Cyclophosphamide and Vaccine Therapy With or Without Trastuzumab in Treating Patients With Metastatic Breast Cancer

NCT00971737 | Completed Phase 2 Results

• 6 other identifiers: J0947P30CA006973JHOC-J0947NA_00024527GENENTECH-JHOC-J0947CDR0000653173
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an effective immune response to kill tumor cells. Biological therapies, such as cyclophosphamide and trastuzumab, may increase the number of immune cells and make the immune response stronger. It is not yet known whether giving cyclophosphamide together with vaccine therapy is more effective with or without trastuzumab in treating patients with metastatic breast cancer. PURPOSE: This randomized phase II trial is studying the side effects of giving cyclophosphamide together with vaccine therapy and to see how well it works compared with giving cyclophosphamide and vaccine therapy together with trastuzumab in treating patients with metastatic breast cancer.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; male breast cancer

Outcome Measures

Primary Outcomes (4)

• Toxicity as Assessed by Number of Grade 3 or 4 Adverse Events

  Number of grade 3 or 4 nonhematologic toxicity (except alopecia), or any grade 4 hematologic toxicity as defined by NCI CTCAE v3.0

  3 years

• Clinical Benefit (CB) as Assessed by Progression Free Survival at Six Months

  Progression-free survival is measured as percentage of participants with stable disease or complete response, as defined by RECIST criteria, six months after receiving last vaccination. Progressive disease (PD) will be defined by the appearance of a new lesion, or by an increase of at least 20% in the sum of the longest diameter of target lesions, taking as a reference that smallest sum longest diameter recorded since the study intervention began. In the case of bone lesions, progressive disease will be established after eight weeks of increasing or new lesions if there is subjective progressive disease as noted by increasing bone pain or decreasing performance status. These observations must be present for at least two measurement periods separated by at least four weeks.

  6 months post-intervention

• HER-2/Neu-specific Immune Responses as Measured by Number of Participants With Positive for Delayed-type Hypersensitivity (DTH) Response

  3 years

• Pharmacodynamics of Peripheral CD4+CD25+ Regulatory T Cells

  3 years

Secondary Outcomes (3)

• Immune Priming in In-vivo Vaccine-site Biopsies

  3 years

• Enumeration of CD8+ T Cells Specific for hTERT by ELISPOT

  3 years

• Characterization of the T-cell Memory Pool Pre- and Post-vaccination

  3 years

Study Arms (2)

Cyclophosphamide and Vaccine only

ACTIVE COMPARATOR

Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.

Biological: allogeneic GM-CSF-secreting breast cancer vaccine; Drug: cyclophosphamide

Cyclophosphamide, Vaccine and Trastuzumab

EXPERIMENTAL

Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.

Biological: allogeneic GM-CSF-secreting breast cancer vaccine; Biological: trastuzumab; Drug: cyclophosphamide

Interventions

allogeneic GM-CSF-secreting breast cancer vaccine BIOLOGICAL

Given intradermally

Cyclophosphamide and Vaccine only; Cyclophosphamide, Vaccine and Trastuzumab

trastuzumab BIOLOGICAL

Given IV

Cyclophosphamide, Vaccine and Trastuzumab

cyclophosphamide DRUG

Given IV

Cyclophosphamide and Vaccine only; Cyclophosphamide, Vaccine and Trastuzumab

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the breast * Does not overexpress HER-2/neu, defined as FISH negative or 0, 1+, or 2+ by IHC * Stage IV disease * Must not be eligible for therapy of known curative potential for metastatic breast cancer * Measurable or evaluable disease * Stable CNS disease allowed provided that it's adequately treated and not under active treatment * Hormone receptor status not specified PATIENT CHARACTERISTICS: * Menopausal status not specified * ECOG performance status 0-1 * ANC \> 1,000/mm\^3 * Platelets \> 100,000/mm\^3 * Serum bilirubin \< 2.0 mg/dL (unless due to Gilbert syndrome) * AST and ALT \< 2 times upper limit of normal (ULN) * Alkaline phosphatase \< 5 times ULN * Serum creatinine \< 2.0 mg/dL * Ejection fraction normal by MUGA OR ≥ 50% by echocardiogram * Not pregnant or nursing * Fertile patients must use effective contraception * HIV negative * Asthma or chronic obstructive pulmonary disease that does not require daily systemic corticosteroids allowed * No prior or concurrent autoimmune disease requiring management with systemic immunosuppression, including any of the following: * Inflammatory bowel disease * Systemic vasculitis * Scleroderma * Psoriasis * Multiple sclerosis * Hemolytic anemia or immune-mediated thrombocytopenia * Rheumatoid arthritis * Systemic lupus erythematosus * Sjogren syndrome * Sarcoidosis * Other rheumatologic disease * No other malignancies within the past 5 years, except carcinoma in situ of the cervix, superficial nonmelanoma skin cancer, superficial bladder cancer, or tamoxifen-related endometrial cancer that has been adequately treated * No active major medical or psychosocial problems that could be complicated by study participation * No symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest * No uncontrolled medical problems * No evidence of active acute or chronic infection * No known severe hypersensitivity to trastuzumab, except mild to moderate infusion reactions that are easily managed and do not recur * No allergy to corn PRIOR CONCURRENT THERAPY: * See Disease Characteristics * More than 28 days since prior and no other concurrent chemotherapy, radiation therapy, or biologic therapy (except trastuzumab) * Concurrent endocrine therapy and supportive therapy with bisphosphonates allowed * More than 28 days since prior and no other concurrent participation in an investigational new drug trial * More than 28 days since prior and no other concurrent systemic oral steroids * Topical, ocular, and nasal steroids allowed * No prior vaccination with the allogeneic GM-CSF-secreting breast tumor vaccine

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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male

Interventions

Trastuzumab; Cyclophosphamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Leisha Emens, MD, PhD
• Organization: Johns Hopkins University

emensle@jhmi.edu

Study Officials

• Leisha A. Emens, MD, PhD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: September 3, 2009
• First Posted: September 4, 2009
• Study Start: July 1, 2009
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: April 24, 2019
• Results First Posted: March 12, 2019

Record last verified: 2019-04

Locations

US (1)