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

Primary Purpose

Intraocular Melanoma, Malignant Conjunctival Neoplasm, Melanoma (Skin)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Peptide vaccine
GM-CSF
PF3512676
Sponsored by
Ahmad Tarhini
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intraocular Melanoma focused on measuring recurrent melanoma, stage IV melanoma, ciliary body and choroid melanoma, medium/large size, extraocular extension melanoma, iris melanoma, recurrent intraocular melanoma, metastatic intraocular melanoma, conjunctival melanoma, stage IIIA melanoma, stage IIIB melanoma, stage IIIC melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Histologically confirmed melanoma meeting the following criteria:

    • Unresectable recurrent disease
    • Stage III or IV disease
    • Cutaneous, ocular, or mucosal melanoma
  • Measurable disease as defined by the RECIST criteria
  • HLA-A2 positive
  • Prior brain metastases allowed provided adequate surgical or radiologic treatment for brain disease

PATIENT CHARACTERISTICS:

  • ECOG performance status 0 or 1
  • WBC ≥ 3,000/mm³
  • Lymphocytes ≥ 1,000/mm³
  • Platelet count ≥ 100,000/mm³
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • AST and ALT ≤ 2.5 times ULN
  • Lactic dehydrogenase ≤ 2.0 times ULN
  • aPTT < 40 seconds
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception for ≥ 1 week before, during, and for ≥ 2 weeks after completion of study therapy
  • No conditions of immunosuppression
  • Negative titers for antinuclear antibody (≤ 1/80) and antidouble stranded DNA (≤ 1/10)

  • No serious illnesses including, but not limited to, any of the following:

    • Bleeding disorders
    • Autoimmune diseases
    • Severe obstructive or restrictive pulmonary diseases
    • Active systemic infections
    • Inflammatory bowel disorders

  • No serious cardiovascular disease including, but not limited to, any of the following:

    • Uncontrolled congestive heart failure
    • Hypertension
    • Cardiac ischemia
    • Myocardial infarction,
    • Severe cardiac arrhythmia
  • HIV1 and 2 negative
  • HTLV-1 negative
  • Hepatitis B and C negative
  • No significant psychiatric disease, medical intervention, or other condition that, in the opinion of the principal investigator, would limit study compliance
  • No active infection within the past week, including unexplained fever (temperature > 38.1°C)

PRIOR CONCURRENT THERAPY:

  • Fully recovered from prior major surgery
  • More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas), hormonal therapy, radiotherapy, or biological therapy
  • More than 1 week since prior antibiotics
  • More than 28 days since prior investigational agent

  • No prior vaccination with MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) peptides alone or in combination

    • Patients with history of vaccination with peptides other than MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) peptides allowed

  • More than 4 weeks since prior and no concurrent systemic immunosuppressive therapy, including steroids

    • Patients on maintenance steroids given at physiologic doses because of adrenal insufficiency are eligible
  • 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

Sites / Locations

  • UPMC Cancer Centers

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm Description

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).

Outcomes

Primary Outcome Measures

Safety
Number of grade 2 or greater allergic reactions (including generalized urticaria) or any grade 3 or greater adverse event

Secondary Outcome Measures

Immunologic response
Change in the circulating effector T-cells.
Objective tumor regression
Change in tumor size will be performed at the end of cycle 2.
Depigmentation evaluation
Change in cutaneous depigmentation using careful inspection of the skin of the torso by a Wood's lamp.

Full Information

First Posted
May 8, 2007
Last Updated
June 21, 2017
Sponsor
Ahmad Tarhini
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00471471
Brief Title
Vaccine Therapy in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
Official Title
Safety and Immunogenicity of Vaccination With Multi-Epitope Peptide Vaccine Containing MART-1, gp100, and Tyrosinase Peptides Given With the Combination of GMCSF and CpG Oligonucleotide (CpG 7909) in ISA-Oil Adjuvant for Patients With Recurrent Inoperable Stage III or Stage IV Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ahmad Tarhini
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intraocular Melanoma, Malignant Conjunctival Neoplasm, Melanoma (Skin)
Keywords
recurrent melanoma, stage IV melanoma, ciliary body and choroid melanoma, medium/large size, extraocular extension melanoma, iris melanoma, recurrent intraocular melanoma, metastatic intraocular melanoma, conjunctival melanoma, stage IIIA melanoma, stage IIIB melanoma, stage IIIC melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Peptide Vaccine + GM-CSF + Pfizer 3512676 in-ISA Oil
Arm Type
Experimental
Arm Description
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).
Intervention Type
Biological
Intervention Name(s)
Peptide vaccine
Intervention Description
Multi-epitope peptide vaccine containing MART-1 (26-35, 27L), gp100 (209-217, 210M) and tyrosinase (368-376, 370D) peptides
Intervention Type
Biological
Intervention Name(s)
GM-CSF
Other Intervention Name(s)
Sargramostim
Intervention Description
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
Intervention Name(s)
PF3512676
Other Intervention Name(s)
CpG 7909, agatolimod
Intervention Description
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).
Primary Outcome Measure Information:
Title
Safety
Description
Number of grade 2 or greater allergic reactions (including generalized urticaria) or any grade 3 or greater adverse event
Time Frame
up to 1 year
Secondary Outcome Measure Information:
Title
Immunologic response
Description
Change in the circulating effector T-cells.
Time Frame
up to 94 days
Title
Objective tumor regression
Description
Change in tumor size will be performed at the end of cycle 2.
Time Frame
2 months
Title
Depigmentation evaluation
Description
Change in cutaneous depigmentation using careful inspection of the skin of the torso by a Wood's lamp.
Time Frame
up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed melanoma meeting the following criteria: Unresectable recurrent disease Stage III or IV disease Cutaneous, ocular, or mucosal melanoma Measurable disease as defined by the RECIST criteria HLA-A2 positive Prior brain metastases allowed provided adequate surgical or radiologic treatment for brain disease PATIENT CHARACTERISTICS: ECOG performance status 0 or 1 WBC ≥ 3,000/mm³ Lymphocytes ≥ 1,000/mm³ Platelet count ≥ 100,000/mm³ Creatinine ≤ 1.5 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN AST and ALT ≤ 2.5 times ULN Lactic dehydrogenase ≤ 2.0 times ULN aPTT < 40 seconds Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception for ≥ 1 week before, during, and for ≥ 2 weeks after completion of study therapy No conditions of immunosuppression Negative titers for antinuclear antibody (≤ 1/80) and antidouble stranded DNA (≤ 1/10) No serious illnesses including, but not limited to, any of the following: Bleeding disorders Autoimmune diseases Severe obstructive or restrictive pulmonary diseases Active systemic infections Inflammatory bowel disorders No serious cardiovascular disease including, but not limited to, any of the following: Uncontrolled congestive heart failure Hypertension Cardiac ischemia Myocardial infarction, Severe cardiac arrhythmia HIV1 and 2 negative HTLV-1 negative Hepatitis B and C negative No significant psychiatric disease, medical intervention, or other condition that, in the opinion of the principal investigator, would limit study compliance No active infection within the past week, including unexplained fever (temperature > 38.1°C) PRIOR CONCURRENT THERAPY: Fully recovered from prior major surgery More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas), hormonal therapy, radiotherapy, or biological therapy More than 1 week since prior antibiotics More than 28 days since prior investigational agent No prior vaccination with MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) peptides alone or in combination Patients with history of vaccination with peptides other than MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) peptides allowed More than 4 weeks since prior and no concurrent systemic immunosuppressive therapy, including steroids Patients on maintenance steroids given at physiologic doses because of adrenal insufficiency are eligible 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ahmad A. Tarhini, MD, MS
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
UPMC Cancer Centers
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22495394
Citation
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. Erratum In: J Immunother. 2012 Oct;35(8):650.
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Vaccine Therapy in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

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