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

NCT00182793 | Completed Phase 2 Results DMC

• 3 other identifiers: 05042P30CA033572CDR0000442105
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 5-Year Relapse-free Survival Rate

  Estimated using the product-limit method of Kaplan and Meier. Relapse defined as appearance of any new lesions during or after protocol treatment. Whenever possible, relapses should be documented histologically.

  From time of initial PBPC rescue until death or disease recurrence (disease progression for patients with stage IV disease), whichever came first, up to 5 years post treatment

• 5-Year Overall Survival Rate

  Estimated using the product-limit method of Kaplan and Meier. Patients who were still alive were censored at the date of last follow-up

  From time of initial PBPC rescue until the date of death from any cause, assessed up to 5 years post treatment.

Study Arms (2)

Arm I

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.

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

Arm II

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.

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

Interventions

trastuzumab BIOLOGICAL

Cycle 1: 6 mg/kg on day -2 from PBSC reinfusion Cycle 2: 6 mg/kg on day -7 from PBSC reinfusion

Arm I

carboplatin DRUG

Cycle 2: 800 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion

Arm II

cyclophosphamide DRUG

Cycle 2: 6000 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion

Arm II

melphalan DRUG

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

Arm I

thiotepa DRUG

Cycle 2: 500 mg/m2/96 hours on days -7 to -3 from PBSC reinfusion

Arm II

adjuvant therapy PROCEDURE

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.

Arm I; Arm II

autologous-autologous tandem hematopoietic stem cell transplantation PROCEDURE

Tandem high-dose chemotherapy comprising melphalan, carboplatin, thiotepa, and cyclophosphamide with or without trastuzumab (Herceptin®) followed by autologous peripheral blood stem cell transplantation.

Arm I; Arm II

bone marrow ablation with stem cell support PROCEDURE

Tandem high-dose chemotherapy comprising melphalan, carboplatin, thiotepa, and cyclophosphamide with or without trastuzumab (Herceptin®) followed by autologous peripheral blood stem cell transplantation

Arm I; Arm II

radiation therapy RADIATION

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.

Arm I; Arm II

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Inflammatory Breast Neoplasms; Breast Neoplasms, Male; Carcinoma, Ductal, Breast; Carcinoma, Lobular

Interventions

Trastuzumab; Carboplatin; Cyclophosphamide; Melphalan; Thiotepa; Chemotherapy, Adjuvant; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Combined Modality Therapy; Therapeutics; Drug Therapy

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-359-8111

Study Officials

• George Somlo, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2005
• First Posted: September 16, 2005
• Study Start: July 1, 2005
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: February 23, 2017
• Results First Posted: February 23, 2017

Record last verified: 2017-01

Locations

US (1)