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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00182793
First received: September 15, 2005
Last updated: January 24, 2014
Last verified: January 2014
  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

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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: January 2015 (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
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00182793

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
Investigators
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: January 24, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
Paget disease of the breast with invasive ductal carcinoma
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
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 Diseases
Skin Diseases
Breast Neoplasms
Neoplasms by Site
Neoplasms
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 April 16, 2014