Vaccine Therapy in Treating HLA-A2 Positive Patients With Melanoma

NCT ID: NCT00003895

Last Updated: 2017-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-04-30
• Study Completion Date: 2013-09-30

Brief Summary

This randomized pilot phase II trial studies how well vaccine therapy works in treating human leukocyte antigen class 1 histocompatibility, A-2 (HLA-A2) positive patients with melanoma. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells.

Detailed Description

PRIMARY OBJECTIVES:

I. To define the toxicity of administration of gp100: 209-217 (210M) (gp100:209-217[210M] peptide vaccine) and the human papillomavirus (HPV) 16 E7(12-20) peptide (HPV16E7:12-20 peptide vaccine), with adjuvant Montanide ISA-51 (incomplete Freund's adjuvant), to patients who present with a primary melanoma > 1 mm thick.

II. To measure the T-cell response to the modified self-gp100: 209-217 (210M) peptide and the unmodified parental glycoprotein 100 (gp100) peptide.

III. To measure the T-cell response to the control human leukocyte antigen (HLA)-A2.1 restricted cytotoxic T-lymphocyte (CTL) epitope of papilloma virus HPV16E7:12-20.

IV. To determine whether analysis of antigen-specific T-cells using specific HLA-A2/peptide tetramers is an effective method for monitoring the immune response of patients undergoing peptide vaccination and to compare it to enzyme-linked immunosorbent spot (ELISPOT), limiting dilution analysis (LDA) and measurement of intracellular cytokine production (fastimmune).

V. To determine whether there is a difference between the induction of primary peptide-specific T-cell immune responses to the self gp100 peptide versus the foreign E7 peptide.

VI. To compare the immune response induced by vaccinating every 2 weeks for 6 months (a total of 13 vaccinations) vs. every 3 weeks for 6 months (a total of 9 vaccinations).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive gp100:209-217(210M) peptide vaccine and HPV16E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant subcutaneously (SC) every 2 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive gp100:209-217(210M) peptide vaccine and HPV16E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 3 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

In both arms, patients undergo sentinel lymph node biopsy approximately 10 days after the second vaccination. Patients with positive lymph nodes undergo complete lymph node dissection and resume vaccinations.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then yearly thereafter.

Conditions

Recurrent Melanoma; Stage IA Melanoma; Stage IB Melanoma; Stage IIA Melanoma; Stage IIB Melanoma; Stage IIC Melanoma; Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

gp100:209-217(210M) + HPV 16 E7:12-20 (every 2 weeks)

Patients receive gp100:209-217(210M) peptide vaccine and HPV 16 E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 2 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory biomarker analysis.

Group Type: EXPERIMENTAL

HPV 16 E7:12-20

Intervention Type: BIOLOGICAL

Given SC

gp100:209-217(210M)

Intervention Type: BIOLOGICAL

Given SC

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

gp100:209-217(210M) + HPV 16 E7:12-20 (every 3 weeks)

Patients receive gp100:209-217(210M) peptide vaccine and HPV 16 E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 3 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory biomarker analysis.

Group Type: EXPERIMENTAL

HPV 16 E7:12-20

Intervention Type: BIOLOGICAL

Given SC

gp100:209-217(210M)

Intervention Type: BIOLOGICAL

Given SC

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

HPV 16 E7:12-20

Given SC

Intervention Type: BIOLOGICAL

gp100:209-217(210M)

Given SC

Intervention Type: BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

G9 209-2M

Eligibility Criteria

Inclusion Criteria

• Patients must have histologically confirmed primary melanoma of Breslow thickness 1.0-4.0 mm; patients who have had only their initial biopsy are preferred; however, those who have already undergone a wide local excision are also eligible; patients may be enrolled up to three months after their wide local excision
• Patients whose melanoma is > 4.0 mm thick who have positive or negative regional lymph nodes are also eligible
• After accrual to the original 26 patient goal, all patients must be enrolled prior to sentinel lymph node dissection; patients with previous lymph node dissection will not be eligible
• Patients must be HLA typed and be shown to be HLA-A2.1+ by either serologic techniques, flow cytometry, or molecular techniques
• Patients must be ambulatory with good performance status (Karnofsky performance status [PS] 80-100)
• White blood cell (WBC) >= 3500/mm^3
• Platelets (Plt) >= 100,000/mm^3
• Hemoglobin >= 9 gm/100 ml
• Serum creatinine =< 2 mg/dl
• Total bilirubin =< 2.0 mg/dl
• Patients must have recovered from any effects of major surgery and be free of significant systemic infection
• Patients must be negative for human immunodeficiency virus (HIV) antibody by enzyme-linked immunosorbent assay (ELISA) (or negative by Western blot if ELISA is positive) if they are considered to be at high risk; others do not require serologic testing if there are no symptoms or risk factors for HIV disease
• Women of childbearing potential must have a negative pregnancy test and should avoid becoming pregnant while on treatment
• Patients must give written informed consent prior to initiation of therapy; patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy

Exclusion Criteria

• Patients must not have clinically detectable distant metastases
• Patients who require or are likely to require systemic corticosteroids for intercurrent illness
• Patients with any significant medical disease other than the malignancy (e.g. chronic obstructive pulmonary disorder [COPD], patients with ascites or pleural effusions) which in the opinion of the investigator would significantly increase the risk of immunotherapy
• Patient should be free of any other cancers or deemed at low risk for their recurrence

• Minimum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Walter J. Urba, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Providence Cancer Center, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center

Locations

Providence Portland Medical Center

Portland, Oregon, United States

Countries

United States

Other Identifiers

NCI-2013-02096

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000067065

Identifier Type: -

Identifier Source: secondary_id

NCI-T98-0081

Identifier Type: -

Identifier Source: secondary_id

PPMC-IRB-99-9

Identifier Type: OTHER

Identifier Source: secondary_id

99-9

Identifier Type: OTHER

Identifier Source: secondary_id

T98-0081

Identifier Type: OTHER

Identifier Source: secondary_id

R21CA082614

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2013-02096

Identifier Type: -

Identifier Source: org_study_id

NCT02009657

Identifier Type: -

Identifier Source: nct_alias