Vaccine Therapy in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

NCT ID: NCT00471471

Last Updated: 2017-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2011-12-31

Brief Summary

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving vaccine therapy together with GM-CSF, CpG 7909, and incomplete Freund's adjuvant may make a stronger immune response and kill more tumor cells.

PURPOSE: This clinical trial is studying the side effects and how well vaccine therapy works in treating patients with recurrent stage III or stage IV melanoma that cannot be removed by surgery.

Detailed Description

OBJECTIVES:

• Determine the safety of a peptide vaccine comprising MART-1:27-35 peptide, gp100:209-217 (210M) peptide, and tyrosinase peptide with sargramostim (GM-CSF) and CpG 7909 emulsified in incomplete Freund's adjuvant in patients with unresectable recurrent stage III or IV melanoma.
• Determine the efficacy of immunoadjuvants CpG 7909 and GM-CSF, in terms of a strong antigen-specific CD8+ T-cell response, in these patients.
• Determine the anti-pigmentary response to this regimen in these patients.
• Determine the anti-tumor response, in terms of objective tumor regression, progression-free survival, and overall survival, in patients treated with this regimen.

OUTLINE: This is a pilot study.

Patients receive peptide vaccine comprising MART-1:27-35 peptide, gp100:209-217 (210M) peptide, and tyrosinase peptide with sargramostim (GM-CSF) and CpG 7909 emulsified in incomplete Freund's adjuvant subcutaneously on days 1 and 15. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline, day 50-53, and day 91-94. Samples are examined by ELISPOT assay to measure lymphocyte immune response and by flow cytometry for biomarker quantification and T-cell response.

After completion of study treatment, patients are followed up periodically for at least 2 years.

Conditions

Intraocular Melanoma; Malignant Conjunctival Neoplasm; Melanoma (Skin)

Study Design

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

Study Groups

Peptide Vaccine + GM-CSF + Pfizer 3512676 in-ISA Oil

The water-in-oil emulsion will consist of peptide (100 mcg/0.1 mL), GM-CSF (80 mcg/0.16 mL using lyophilized 500 mcg/vial reconstituted with 1 mL of sterile water), Pfizer PF3512676 (0.6 mg/0.04 mL using 15mg/mL vial) and 0.20 mLl of sterile saline.

Vaccination will be given subcutaneously rotating truncal sites in the vicinity of the four nodal drainage groups of the four extremities, on days 1 and 15 of each cycle (1 cycle = 28 days) for a maximum of 13 cycles (1 year).

Group Type: EXPERIMENTAL

Peptide vaccine

Intervention Type: BIOLOGICAL

Multi-epitope peptide vaccine containing MART-1 (26-35, 27L), gp100 (209-217, 210M) and tyrosinase (368-376, 370D) peptides

GM-CSF

Intervention Type: BIOLOGICAL

80 mcg/0.16 mL using lyophilized 500 mcg/vial reconstituted with 1 mL of sterile water given subcutaneously rotating truncal sites in the vicinity of the four nodal drainage groups of the four extremities, on days 1 and 15 of each cycle (1 cycle = 28 days) for a maximum of 13 cycles (1 year).

PF3512676

Intervention Type: BIOLOGICAL

0.6 mg/0.04 mL given subcutaneously rotating truncal sites in the vicinity of the four nodal drainage groups of the four extremities, on days 1 and 15 of each cycle (1 cycle = 28 days) for a maximum of 13 cycles (1 year).

Interventions

Peptide vaccine

Multi-epitope peptide vaccine containing MART-1 (26-35, 27L), gp100 (209-217, 210M) and tyrosinase (368-376, 370D) peptides

Intervention Type: BIOLOGICAL

GM-CSF

80 mcg/0.16 mL using lyophilized 500 mcg/vial reconstituted with 1 mL of sterile water given subcutaneously rotating truncal sites in the vicinity of the four nodal drainage groups of the four extremities, on days 1 and 15 of each cycle (1 cycle = 28 days) for a maximum of 13 cycles (1 year).

Intervention Type: BIOLOGICAL

PF3512676

0.6 mg/0.04 mL given subcutaneously rotating truncal sites in the vicinity of the four nodal drainage groups of the four extremities, on days 1 and 15 of each cycle (1 cycle = 28 days) for a maximum of 13 cycles (1 year).

Intervention Type: BIOLOGICAL

Other Intervention Names

Sargramostim; CpG 7909; agatolimod

Eligibility Criteria

Inclusion Criteria

• More than 2 weeks since prior and no concurrent treatment with systemic steroids, including oral steroids, continuous use of topical steroid creams or ointments, or any inhaled steroids
• No concurrent anticoagulants, except to keep an indwelling line patent
• No other concurrent anticancer therapy, including chemotherapy, immunotherapy, radiotherapy, experimental programs, and/or surgery

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Ahmad Tarhini

OTHER

Sponsor Role: lead

Responsible Party

Ahmad Tarhini

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ahmad A. Tarhini, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

UPMC Cancer Centers

Pittsburgh, Pennsylvania, United States

Countries

United States

References

Tarhini AA, Leng S, Moschos SJ, Yin Y, Sander C, Lin Y, Gooding WE, Kirkwood JM. Safety and immunogenicity of vaccination with MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) in adjuvant with PF-3512676 and GM-CSF in metastatic melanoma. J Immunother. 2012 May;35(4):359-66. doi: 10.1097/CJI.0b013e31825481fe.

Reference Type: RESULT

PMID: 22495394 (View on PubMed)

Other Identifiers

NCI-2009-00159

Identifier Type: REGISTRY

Identifier Source: secondary_id

PCI-IRB-0607048

Identifier Type: -

Identifier Source: secondary_id

CDR0000544402

Identifier Type: REGISTRY

Identifier Source: secondary_id

04-173

Identifier Type: -

Identifier Source: org_study_id