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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00182793
• Other study ID #: 05042
• Secondary ID: P30CA033572CDR00
• Status: Completed
• Phase: Phase 2
• First received: September 15, 2005
• Last updated: October 9, 2014
• Start date: July 2005
• Est. completion date: October 2014

Study information

• Verified date: October 2014
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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:
• 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
• melphalan
Cycle 1: 150 mg/m2 on day -1 from PBSC reinfusion
• 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.
• 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:
• 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.

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to relapse and/or progression		5 years post treatment	No
Primary	Overall survival		5 years post treatment	No
Primary	Response rate for stage IV breast cancer at year 5		5 years post treatment	No
Primary	Feasibility		5 years post treatment	No
Secondary	Assessment of tumor markers and biology		12 months post treatment	No