BIG 02/98 Docetaxel - Breast Cancer

NCT00174655 | Completed Phase 3

• 1 other identifier: RP56976_PR_315
• Study Type: interventional
• Target: 2,887
• Locations: 19 countries
• Sites: 19

Brief Summary

Primary objectives:

• To compare Disease-Free Survival (DFS) of an adjuvant treatment with docetaxel given either sequentially or in combination with doxorubicin and followed by CMF to doxorubicin alone or in combination with cyclophosphamide and followed by CMF in operable breast cancer patients with positive axillary lymph nodes. Secondary objectives:
• To compare DFS of an adjuvant treatment with doxorubicin followed by docetaxel followed by CMF to doxorubicin followed by CMF in operable breast cancer patients with positive axillary lymph nodes
• To compare DFS of an adjuvant treatment with docetaxel in combination with doxorubicin followed by CMF to doxorubicin in combination with cyclophosphamide followed by CMF in operable breast cancer patients with positive axillary lymph nodes
• To compare DFS of an adjuvant treatment with doxorubicin followed by docetaxel followed by CMF to doxorubicin in combination with docetaxel followed by CMF in operable breast cancer patients with positive axillary lymph nodes, (sequential mono-chemotherapy versus polychemotherapy).
• To compare overall survival of treatment arms.
• To compare toxicity of treatment arms.
• To evaluate pathologic and molecular markers for predicting efficacy.
• Socioeconomic data will be collected in order to be able to perform a socioeconomic analysis by country, when needed.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

• DFS of docetaxel arms versus non toxanes arm (DFS: interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death for any cause whichever occurs first.

  810 events or median 5 year follow-up whichever occurs first

Secondary Outcomes (2)

• DFS sequential/combined arms

  810 events or median 5 year follow-up whichever occurs first

• Safety NCI common toxicity criteria

  from baseline to study end

Study Arms (4)

A1

ACTIVE COMPARATOR

Drug: doxorubicine + cyclophosphamide sequential

A2

ACTIVE COMPARATOR

Drug: doxorubicine + cyclophosphamide combined

B

EXPERIMENTAL

Drug: Doxorubicine + docetaxel sequential

C

EXPERIMENTAL

Drug: doxorubicine + docetaxel combined

Interventions

Doxorubicine + docetaxel sequential DRUG

doxorubicin 75 mg/m² i.v. day 1, q 21 days for 3 cycles, followed by docetaxel 100 mg/m² i.v., 1 hour infusion, day 1, q 21 days for 3 cycles, followed by CMF for 3 cycles

B

doxorubicine + cyclophosphamide sequential DRUG

doxorubicin 75 mg/m² i.v. day 1 q 21 days for 4 cycles, followed by CMF (C: cyclophosphamide 100 mg/m² orally days 1-14, M: methotrexate: 40 mg/m² i.v. days 1 and 8, FU; 5-fluorouracil: 600 mg/m²) i.v. days 1 and 8, q 28 days for 3 cycles

A1

doxorubicine + cyclophosphamide combined DRUG

doxorubicin 60 mg/m² i.v. + cyclophosphamide 600 mg/m² i.v., day 1, q 21 days for 4 cycles, followed by CMF for 3 cycles.

A2

doxorubicine + docetaxel combined DRUG

doxorubicin 50 mg/m² i.v. + docetaxel 75 mg/m² i.v. 1 hour infusion (1 hour after doxorubicin), day 1, q 21 days for 4 cycles, followed by CMF for 3 cycles.

C

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven breast cancer. Interval between definitive surgery that includes axillary lymph node dissection and registration must be less than 60 days. A representative sample of the primary tumor (either blocks or slides) must be sent to the operational office, for central pathology reviews, after patients randomization.
• Definitive surgical treatment must be either mastectomy or breast conserving surgery, with axillary lymph node dissection (not sampling) for operable breast cancer (clinical T1-3, N0-1, M0). Margins of resected specimen from definitive surgery must be histologically free of invasive adenocarcinoma and ductal carcinoma in situ (DCIS). Lobular carcinoma in-situ does not count as a positive margin. Patients with histologically-documented infiltration of the skin (pT4) will not be eligible. Patients who have a breast conserving procedure with a positive margin may become eligible if they subsequently undergo adequate resection or mastectomy with clear margins.
• Histologic examination of the tumor: invasive adenocarcinoma with at least one axillary lymph node (pN1) showing evidence of tumor among a minimum of eight resected lymph nodes. All nodes must be examined by the pathologist. The determination of ER (estrogen receptor) and PgR (progesterone receptor) is mandatory and results must be known by the end of chemotherapy in order to decide whether hormonal therapy is indicated (Biochemical or immunohistochemical methods required ; ER and/or PgR positivity should be in accordance with the policy in use at each participating center. Each center will specify its own policy).
• Karnofsky Performance status index \> or = 70 %.
• Normal cardiac function must be confirmed by LVEF (MUGA scan or echocardiography). The result must be above the lower limit of normal for the institution.
• Laboratory requirements: (within 14 days prior to registration)
• Hematology
• Neutrophils \> or = 2.0 x 109/L
• Platelets \> or =100 x 109/L
• Hemoglobin \> or = 10 g/dL
• Hepatic function
• Total bilirubin \< or = 1 UNL
• ASAT (SGOT) and ALAT (SGPT) \< or = 1.5 UNL
• Alkaline phosphatase \< or = 2.5 UNL
• Renal function

You may not qualify if:

• Prior systemic anticancer therapy for breast cancer (chemo-immuno-hormonotherapy).
• Prior radiation therapy for breast cancer.
• Pregnant, or lactating patients.
• Any locally advanced (clinical or pathological T4 and/or N2-known N3) or metastatic(M1) breast cancer.Patients with inoperable residual axillary nodal disease or with supraclavicular nodes.
• Pre-existing motor or sensory neurotoxicity of a severity ³ grade 2 by NCI criteria.
• Other serious illness or medical condition:
• congestive heart failure or unstable angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or high-risk uncontrolled arrhythmias
• history of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent
• active uncontrolled infection
• active peptic ulcer, unstable diabetes mellitus
• Past or current history of other neoplasms except for:
• curatively treated basal cell skin cancer
• adequately treated in situ carcinoma of the cervix
• past history of ipsilateral or past or current history of contralateral invasive breast carcinoma
• past or current history of contralateral ductal in situ breast carcinoma

Sponsors & Collaborators

• Sanofi: lead

Study Sites (21)

Sanofi-Aventis

Macquarie Park, Australia

Location

Sanofi-Aventis

Vienna, Austria

Location

Sanofi-Aventis

Diegem, Belgium

Location

Sanofi-Aventis

São Paulo, ao, Brazil

Location

Sanofi-Aventis

Providencia Santiago, Chile

Location

Sanofi-Aventis

Prague, Czechia

Location

Sanofi-Aventis

Hørsholm, Denmark

Location

Sanofi-Aventis

Berlin, Germany

Location

Sanofi-Aventis

Budapest, Hungary

Location

Sanofi-Aventis

Dublin, Ireland

Location

Sanofi-Aventis

Netanya, Israel

Location

Sanofi-Aventis

Milan, Italy

Location

Sanofi-Aventis

Auckland, New Zealand

Location

Sanofi-Aventis

Porto Salvo, Portugal

Location

Sanofi-Aventis

Bratislava, Slovakia

Location

Sanofi-Aventis

Ljubljana, Slovenia

Location

Sanofi-Aventis

Gauteng, South Africa

Location

Sanofi-Aventis

Barcelona, Spain

Location

Sanofi-Aventis

Bromma, Sweden

Location

Sanofi-Aventis

Geneva, Switzerland

Location

Sanofi-Aventis

Guildford Surrey, United Kingdom

Location

Related Publications (2)

• Desmedt C, Fornili M, Clatot F, Demicheli R, De Bortoli D, Di Leo A, Viale G, de Azambuja E, Crown J, Francis PA, Sotiriou C, Piccart M, Biganzoli E. Differential Benefit of Adjuvant Docetaxel-Based Chemotherapy in Patients With Early Breast Cancer According to Baseline Body Mass Index. J Clin Oncol. 2020 Sep 1;38(25):2883-2891. doi: 10.1200/JCO.19.01771. Epub 2020 Jul 2.

  PMID: 32614702 DERIVED

• Fernandez-Cuesta L, Oakman C, Falagan-Lotsch P, Smoth KS, Quinaux E, Buyse M, Dolci MS, Azambuja ED, Hainaut P, Dell'orto P, Larsimont D, Francis PA, Crown J, Piccart-Gebhart M, Viale G, Leo AD, Olivier M. Prognostic and predictive value of TP53 mutations in node-positive breast cancer patients treated with anthracycline- or anthracycline/taxane-based adjuvant therapy: results from the BIG 02-98 phase III trial. Breast Cancer Res. 2012 May 2;14(3):R70. doi: 10.1186/bcr3179.

  PMID: 22551440 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Jean-Philippe Aussel

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 15, 2005
• Study Start: June 1, 1998
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: November 10, 2011

Record last verified: 2011-11

Locations

PT (1); IT (1); ES (1); BR (1); NZ (1); SE (1); ZA (1); DE (1); CL (1); HU (1); SL (1); CZ (1); AU (1); DK (1); CH (1); BE (1); GB (1); IE (1); IL (1)