treat 82 (Suppl 1): A-216, S47, 2003.

Reference Type: RESULT

Rowland KM, Suman VJ, Ingle JN, et al.: NCCTG 98-32-52: randomized phase II trial of weekly versus every 3-week administration of paclitaxel, carboplatin and trastuzumab in women with HER2 positive metastatic breast cancer (MBC). [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-31, 2003.

Reference Type: RESULT

Chumsri S, Sperinde J, Liu H, Gligorov J, Spano JP, Antoine M, Moreno Aspitia A, Tan W, Winslow J, Petropoulos CJ, Chenna A, Bates M, Weidler JM, Huang W, Dueck A, Perez EA. High p95HER2/HER2 Ratio Associated With Poor Outcome in Trastuzumab-Treated HER2-Positive Metastatic Breast Cancer NCCTG N0337 and NCCTG 98-32-52 (Alliance). Clin Cancer Res. 2018 Jul 1;24(13):3053-3058. doi: 10.1158/1078-0432.CCR-17-1864. Epub 2018 Mar 12.

Reference Type: DERIVED

PMID: 29530935 (View on PubMed)

Other Identifiers

CDR0000066689

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCCTG-983252

Identifier Type: -

Identifier Source: org_study_id