Combination Chemotherapy With or Without Trastuzumab Followed By an Autologous Stem Cell Transplant and Radiation Therapy in Treating Patients With Stage III or Stage IV Breast Cancer
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Cancer |
Biological: trastuzumab Drug: carboplatin Drug: cyclophosphamide Drug: melphalan Drug: thiotepa Procedure: adjuvant therapy Procedure: autologous-autologous tandem hematopoietic stem cell transplantation Procedure: bone marrow ablation with stem cell support Radiation: radiation therapy |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
- Time to relapse and/or progression [ Time Frame: 5 years post treatment ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: 5 years post treatment ] [ Designated as safety issue: No ]
- Response rate for stage IV breast cancer at year 5 [ Time Frame: 5 years post treatment ] [ Designated as safety issue: No ]
- Feasibility [ Time Frame: 5 years post treatment ] [ Designated as safety issue: No ]
- Assessment of tumor markers and biology [ Time Frame: 12 months post treatment ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 100 |
| Study Start Date: | July 2005 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I
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.
|
Biological: trastuzumab
Cycle 1: 6 mg/kg on day -2 from PBSC reinfusion Cycle 2: 6 mg/kg on day -7 from PBSC reinfusion
Drug: melphalan
Cycle 1: 150 mg/m2 on day -1 from PBSC reinfusion
Procedure: 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.
Procedure: 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.
Procedure: 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: 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: Arm II
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.
|
Drug: carboplatin
Cycle 2: 800 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion
Drug: cyclophosphamide
Cycle 2: 6000 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion
Drug: thiotepa
Cycle 2: 500 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion
Procedure: 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.
Procedure: 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.
Procedure: 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: 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. |
Detailed 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.
Eligibility| Ages Eligible for Study: | up to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, California | |
| City of Hope Comprehensive Cancer Center | |
| Duarte, California, United States, 91010-3000 | |
| Principal Investigator: | George Somlo, MD | City of Hope Medical Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | City of Hope Medical Center |
| ClinicalTrials.gov Identifier: | NCT00182793 History of Changes |
| Other Study ID Numbers: | 05042, P30CA033572, CDR0000442105 |
| Study First Received: | September 15, 2005 |
| Last Updated: | February 14, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by City of Hope Medical Center:
|
stage IIIB breast cancer stage IIIC breast cancer stage IV breast cancer inflammatory breast cancer male breast cancer recurrent breast cancer invasive ductal breast carcinoma with predominant intraductal component invasive ductal breast carcinoma |
medullary ductal breast carcinoma with lymphocytic infiltrate mucinous ductal breast carcinoma Paget disease of the breast with invasive ductal carcinoma papillary ductal breast carcinoma tubular ductal breast carcinoma invasive lobular breast carcinoma with predominant in situ component invasive lobular breast carcinoma comedo ductal breast carcinoma |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Cyclophosphamide Melphalan Thiotepa Trastuzumab Carboplatin Immunosuppressive Agents |
Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists |
ClinicalTrials.gov processed this record on May 22, 2013