Vaccine Therapy in Treating Patients With Advanced Melanoma

NCT00705640 | Completed Phase 1 DMC

• 6 other identifiers: 13498R01CA057653P30CA044579UVACC-MEL-48UVACC-IRB-13498UVACC-PRC-450-07
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Vaccine therapy may help the body build an effective immune response to kill tumor cells. PURPOSE: This randomized clinical trial is studying how well vaccine therapy works in treating patients with advanced melanoma.

Conditions

Intraocular Melanoma; Malignant Conjunctival Neoplasm; Melanoma (Skin)

Keywords

stage II melanoma; stage III melanoma; stage IV melanoma; ciliary body and choroid melanoma, medium/large size; ciliary body and choroid melanoma, small size; conjunctival melanoma; extraocular extension melanoma; iris melanoma; metastatic intraocular melanoma; recurrent intraocular melanoma

Outcome Measures

Primary Outcomes (1)

• Features of lymphoid neogenesis at the replicate immunization site

  Up to Day 85

Study Arms (10)

Arm 1A

EXPERIMENTAL

Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive no replicate vaccine. Patients undergo surgical biopsy at replicate vaccine site on day 1.

Biological: incomplete Freund's adjuvant; Biological: multi-epitope melanoma peptide vaccine; Biological: tetanus toxoid helper peptide; Procedure: biopsy

Arm 1B

EXPERIMENTAL

Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine comprising incomplete Freund's adjuvant only SC and ID on day 1 and undergo surgical biopsy at replicate vaccine site on day 8 (1 week after replicate vaccine 1).

Biological: incomplete Freund's adjuvant; Biological: multi-epitope melanoma peptide vaccine; Biological: tetanus toxoid helper peptide; Procedure: biopsy

Arm 1C

EXPERIMENTAL

Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine comprising incomplete Freund's adjuvant only SC and ID on days 1, 8, and 15 and undergo surgical biopsy at replicate vaccine site on day 22 (1 week after replicate vaccine 3).

Biological: incomplete Freund's adjuvant; Biological: multi-epitope melanoma peptide vaccine; Biological: tetanus toxoid helper peptide; Procedure: biopsy

Arm 1D

EXPERIMENTAL

Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine comprising incomplete Freund's adjuvant only SC and ID on days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate vaccine site on day 50 (1 week after replicate vaccine 6). Patients are evaluated 1-3 weeks after biopsy.

Biological: incomplete Freund's adjuvant; Biological: multi-epitope melanoma peptide vaccine; Biological: tetanus toxoid helper peptide; Procedure: biopsy

Arm 1E

EXPERIMENTAL

Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine comprising incomplete Freund's adjuvant only SC and ID on days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate vaccine site on day 85 (6 week after replicate vaccine 6). Patients are evaluated 1-3 weeks after biopsy.

Biological: incomplete Freund's adjuvant; Biological: multi-epitope melanoma peptide vaccine; Biological: tetanus toxoid helper peptide; Procedure: biopsy

Arm 2A

EXPERIMENTAL

Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive no replicate vaccine. Patients undergo surgical biopsy at replicate vaccine site on day 1.

Biological: incomplete Freund's adjuvant; Biological: multi-epitope melanoma peptide vaccine; Biological: tetanus toxoid helper peptide; Procedure: biopsy

Arm 2B

EXPERIMENTAL

Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine (the same as primary vaccine) SC and ID on day 1 and undergo surgical biopsy at replicate vaccine site on day 8 (1 week after replicate vaccine 1).

Biological: incomplete Freund's adjuvant; Biological: multi-epitope melanoma peptide vaccine; Biological: tetanus toxoid helper peptide; Procedure: biopsy

Arm 2C

EXPERIMENTAL

Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine (the same as primary vaccine) SC and ID on days 1, 8, and 15 and undergo surgical biopsy at replicate vaccine site on day 22 (1 week after replicate vaccine 3).

Biological: incomplete Freund's adjuvant; Biological: multi-epitope melanoma peptide vaccine; Biological: tetanus toxoid helper peptide; Procedure: biopsy

Arm 2D

EXPERIMENTAL

Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine (the same as primary vaccine) SC and ID on days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate vaccine site on day 50 (1 week after replicate vaccine 6). Patients are evaluated 1-3 weeks after biopsy.

Biological: incomplete Freund's adjuvant; Biological: multi-epitope melanoma peptide vaccine; Biological: tetanus toxoid helper peptide; Procedure: biopsy

Arm 2E

EXPERIMENTAL

Patients receive primary vaccine, half of the volume subcutaneously (SC) and the other half intradermally (ID), 6 times over 7 weeks on days 1, 8, 15, 29, 36, and 43. Patients receive replicate vaccine (the same as primary vaccine) SC and ID on days 1, 8, 15, 29, 36, and 43 and undergo surgical biopsy at replicate vaccine site on day 85 (1 week after replicate vaccine 6). Patients are evaluated 1-3 weeks after biopsy.

Biological: incomplete Freund's adjuvant; Biological: multi-epitope melanoma peptide vaccine; Biological: tetanus toxoid helper peptide; Procedure: biopsy

Interventions

incomplete Freund's adjuvant BIOLOGICAL

Given subcutaneously and intradermally

Arm 1A; Arm 1B; Arm 1C; Arm 1D; Arm 1E; Arm 2A; Arm 2B; Arm 2C; Arm 2D; Arm 2E

multi-epitope melanoma peptide vaccine BIOLOGICAL

Given subcutaneously and intradermally

Arm 1A; Arm 1B; Arm 1C; Arm 1D; Arm 1E; Arm 2A; Arm 2B; Arm 2C; Arm 2D; Arm 2E

tetanus toxoid helper peptide BIOLOGICAL

Given subcutaneously and intradermally

Arm 1A; Arm 1B; Arm 1C; Arm 1D; Arm 1E; Arm 2A; Arm 2B; Arm 2C; Arm 2D; Arm 2E

biopsy PROCEDURE

Patients undergo surgical biopsy at replicate vaccine site

Arm 1A; Arm 1B; Arm 1C; Arm 1D; Arm 1E; Arm 2A; Arm 2B; Arm 2C; Arm 2D; Arm 2E

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed melanoma that meets one of the following criteria: * Stage IIB-IV melanoma rendered clinically free of disease by surgery, other therapy, or spontaneous remission within the past 6 months * Stage III or IV melanoma with disease * Persistent or metastatic disease allowed if RECIST criteria for measurable disease is not met * Multiple primary melanomas allowed * Prior or concurrent metastasis from a cutaneous, mucosal, ocular, or unknown primary site allowed * No clinically detectable melanoma deemed likely by the investigator to require intervention during the first 12 weeks of the study that would require premature discontinuation (e.g., untreated bone metastases at risk for fracture or rapidly progressive low-volume disease) * Brain metastases allowed if all of the following criteria are met: * The total number of brain metastases ever is ≤ 3 * The brain metastases have been completely removed by surgery or have been treated completely by stereotactic radiotherapy * There has been no evident growth of any brain metastasis since treatment * No treated brain metastasis \> 2 cm in diameter * At least two intact axillary and/or inguinal lymph node basins * Prior lymph node biopsy allowed if lymphoscintigraphy demonstrates intact drainage to a node in that basin * If a sentinal lymph node is not located by lymphoscintigraphy, patient is not eligible for study * HLA-A1, -A2, -A3, or -A11 positive * Either eligible for, but refused interferon therapy OR not a candidate for interferon therapy for the following reasons: * Active ischemic heart disease or cerebrovascular disease * Anginal syndrome requiring ongoing medications or history of myocardial infarction or arrhythmia disorder * History of treatment for depression, active depression, or other psychiatric disorder * Autoimmune disorders * Hypersensitivity to interferon-alfa or any component associated with interferon therapy * Debilitating medical conditions such as severe pulmonary disease or severe diabetes mellitus * Thyroid abnormalities, where thyroid function cannot be maintained in the normal range without medication * Resected stage IV melanoma * Discontinued interferon therapy due to the occurrence of a major toxicity that has been documented by the treating physician * Experienced tumor progression while on interferon or after completing interferon therapy * Missed the standard-of-care enrollment window for interferon therapy initiation PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * ANC \> 1,000/mm\^3 * Platelets \> 100,000/mm\^3 * Hemoglobin \> 9 g/dL * AST and ALT ≤ 2.5 times upper limit of normal (ULN) * Bilirubin ≤ 2.5 times ULN * Alkaline phosphatase ≤ 2.5 times ULN * Creatinine ≤ 1.5 times ULN * Hepatitis C and HIV negative (antibody screening) * Hemoglobin\_A1C level \< 7% * Body weight ≥ 110 pounds * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during study treatment * No New York Heart Association class III-IV heart disease * No known or suspected allergies to any component of the vaccine * No medical contraindication or potential problem in complying with the requirements of the protocol PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Prior peptide vaccines (including MELITAC 12.1 and similar vaccines) or non-peptide vaccines allowed * At least 1 week since prior stereotactic radiotherapy, such as gamma knife * No influenza vaccine ≥ 2 weeks before, during, and ≥ 2 weeks after completion of study therapy * More than 4 weeks since prior and no concurrent use of any of the following: * Systemic cytotoxic chemotherapy (6 weeks for nitrosoureas) * Radiotherapy * Other experimental therapy * Agents with putative immunomodulating activity (with the exception of non-steroidal anti-inflammatory agents and topical steroids) * Allergy desensitization injections * Systemic corticosteroids, administered parenterally or orally * Inhaled steroids (e.g., fluticasone propionate \[Advair® or Flovent®\] or triamcinolone acetonide \[Azmacort®\]) * Topical corticosteroids and steroids with very low solubility administered nasally for local effects only allowed (e.g., mometasone furoate \[Nasonex®\]) * Growth factors (e.g., sargramostim \[GM-CSF\], filgrastim \[G-CSF\], or epoetin alfa) * Interferon therapy * Aldesleukin or other interleukins * Street drugs * At least 1 month since prior and no other concurrent investigational drugs or therapy * At least 12 weeks since prior melanoma vaccine for patients who have recurred or progressed either after or during treatment with vaccine

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Craig L Slingluff, Jr: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Related Publications (3)

• Pollack KE, Meneveau MO, Melssen MM, Lynch KT, Koeppel AF, Young SJ, Turner S, Kumar P, Sol-Church K, Mauldin IS, Slingluff CL Jr. Incomplete Freund's adjuvant reduces arginase and enhances Th1 dominance, TLR signaling and CD40 ligand expression in the vaccine site microenvironment. J Immunother Cancer. 2020 Apr;8(1):e000544. doi: 10.1136/jitc-2020-000544.

  PMID: 32350119 DERIVED

• Judge JM, Chianese-Bullock KA, Schroen AT, Slingluff CL Jr. Usefulness of prestudy assessment of patient willingness to undergo tissue biopsy for correlative studies in a melanoma vaccine trial. Clin Trials. 2013 Feb;10(1):143-50. doi: 10.1177/1740774512464438. Epub 2012 Nov 29.

  PMID: 23197414 DERIVED

• Schaefer JT, Patterson JW, Deacon DH, Smolkin ME, Petroni GR, Jackson EM, Slingluff CL Jr. Dynamic changes in cellular infiltrates with repeated cutaneous vaccination: a histologic and immunophenotypic analysis. J Transl Med. 2010 Aug 20;8:79. doi: 10.1186/1479-5876-8-79.

  PMID: 20727190 DERIVED

MeSH Terms

Conditions

Uveal Melanoma; Melanoma

Interventions

incomplete Freund's adjuvant; Biopsy

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Craig L. Slingluff, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgery; Director, Human Immune Therapy Center

Study Record Dates

• First Submitted: June 25, 2008
• First Posted: June 26, 2008
• Study Start: May 1, 2008
• Primary Completion: June 1, 2009
• Last Updated: December 16, 2016

Record last verified: 2016-12

Locations

US (1)