Chemotherapy Followed by Peripheral Stem Cell Transplantation Plus Biological Therapy in Treating Women With Stage IV Breast Cancer

NCT00020722 | Terminated Phase 2 Results DMC

• 4 other identifiers: CDR0000068707P30CA022453WSU-2007-033RWMC-0634246
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation plus biological therapy may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: This phase II trial is studying how well chemotherapy followed by peripheral stem cell transplantation plus biological therapy works in treating women with stage IV breast cancer.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; recurrent breast cancer

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival

  Length of time from day of transplant until recurrence or relapse.

Secondary Outcomes (1)

• Overall Survival

  Length of time from day of transplant until death.

Study Arms (1)

therapeutic autologous lymphocytes

EXPERIMENTAL

Biological: therapeutic autologous lymphocytes; Drug: Ifosfamide, carboplatin, and etoposide (ICE) regimen; Drug: Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC); Procedure: Leukapheresis; Procedure: peripheral blood stem cell transplantation (PBSCT)

Interventions

therapeutic autologous lymphocytes BIOLOGICAL

Immediately after pheresis, the lymphocytes will be activated with soluble monoclonal anti-CD3 antibody (OKT3) which cross-links the CD3 receptors on T cells and activates T cells. The time for ATC infusions will vary from patient to patient, but the infusion rate will be based on the rate calculated from the endotoxin level in the cell product. All patients will be observed for at least 1 hr after an infusion.

therapeutic autologous lymphocytes

Ifosfamide, carboplatin, and etoposide (ICE) regimen DRUG

Ifosfamide 2,500 mg/m2 given IV daily on day -8, -7, -6, -5, -4, and -3 prior to PBSCT. Ifosfamide 2,500 mg/m2 infused IV over 1 hour (hour 0-1) on days -8 to -3 for a total dose of 15,000 mg/m2. Mesna will be administered per BMT Standard of Care Guideline at a dose of 25% of the total Ifosfamide dose 30 minutes prior to and then 3, 6, and 9 hours after ifosfamide daily on days -8, -7, -6, -5, -4, and -3 prior to PBSCT for a total dose of 2500 mg/m2. Carboplatin at a dose of 250 mg/m2 will be given daily on days -8, -7, -6, -5, -4, and -3 prior to PBSCT for a total dose of 1500 mg/m2. VP-16 (etoposide) at a dose of 200 mg/m2 will be given IV on days -8, -7, -6, -5, -4 and -3. The total dose of VP-16 given prior to PBSCT will be 2,400 mg/m2. VP-16 will be given 200 mg/m2

Also known as: Ifex®, Paraplatin ®, Toposar®, VePesid®, Etopophos®, VP-16, Etoposide phosphate

therapeutic autologous lymphocytes

Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC) DRUG

Cyclophosphamide will be given at a dose of 2000 mg/m2 in NS IV over one hour daily on days -4, -3, and -2 (total = 6000 mg/m2). Thiotepa will be given at a dose of 167 mg/m2 in NS IV over one hour daily on days -4, -3, -2 (total = 500 mg/m2) as the preparative regimen followed by PBSCT on day 0. Carboplatin will be given at a dose of 267 mg/m2 in D5W IV over one hour daily on days -4, -3, and -2. Mesna will be administered per BMT Standard of Care Guidelines at a dose of 25% of the total cyclophosphamide dose 30 minutes prior to and then 3, 6, and 9 hours after cyclophosphamide daily on days -4, -3, and -2 prior to PBSCT for a total of 2000mg/m2.

Also known as: Cytoxan®, Neosar®, Paraplatin ®

therapeutic autologous lymphocytes

Leukapheresis PROCEDURE

Peripheral blood mononuclear cells (PBMC) will be collected by leukapheresis (for generation of ATC) prior to or post G-CSF (16 ug/kg/day) priming for collecting stem cells.

therapeutic autologous lymphocytes

peripheral blood stem cell transplantation (PBSCT) PROCEDURE

Will be collected either before or after peripheral blood stem cell collection for stem cell transplant.

therapeutic autologous lymphocytes

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Women with histologically documented metastatic carcinoma of the breast * Bilateral disease allowed * Concurrent intraductal or lobular carcinoma in situ allowed * Measurable or evaluable recurrent metastatic disease (stage IV) documented by radiograph, CT scan, nuclear medicine scan, or physical exam * Biopsy of recurrent site(s) recommended but not required * Nonmeasurable disease allowed if tumor or metastatic disease has been previously removed or successfully treated * 0 to 3+ HER2 amplification, as determined by FISH * No clinical evidence of active brain metastases * Patients with treated brain metastases (i.e., those who have received definitive radiation, chemotherapy, and/or underwent surgery) and are stable are eligible * Hormone receptor status: * Estrogen or progesterone receptor positive or negative PATIENT CHARACTERISTICS: * Menopausal status not specified * Karnofsky performance status 70-100% OR ECOG performance status 0-2 * Life expectancy at least 3 months * Granulocyte count at least 1,500/mm\^3 * Platelet count at least 50,000/mm\^3 * Hemoglobin greater than 8 g/dL * Bilirubin less than 1.5 times normal * AST, ALT, and alkaline phosphatase \< 5 times upper normal * Creatinine less than 1.8 mg/dL * Creatinine clearance at least 60 mL/min * BUN less than 1.5 times normal * No myocardial infarction (MI) within the past year * No history of MI (\> 1 year ago) with current coronary symptoms requiring medication * No current history of angina/coronary symptoms requiring medication * No clinical evidence of congestive heart failure requiring medical management * No significant congestive heart failure * No other uncontrolled or significant cardiovascular disease * Ejection fraction at least 45% at rest by MUGA * Systolic BP \< 130 mm Hg and diastolic BP \< 80 mm Hg * BP must be controlled to meet the standard by anti-hypertensive medications for at least 7 days prior to the first infusion * PFT-FEV\_1 at least 50% predicted * DLCO2 at least 50% predicted * FVC at least 50% predicted * No other malignancy within the past 3 years * No other serious medical or psychiatric illness that would preclude study participation * HIV negative * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Prior chemotherapy regimens allowed, including prior treatment on protocol WSU-2006-130 * Prior vaccine therapy on protocol WSU-2006-130 allowed * More than 4 weeks to leukapheresis since prior hormonal therapy * No radiation to the axial skeleton within 4 weeks of leukapheresis * No concurrent hormonal therapy for breast cancer * Hormones administered for non-disease-related condition (e.g. insulin for diabetes) allowed * Concurrent steroids for adrenal failure, septic shock, or pulmonary toxicity allowed

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

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ifosfamide; Carboplatin; Etoposide; Ice; Clinical Protocols; etoposide phosphate; Cyclophosphamide; Thiotepa; Leukapheresis; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Water; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Weather; Meteorological Concepts; Environment and Public Health; Therapeutics; Epidemiologic Study Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Triethylenephosphoramide; Aziridines; Azirines; Cytapheresis; Biological Therapy; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Transplantation; Surgical Procedures, Operative

Limitations and Caveats

Not enough funding to finish study, cost of immunotherapy infusions for the stem cell transplant portion \& of infusions for targeted T cell therapy were limited due to lack of funding, trial was converted into a proof-of-principle or concept trial.

Results Point of Contact

• Title: Lawrence G. Lum, M.D., D.Sc
• Organization: Barbara Ann Karmanos Cancer Institute

luml@karmanos.org

(313) 576-8326

Study Officials

• Lawrence G. Lum, MD, DSc

  Barbara Ann Karmanos Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 11, 2001
• First Posted: January 27, 2003
• Study Start: August 1, 2007
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: February 17, 2016
• Results First Posted: March 30, 2015

Record last verified: 2016-02

Locations

US (1)