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: July 10, 2014
Last verified: July 2014

September 15, 2005
July 10, 2014
July 2005
January 2015   (final data collection date for primary outcome measure)
  • 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 ]
Not Provided
Complete list of historical versions of study NCT00182793 on ClinicalTrials.gov Archive Site
Assessment of tumor markers and biology [ Time Frame: 12 months post treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
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
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

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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
  • 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
  • Drug: cyclophosphamide
    Cycle 2: 6000 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion
  • Drug: melphalan
    Cycle 1: 150 mg/m2 on day -1 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.

  • 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.
    Interventions:
    • Biological: trastuzumab
    • Drug: melphalan
    • Procedure: adjuvant therapy
    • Procedure: autologous-autologous tandem hematopoietic stem cell transplantation
    • Procedure: bone marrow ablation with stem cell support
    • Radiation: radiation therapy
  • 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.
    Interventions:
    • Drug: carboplatin
    • Drug: cyclophosphamide
    • Drug: thiotepa
    • Procedure: adjuvant therapy
    • Procedure: autologous-autologous tandem hematopoietic stem cell transplantation
    • Procedure: bone marrow ablation with stem cell support
    • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
100
Not Provided
January 2015   (final data collection date for primary outcome measure)

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
Both
up to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00182793
05042, P30CA033572, CDR0000442105
Yes
City of Hope Medical Center
City of Hope Medical Center
National Cancer Institute (NCI)
Principal Investigator: George Somlo, MD City of Hope Medical Center
City of Hope Medical Center
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP