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

NCT ID: NCT00436254

Last Updated: 2025-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-10-31
• Study Completion Date: 2025-04-01

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.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the safety of intradermal administration of 3 doses of a plasmid-based DNA vaccine encoding the ICD of HER2 administered with a fixed dose of GM-CSF. II. To determine whether a plasmid DNA vaccine encoding the ICD of HER2 can elicit HER2 specific immune responses. SECONDARY OBJECTIVES: I. To determine if the dose of the plasmid-based DNA vaccine effects immunologic responses. II. To determine the persistence of DNA at the site of vaccination. OUTLINE: This is a dose-escalation study of a plasmid-based DNA (pNGVL3-hICD) vaccine. 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. After completion of study treatment, patients are followed up periodically for up to 15 years with primary physicians.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

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.

Group Type: EXPERIMENTAL

pNGVL3-hICD vaccine

Intervention Type: BIOLOGICAL

Plasmid-based DNA vaccine, given intradermally

sargramostim

Intervention Type: BIOLOGICAL

Given intradermally

flow cytometry

Intervention Type: OTHER

Correlative studies

immunologic technique

Intervention Type: OTHER

Correlative studies

immunoenzyme technique

Intervention Type: OTHER

Undergo ELIspot (correlative studies)

protein expression analysis

Intervention Type: GENETIC

Undergo ELISA (correlative studies)

biopsy

Intervention Type: PROCEDURE

Undergo punch biopsy (correlative studies)

Interventions

pNGVL3-hICD vaccine

Plasmid-based DNA vaccine, given intradermally

Intervention Type: BIOLOGICAL

sargramostim

Given intradermally

Intervention Type: BIOLOGICAL

flow cytometry

Correlative studies

Intervention Type: OTHER

immunologic technique

Correlative studies

Intervention Type: OTHER

immunoenzyme technique

Undergo ELIspot (correlative studies)

Intervention Type: OTHER

protein expression analysis

Undergo ELISA (correlative studies)

Intervention Type: GENETIC

biopsy

Undergo punch biopsy (correlative studies)

Intervention Type: PROCEDURE

Other Intervention Names

GM-CSF; granulocyte macrophage colony-stimulating factor; Leukine; Prokine; rhu GM-CFS; immunological laboratory methods; laboratory methods, immunological; immunoenzyme techniques; biopsies

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary L. Disis

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36326756 (View on PubMed)

Other Identifiers

NCI-2010-00869

Identifier Type: -

Identifier Source: secondary_id

RG1704001

Identifier Type: OTHER

Identifier Source: secondary_id

6532

Identifier Type: -

Identifier Source: org_study_id

NCT00194662

Identifier Type: -

Identifier Source: nct_alias