Paclitaxel, Doxorubicin, and Cyclophosphamide With Or Without Carboplatin in Treating Women With Locally Advanced Breast Cancer That Can Be Removed by Surgery

NCT00589238 | Terminated Phase 2

• 2 other identifiers: CDR0000579522SINGAPORE-NCC-0701
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, doxorubicin, cyclophosphamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether combination chemotherapy is more effective with or without carboplatin in treating breast cancer. PURPOSE: This randomized phase II trial is studying giving paclitaxel together with doxorubicin and cyclophosphamide to see how well it works compared to giving paclitaxel together with doxorubicin, cyclophosphamide, and carboplatin in treating women with locally advanced breast cancer that can be removed by surgery.

Conditions

Breast Cancer

Keywords

stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate

  Pathological response will be assessed by evaluation of surgical specimen after completion of protocol treatment.

Secondary Outcomes (4)

• Clinical and pathological overall response rates

  Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.

• Overall and disease-free survival

  Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.

• Incidence of each toxicity item

  Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.

• Correlation between low BRCA1 expression (protein and mRNA), p53 mutation, positive CK5/6, positive CK14, basal like gene expression profile, and response to carboplatin based treatment

  Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.

Study Arms (2)

Arm 1 (Standard Arm)

OTHER

Arm 1 (Standard Arm) Preoperative (primary/ neoadjuvant) intravenous weekly paclitaxel 80 mg/m2 for 12 weeks followed by doxorubicin 60 mg/m2 in combination with cyclophosphamide 600 mg/m2 every 21 days for 4 cycles.

Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel

Arm 2 (Experimental Arm)

EXPERIMENTAL

Arm 2 (Experimental Arm) Preoperative intravenous weekly paclitaxel 80 mg/m2 in combination with carboplatin AUC 2 on D1, D8 and D15 every 28 days for 4 cycles followed by doxorubicin 60 mg/m2 in combination with cyclophosphamide 600 mg/m2 every 21 days for 4 cycles.

Drug: carboplatin; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel

Interventions

carboplatin DRUG

Arm 2 (Experimental Arm)

cyclophosphamide DRUG

Arm 1 (Standard Arm); Arm 2 (Experimental Arm)

doxorubicin hydrochloride DRUG

Arm 1 (Standard Arm); Arm 2 (Experimental Arm)

paclitaxel DRUG

Arm 1 (Standard Arm); Arm 2 (Experimental Arm)

Eligibility Criteria

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

You may qualify if:

• Female
• Menopausal status not specified
• ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
• Life expectancy \> 10 years
• Leukocytes ≥ 3,000/μL
• Absolute neutrophil count ≥ 1,500/μL
• Platelets ≥ 100,000/μL
• Total bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Cardiac ejection fraction ≥ 50% as assessed by MUGA scan or 2D echocardiogram

You may not qualify if:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel, carboplatin, or other agents used in the study
• Pre-existing peripheral neuropathy
• Uncontrolled intercurrent illness including, but not limited to, any of the following:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness or social situations that would limit compliance with study requirements
• Prior malignancies except for basal cell carcinoma of the skin or curatively treated carcinoma in situ of the cervix
• PRIOR CONCURRENT THERAPY:
• No prior chemotherapy or radiotherapy
• No HIV-positive patients receiving combination antiretroviral therapy
• No concurrent primary growth factor prophylaxis
• No other concurrent investigational agents
• No other concurrent chemotherapy, immunotherapy, hormonal cancer therapy, surgery for cancer, or experimental medications

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead

Study Sites (2)

National Cancer Centre - Singapore

Singapore, 169610, Singapore

Location

KK Women's and Children Hospital

Singapore, Singapore

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Carboplatin; Cyclophosphamide; Doxorubicin; Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• Wong Nan Soon, MBBS, MRCP, FAMS

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

• Ann Lee Siew Gek

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant

Study Record Dates

• First Submitted: January 3, 2008
• First Posted: January 9, 2008
• Study Start: January 1, 2008
• Primary Completion: July 1, 2012
• Last Updated: June 19, 2013

Record last verified: 2013-06

Locations

SG (2)