Combination Chemotherapy and Trastuzumab in Treating Women With Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003612
• Other study ID #: NCCTG-983252
• Secondary ID: CDR0000066689
• Status: Completed
• Phase: Phase 2
• Start date: April 1999
• Est. completion date: March 15, 2019

Study information

• Verified date: October 2019
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: March 15, 2019
• Est. primary completion date: December 2005
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• trastuzumab

Drug:
• carboplatin

• paclitaxel

Locations

Country	Name	City	State
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Medcenter One Health System	Bismarck	North Dakota
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	CCOP - Geisinger Clinic and Medical Center	Danville	Pennsylvania
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	CCOP - Duluth	Duluth	Minnesota
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	Mayo Clinic	Jacksonville	Florida
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Rapid City Regional Hospital	Rapid City	South Dakota
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 - Scottsdale Oncology Program	Scottsdale	Arizona
United States	Siouxland Hematology-Oncology	Sioux City	Iowa
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Carle Cancer Center	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	CCOP - Wichita	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (3)

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

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 f — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	response rate		Up to 5 years
Secondary	time to progression		Up to 5 years
Secondary	median survival		Up to 5 years