Vaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer

NCT00436254 | Completed Phase 1 DMC

• 3 other identifiers: 6532NCI-2010-00869RG1704001
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Vaccines may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving vaccine therapy together with sargramostim may be an effective treatment for breast cancer and ovarian cancer. PURPOSE: This phase I trial is studying the side effects and identifying the best dose of vaccine therapy when given together with sargramostim in treating patients with stage III-IV breast cancer or ovarian cancer.

Conditions

HER2-positive Breast Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor

Outcome Measures

Primary Outcomes (2)

• Safety as measured by NCI CTCAE v 3.0

  From baseline

• Immune response

  From baseline

Secondary Outcomes (2)

• Impact of dose on immunologic response

  From baseline to month 15

• Persistence of DNA at the injection site

  At 1 and 6 months after last vaccination

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive pNGVL3-hICD vaccine admixed with GM-CSF intradermally once a month for 3 months in the absence of disease progression or unacceptable toxicity.

Biological: pNGVL3-hICD vaccine; Biological: sargramostim; Other: flow cytometry; Other: immunologic technique; Other: immunoenzyme technique; Genetic: protein expression analysis; Procedure: biopsy

Interventions

pNGVL3-hICD vaccine BIOLOGICAL

Plasmid-based DNA vaccine, given intradermally

Arm I

sargramostim BIOLOGICAL

Given intradermally

Also known as: GM-CSF, granulocyte macrophage colony-stimulating factor, Leukine, Prokine, rhu GM-CFS

Arm I

flow cytometry OTHER

Correlative studies

Arm I

immunologic technique OTHER

Correlative studies

Also known as: immunological laboratory methods, laboratory methods, immunological

Arm I

immunoenzyme technique OTHER

Undergo ELIspot (correlative studies)

Also known as: immunoenzyme techniques

Arm I

protein expression analysis GENETIC

Undergo ELISA (correlative studies)

Arm I

biopsy PROCEDURE

Undergo punch biopsy (correlative studies)

Also known as: biopsies

Arm I

Eligibility Criteria

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

You may qualify if:

• Breast cancer: stage III or stage IV breast cancer with metastasis in remission and defined as NED (no evidence of disease); stable or healing bone disease by radiologic evaluation which may include, but is not limited to, bone scan, MRI, or PET scan documented within 90 days of enrollment to study and NED status for extraskeletal metastasis
• Ovarian cancer: stage III or stage IV ovarian cancer in first complete remission with a normal AND stable CA-125; thus, two sequential normal CA-125 values will need to be documented; a minimum of 30 days between 2 sequential CA-125 values; the most recent will be within 2 weeks of enrollment into study
• HER2 overexpression by immunohistochemistry (IHC) of 2+ or 3+ in their primary tumor or metastasis, and if overexpression is 2+ by IHC or in the absence of IHC, then patients must have documentation of HER2 gene amplification by FISH
• Eligible subjects must have completed appropriate treatment for their primary disease and be off cytotoxic chemotherapy and corticosteroids for at least 1 month prior to enrollment; patients with stage III/IV breast cancer who have completed chemotherapy and are continued on trastuzumab monotherapy are eligible; hormonal and bisphosphanate therapies are allowed
• Subjects must have a Performance Status Score (Zubrod/ECOG Scale) = 0
• All subjects must no longer be able to bear children
• Hematocrit \>= 30
• Platelet count \>= 100,000
• WBC \>= 3,000/ul
• Creatinine =\< 2.0 or creatinine clearance \>= 60 ml/minute
• Serum bilirubin \< 1.5 mg/dl
• SGOT \< 2 x ULN
• Subjects must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have a significant active concurrent medical illness precluding protocol treatment or survival
• Normal ANA, anti-dsDNA and C3
• Patients on trastuzumab monotherapy must have adequate cardiac function as demonstrated by normal ejection fraction (EF) of MUGA scan or echocardiogram

You may not qualify if:

• Subjects cannot be simultaneously enrolled on other treatment studies
• Any contraindication to receiving GM-CSF based vaccine products
• Prior known history of cardiac disease, specifically restrictive cardiomyopathy, unstable angina within the last 6 months prior to enrollment, New York Heart Association functional class III-IV heart or symptomatic pericardial effusion
• Prior known history of pulmonary disease other than controlled asthma
• Active autoimmune disease
• Subjects cannot have active immunodeficiency disorder, e.g., HIV

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Disis MLN, Guthrie KA, Liu Y, Coveler AL, Higgins DM, Childs JS, Dang Y, Salazar LG. Safety and Outcomes of a Plasmid DNA Vaccine Encoding the ERBB2 Intracellular Domain in Patients With Advanced-Stage ERBB2-Positive Breast Cancer: A Phase 1 Nonrandomized Clinical Trial. JAMA Oncol. 2023 Jan 1;9(1):71-78. doi: 10.1001/jamaoncol.2022.5143.

  PMID: 36326756 DERIVED

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial; Breast Neoplasms

Interventions

sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; Colony-Stimulating Factors; Flow Cytometry; Immunologic Techniques; Immunoenzyme Techniques; Biopsy

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Immunoassay; Immunohistochemistry; Molecular Probe Techniques; Cytodiagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Mary L. Disis

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2007
• First Posted: February 19, 2007
• Study Start: October 1, 2001
• Primary Completion: March 1, 2010
• Study Completion: April 1, 2025
• Last Updated: April 6, 2025

Record last verified: 2025-04

Locations

US (1)