Combination Chemotherapy With Trastuzumab in Treating Women With Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Randomized Phase II Study Of CMF Alone And In Combination With Anti c-erbB2 Antibody (Herceptin) In Women With c-erbB2 Positive Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00036868
• Other study ID #: EORTC-10995-16999
• Secondary ID: EORTC-10995EORTC
• Status: Completed
• Phase: Phase 2
• Start date: February 2002
• Est. completion date: February 2010

Study information

• Verified date: March 2024
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy such as cyclophosphamide, methotrexate, and fluorouracil use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy with trastuzumab may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining combination chemotherapy with trastuzumab in treating women who have metastatic breast cancer.

Description:

OBJECTIVES: - Compare the incidence of clinical heart failure in women with c-erbB2-positive metastatic breast cancer treated with cyclophosphamide, methotrexate, and fluorouracil in combination with trastuzumab (Herceptin®). - Compare the therapeutic activity of this regimen, in terms of objective response rate, in these patients. - Compare the duration of response and time to progression in patients treated with this regimen. - Compare the toxic effects of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive CMF comprising cyclophosphamide orally on days 1-14 or IV on days 1 and 8 and methotrexate IV and fluorouracil IV on days 1 and 8. Patients also receive trastuzumab (Herceptin®) IV over 30-90 minutes once weekly beginning on day 1. Treatment repeats every 4 weeks for 8 courses. Patients then receive trastuzumab once every 3 weeks in the absence of disease progression, unacceptable toxicity, or patient refusal. Patients are followed every 8 weeks until documentation of disease progression or initiation of a new anticancer therapy. Patients developing disease progression are followed every 12 weeks. PROJECTED ACCRUAL: A total of 66 patients will be accrued for this study within 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: February 2010
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic breast cancer c-erbB2 positive (3+ overexpression by the HercepTest™ method) in the primary tumor or metastatic site
• At least 1 unidimensionally measurable target lesion
• At least 20 mm by conventional techniques OR
• At least 10 mm by spiral CT scan
• Lesions that have been irradiated in the preceding 3 months cannot be used as target lesions unless they have appeared or clearly progressed since prior irradiation
• No bone lesions as the only target lesions
• No contralateral breast cancer that is c-erbB2-positive or c-erbB2-negative/unknown, with status determined on a metastatic site
• No CNS metastases
• CT scan of brain and CSF cytology are required if neurologic symptoms are present
• Hormone receptor status:
• Any estrogen or progesterone receptor status PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Any status

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.25 times upper limit of normal (ULN)
• Transaminases less than 2.5 times ULN (5 times ULN if liver metastases present)

Renal:

• For patients age 18 to 69:
• Creatinine no greater than ULN
• For patients age 70 and over:
• Creatinine clearance normal

Cardiovascular:

• LVEF normal by MUGA or echocardiogram
• No clinical heart failure

Pulmonary:

• No malignancy-associated dyspnea at rest
• No requirement for supportive oxygen therapy

Other:

• Not pregnant or nursing
• No other prior or concurrent malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or basal cell skin cancer
• No psychological, familial, sociological, or geographical condition that would preclude compliance with study therapy and follow-up schedule PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior anti-c-erbB2 antibody, including trastuzumab (Herceptin®)
• No other concurrent biologic therapy

Chemotherapy:

• No more than 1 prior chemotherapy regimen for metastatic breast cancer
• Prior combination of cyclophosphamide, methotrexate, and fluorouracil (CMF) allowed in the adjuvant or metastatic setting only if the disease-free interval after completion of CMF was at least 12 months
• Prior anthracyclines and/or taxanes allowed
• At least 4 weeks since prior anthracyclines
• No prior cumulative dose of doxorubicin more than 360 mg/m^2
• No prior cumulative dose of epirubicin more than 720 mg/m^2
• No prior cumulative dose of mitoxantrone more than 90 mg/m^2
• No other concurrent chemotherapy

Endocrine therapy:

• More than 2 weeks since prior hormonal therapy in the adjuvant or metastatic setting
• No concurrent hormonal therapy

Radiotherapy:

• See Disease Characteristics
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• No other concurrent anticancer therapy or investigational drugs
• No concurrent bisphosphonates started after study enrollment except for hypercalcemia

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• trastuzumab

Drug:
• CMF regimen

• cyclophosphamide

• fluorouracil

• methotrexate

Locations

Country	Name	City	State
Belgium	Ziekenhuis Netwerk Antwerpen Middelheim	Antwerp
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Denmark	Herlev Hospital - University Hospital of Copenhagen	Copenhagen
Egypt	National Cancer Institute of Egypt	Cairo
France	Centre de Lutte Contre le Cancer Georges-Francois Leclerc	Dijon
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Nijmegen Cancer Center at Radboud University Medical Center	Nijmegen
Poland	Medical University of Gdansk	Gdansk
Serbia	Institute of Oncology and Radiology of Serbia	Belgrade
South Africa	Medical Oncology Centre of Rosebank	Johannesburg
United Kingdom	Western Infirmary	Glasgow	Scotland

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  Denmark,  Egypt,  France,  Netherlands,  Poland,  Serbia,  South Africa,  United Kingdom, 

References & Publications (1)

Neskovic-Konstantinovic Z, Nooij M, Khaled H, et al.: Safety and efficacy of combined trastuzumab and CMF therapy in women with metastatic breast cancer: EORTC protocol 10995. [Abstract] J Clin Oncol 25 (Suppl 18): A-1040, 2007.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical heart failure rate measured by New York Heart Association classification, LVEF, and ECG		from registration
Primary	Response rate by RECIST		from registration
Secondary	Duration of response by RECIST		from registration
Secondary	Time to progression		from registration
Secondary	Toxicity measured by CTC v2.0		from registration