Combination Chemotherapy Followed By Peripheral Stem Cell Transplantation in Treating Women With Breast Cancer (CTC)

A Phase II Study of Cyclophosphamide, Thiotepa, and Carboplatin (CTC) as a Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation in Patients With Breast Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by peripheral stem cell transplantation in treating women who have breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Cyclophosphamide; Drug: Thiotepa

Detailed Description

OBJECTIVES: I. Determine long term remission rates as measured by disease free survival in women with breast cancer treated with cyclophosphamide, thiotepa, and carboplatin followed by autologous hematopoietic stem cell transplantation. II. Determine the safety and efficacy of this combination chemotherapy regimen in this patient population.

OUTLINE: Peripheral blood stem cells (PBSC) are collected. Patients sequentially receive cyclophosphamide IV over 1 hour, thiotepa IV over 1 hour, and carboplatin IV over 1 hour on days -6 to -4. PBSC are reinfused on day 0. Patients are followed at 3 months, 6 months, 1 year, and then annually thereafter.

PROJECTED ACCRUAL: At least 40 patients with 4-9 positive lymph nodes and at least 50 patients with 10 positive lymph nodes will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32114
      • Halifax Medical Center
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 64 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS: Histologically confirmed breast cancer Stage II with greater than 3 positive axillary lymph nodes following standard induction chemotherapy, as well as surgery and/or radiation as clinically indicated Stage III following standard induction chemotherapy with an anthracycline based regimen, and surgery and/or radiation as clinically indicated Inflammatory carcinoma following standard induction chemotherapy with an anthracycline based regimen, and surgery and/or radiation as clinically indicated Stage IV metastatic disease that has demonstrated a complete response to an anthracycline containing regimen, or no evidence of disease after surgery or radiation Hormone receptor status: Not specified

PATIENT CHARACTERISTICS: Age: 64 and under Sex: Female Menopausal status: Not specified Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT/SGPT no greater than 2.5 times upper limit of normal No history of severe hepatic dysfunction Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: No evidence of severe cardiac dysfunction Ejection fraction at least 50% by MUGA No major heart disease Essential hypertension controlled with medications allowed Pulmonary: DLCO at least 50% of normal No symptomatic obstructive or restrictive pulmonary disease Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No psychosocial disorder that would preclude study compliance No concurrent active infections No insulin dependent diabetes mellitus No uncompensated major thyroid or adrenal dysfunction No significant skin breakdown from tumor or other disease HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics Prior total dose of doxorubicin or daunorubicin less than 450 mg/m2 unless endometrial biopsy shows less than grade 2 drug effect Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics Surgery: See Disease Characteristics Other: No concurrent nitroglycerin preparations for angina pectoris No concurrent antiarrhythmic drugs for major ventricular dysrrhythmias

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: CTC Conditioning Regimen; Cyclophosphamide Thiotepa Carboplatin

Drug: Carboplatin; Carboplatin will be given at a dose of 267 mg/m2 in D5 W IV over one hour daily on days -6, -5, and -4. (Total dose 800 mg/m2); Other Names: Paraplatin(R); Drug: Cyclophosphamide; Cyclophosphamide will be given at a dose of 2000 mg/m2 in NS IV over one hour daily on days -6, -5, and -4. (Total dose 6000 mg/m2); Drug: Thiotepa; Thiotepa will be given at a dose of 167 mg/m2 in NS IV over one hour daily on days -6, -5, and -4. (Total dose 500 mg/m2 )

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
relapse-free survival	relapse free survival determined by the Kaplan-Meier product-limit method	five years post transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Grade III/IV toxicities	rate of grade III/IV toxicity	five years post transplant

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Claudio Anasetti, MD, Moffitt Cancer Center

Study record dates

Study Major Dates

• Study Start: July 1, 1995
• Primary Completion (Actual): August 1, 2001
• Study Completion (Actual): July 1, 2007

Study Registration Dates

• First Submitted: June 2, 2000
• First Submitted That Met QC Criteria: April 1, 2004
• First Posted (Estimate): April 2, 2004

Study Record Updates

• Last Update Posted (Estimate): October 26, 2012
• Last Update Submitted That Met QC Criteria: October 24, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: stage IV breast cancer; stage IIIA breast cancer; recurrent breast cancer; stage IIIB breast cancer; stage II breast cancer; inflammatory breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Carboplatin; Thiotepa
• Other Study ID Numbers: MCC-11072; IRB-3898 (Other Identifier: University of South Florida); NCI-G00-1760 (Other Identifier: NCI)