Combination Chemotherapy With Trastuzumab in Treating Women With Metastatic Breast Cancer

NCT00036868 | Completed Phase 2

• 4 other identifiers: EORTC-10995-16999EORTC-10995EORTC-16999IDBBC-EORTC-10995
• Study Type: interventional
• Target: 90
• Locations: 9 countries
• Sites: 13

Brief 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.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; recurrent breast cancer

Outcome Measures

Primary Outcomes (2)

• Clinical heart failure rate measured by New York Heart Association classification, LVEF, and ECG

  from registration

• Response rate by RECIST

  from registration

Secondary Outcomes (3)

• Duration of response by RECIST

  from registration

• Time to progression

  from registration

• Toxicity measured by CTC v2.0

  from registration

Study Arms (1)

CMF + Herceptin

EXPERIMENTAL

Biological: trastuzumab; Drug: CMF regimen; Drug: cyclophosphamide; Drug: fluorouracil; Drug: methotrexate

Interventions

trastuzumab BIOLOGICAL

CMF + Herceptin

CMF regimen DRUG

CMF + Herceptin

cyclophosphamide DRUG

CMF + Herceptin

fluorouracil DRUG

CMF + Herceptin

methotrexate DRUG

CMF + Herceptin

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (13)

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, 2020, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, B-2650, Belgium

Location

Herlev Hospital - University Hospital of Copenhagen

Copenhagen, DK-2730, Denmark

Location

National Cancer Institute of Egypt

Cairo, Egypt

Location

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, 21079, France

Location

Onze Lieve Vrouwe Gasthuis

Amsterdam, 1091 HA, Netherlands

Location

Leiden University Medical Center

Leiden, 2300 CA, Netherlands

Location

Nijmegen Cancer Center at Radboud University Medical Center

Nijmegen, NL-6500 HB, Netherlands

Location

Medical University of Gdansk

Gdansk, 80-211, Poland

Location

Institute of Oncology and Radiology of Serbia

Belgrade, 11000, Serbia

Location

Medical Oncology Centre of Rosebank

Johannesburg, 2193, South Africa

Location

Western Infirmary

Glasgow, Scotland, G11 6NT, United Kingdom

Location

Related Publications (2)

• 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.

  RESULT

• Tryfonidis K, Marreaud S, Khaled H, De Valk B, Vermorken J, Welnicka-Jaskiewicz M, Aalders K, Bartlett JMS, Biganzoli L, Bogaerts J, Cameron D; EORTC- Breast Cancer Group. Cardiac safety, efficacy, and correlation of serial serum HER2-extracellular domain shed antigen measurement with the outcome of the combined trastuzumab plus CMF in women with HER2-positive metastatic breast cancer: results from the EORTC 10995 phase II study. Breast Cancer Res Treat. 2017 Jun;163(3):507-515. doi: 10.1007/s10549-017-4203-y. Epub 2017 Mar 21.

  PMID: 28324265 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; CMF regimen; Cyclophosphamide; Fluorouracil; Methotrexate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• David Cameron

  Western General Hospital, Edinburgh

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2002
• First Posted: January 27, 2003
• Study Start: February 1, 2002
• Primary Completion: June 1, 2009
• Study Completion: February 1, 2010
• Last Updated: March 8, 2024

Record last verified: 2024-03

Locations

SE (1); EG (1); NL (3); FR (1); ZA (1); DK (1); BE (3); PL (1); GB (1)