Overview

This trial is active, not recruiting.

Condition breast cancer
Treatments trastuzumab, carboplatin, cyclophosphamide, melphalan, thiotepa, adjuvant therapy, autologous-autologous tandem hematopoietic stem cell transplantation, bone marrow ablation with stem cell support, radiation therapy
Phase phase 2
Target HER2
Sponsor City of Hope Medical Center
Collaborator National Cancer Institute (NCI)
Start date July 2005
End date January 2015
Trial size 100 participants
Trial identifier NCT00182793, 05042, CDR0000442105, P30CA033572

Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. An autologous stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy with or without trastuzumab followed by an autologous stem cell transplant and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy with or without trastuzumab followed by an autologous stem cell transplant and radiation therapy works in treating patients with stage III or stage IV breast cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients undergo stem cell collection. Patients receive high-dose melphalan IV with or without trastuzumab (Herceptin®). One day later, patients undergo autologous peripheral blood stem cell (PBSC) transplantation. No more than 7 weeks later, patients proceed to course 2. After recover from high-dose chemotherapy and autologous PBSC transplantation, patients with stage IIIB or IIIC disease undergo radiotherapy to the chest wall and lymph nodes. Patients with stage IV disease undergo radiotherapy using helical tomotherapy or standard radiotherapy to oligometastatic sites.
trastuzumab
Cycle 1: 6 mg/kg on day -2 from PBSC reinfusion Cycle 2: 6 mg/kg on day -7 from PBSC reinfusion
melphalan
Cycle 1: 150 mg/m2 on day -1 from PBSC reinfusion
adjuvant therapy
Tandem high-dose chemotherapy comprising melphalan, carboplatin, thiotepa, and cyclophosphamide with or without trastuzumab (Herceptin®) followed by autologous peripheral blood stem cell transplantation and helical tomotherapy or loco-regional radiotherapy.
autologous-autologous tandem hematopoietic stem cell transplantation
Tandem high-dose chemotherapy comprising melphalan, carboplatin, thiotepa, and cyclophosphamide with or without trastuzumab (Herceptin®) followed by autologous peripheral blood stem cell transplantation.
bone marrow ablation with stem cell support
Tandem high-dose chemotherapy comprising melphalan, carboplatin, thiotepa, and cyclophosphamide with or without trastuzumab (Herceptin®) followed by autologous peripheral blood stem cell transplantation
radiation therapy
After recovery from high-dose chemotherapy and autologous PBSC transplantation; patients with stage IIIB or IIIC disease undergo radiotherapy to the chest wall and lymph nodes. Treatment should be delivered daily M-F @ 180-200 cGY/day to a total of 4,500 to 5,040 cGy. Patients with stage IV disease undergo radiotherapy using helical tomotherapy or standard radiotherapy to oligometastatic sites. Treatment should be delivered daily @180-220 cGY/day to a total of 4,000-5,000 cGy.
(Experimental)
Patients undergo stem cell collection. Patients receive high-dose carboplatin, thiotepa, and cyclophosphamide IV continuously over 4 days followed by autologous PBSC transplantation. After recover from high-dose chemotherapy and autologous PBSC transplantation, patients with stage IIIB or IIIC disease undergo radiotherapy to the chest wall and lymph nodes. Patients with stage IV disease undergo radiotherapy using helical tomotherapy or standard radiotherapy to oligometastatic sites.
carboplatin
Cycle 2: 800 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion
cyclophosphamide
Cycle 2: 6000 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion
thiotepa
Cycle 2: 500 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion
adjuvant therapy
Tandem high-dose chemotherapy comprising melphalan, carboplatin, thiotepa, and cyclophosphamide with or without trastuzumab (Herceptin®) followed by autologous peripheral blood stem cell transplantation and helical tomotherapy or loco-regional radiotherapy.
autologous-autologous tandem hematopoietic stem cell transplantation
Tandem high-dose chemotherapy comprising melphalan, carboplatin, thiotepa, and cyclophosphamide with or without trastuzumab (Herceptin®) followed by autologous peripheral blood stem cell transplantation.
bone marrow ablation with stem cell support
Tandem high-dose chemotherapy comprising melphalan, carboplatin, thiotepa, and cyclophosphamide with or without trastuzumab (Herceptin®) followed by autologous peripheral blood stem cell transplantation
radiation therapy
After recovery from high-dose chemotherapy and autologous PBSC transplantation; patients with stage IIIB or IIIC disease undergo radiotherapy to the chest wall and lymph nodes. Treatment should be delivered daily M-F @ 180-200 cGY/day to a total of 4,500 to 5,040 cGy. Patients with stage IV disease undergo radiotherapy using helical tomotherapy or standard radiotherapy to oligometastatic sites. Treatment should be delivered daily @180-220 cGY/day to a total of 4,000-5,000 cGy.

Primary Outcomes

Measure
Time to relapse and/or progression
time frame: 5 years post treatment
Overall survival
time frame: 5 years post treatment
Response rate for stage IV breast cancer at year 5
time frame: 5 years post treatment
Feasibility
time frame: 5 years post treatment

Secondary Outcomes

Measure
Assessment of tumor markers and biology
time frame: 12 months post treatment

Eligibility Criteria

Male or female participants up to 65 years old.

DISEASE CHARACTERISTICS: - Histologically confirmed breast cancer, meeting 1 of the following stage criteria: - Stage IIIB or IIIC disease, meeting both of the following criteria: - Must have received prior neoadjuvant or adjuvant therapy - Must have undergone lumpectomy or mastectomy - Stage IV disease, meeting all of the following criteria: - Only 1-3 organ sites with disease involvement after induction chemotherapy - Achieved at least a partial response after induction chemotherapy - No more than 3 lesions in the organ sites combined - Inflammatory breast cancer allowed - Completed chemotherapy, surgery, or radiotherapy for breast cancer within the past 6 months - Hormone receptor status: - Not specified PATIENT CHARACTERISTICS: Age - 65 and under Sex - Male or female Menopausal status - Not specified Performance status - Karnofsky 80-100% Life expectancy - Not specified Hematopoietic - Absolute neutrophil count ≥ 1,000/mm^3 - Platelet count ≥ 100,000/mm^3 Hepatic - SGOT or SGPT ≤ 2 times upper limit of normal - Bilirubin ≤ 1.5 mg/dL Renal - Creatinine ≤ 1.2 mg/dL - Creatinine clearance ≥ 70 mL/min Cardiovascular - LVEF ≥ 55% by MUGA or echocardiogram Pulmonary - FEV_1 ≥ 60% of predicted - DLCO ≥ 60% of the lower limit of predicted value - Oxygen saturation > 92% on room air Other - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - No autoimmune disorders - No immunosuppressive condition - No other malignancy within the past 5 years PRIOR CONCURRENT THERAPY: Biologic therapy - No prior biologic therapy except trastuzumab (Herceptin®) Chemotherapy - See Disease Characteristics Endocrine therapy - Not specified Radiotherapy - See Disease Characteristics - No prior radiotherapy to adjacent or involved sites of disease that would preclude study radiotherapy Surgery - See Disease Characteristics Other - No other concurrent anticancer therapy

Additional Information

Official title Phase II Study of Tandem Cycle Dose-Intense Chemotherapy of Melphalan and Carboplatin, Thiotepa and Cyclophosphamide (STMP V) ± Trastuzumab Followed by Helical Tomotherapy or Local Regional Radiation Therapy for Stage IV Metastatic and Stage IIIB/C Breast Cancer
Principal investigator George Somlo, MD
Description OBJECTIVES: - Determine the feasibility of tandem high-dose chemotherapy comprising melphalan, carboplatin, thiotepa, and cyclophosphamide with or without trastuzumab (Herceptin®) followed by autologous peripheral blood stem cell transplantation and helical tomotherapy or loco-regional radiotherapy in patients with high-risk stage IIIB, IIIC, or IV breast cancer. - Determine the toxic effects of this regimen in these patients. OUTLINE: Patients undergo stem cell collection. - Course 1: Patients receive high-dose melphalan IV with or without trastuzumab (Herceptin®). One day later, patients undergo autologous peripheral blood stem cell (PBSC) transplantation. No more than 7 weeks later, patients proceed to course 2. - Course 2: Patients receive high-dose carboplatin, thiotepa, and cyclophosphamide IV continuously over 4 days followed by autologous PBSC transplantation. After recover from high-dose chemotherapy and autologous PBSC transplantation, patients with stage IIIB or IIIC disease undergo radiotherapy to the chest wall and lymph nodes. Patients with stage IV disease undergo radiotherapy using helical tomotherapy or standard radiotherapy to oligometastatic sites. PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.
Trial information was received from ClinicalTrials.gov and was last updated in July 2014.
Information provided to ClinicalTrials.gov by City of Hope Medical Center.