Long Peptide Vaccine (LPV7) Plus TLR Agonists in Treating Participants with Resected Stage IIB-IV Melanoma

Status: Active

Description

This phase I / II trial studies the side effects and best combination of long peptide vaccine (LPV7) when combined with toll-like receptor agonists (TLR) such as tetanus peptide melanoma vaccine, incomplete Freund's adjuvant, poly ICLC and resiquimod gel in treating participants with stage IIb-IV melanoma that has been removed by surgery. Vaccines made from peptides or antigens may help the body build an effective immune response to kill tumor cells.

Eligibility Criteria

Inclusion Criteria

  • Histologically or cytologically proven Stage IIb-IV melanoma (at diagnosis or at the time of recurrence) rendered clinically free of disease by surgery, other therapy, or spontaneous remission within 6 months prior to registration; patients with treated brain metastases may be eligible if they meet the criteria. Small radiologic or clinical findings of an indeterminate nature will not be a basis for exclusion, and brain metastases will not be a basis for exclusion. * Staging of cutaneous melanoma will be based on the 7th edition American Joint Committee on Cancer (AJCC) staging system. Staging of mucosal melanomas will be based on the following system modified from the cutaneous melanoma staging system: 2.01- 4 mm primary with ulceration or > 4 mm primary = stage IIb, lymph node metastases = stage III, distant metastases = stage IV.
  • Patients may have had multiple primary melanomas.
  • Patients may have had or may have a metastasis from a cutaneous primary site, mucosal primary site, or unknown primary site.
  • Patients with brain metastases may be eligible if all of the following are true: * The total number of brain metastases ever is less than or equal to 3. * The brain metastases have been completely removed by surgery or have been treated completely by stereotactic radiotherapy. Stereotactic radiotherapy, such as gamma knife, can be used up to 1 week prior to study entry. In the absence of concerning clinical findings, repeat scans are not required after stereotactic radiotherapy if the patient enrolls within 8 weeks of completing the stereotactic therapy. * There has been no evident growth of any brain metastasis since treatment. * No treated brain metastasis is greater than 2 cm in diameter at the time of protocol entry.
  • Patients must have at least one axillary and/or inguinal lymph node basin that is intact (no prior excisional biopsy of a node or complete lymph node dissection).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Ability and willingness to give informed consent.
  • Human leukocyte antigen (HLA)-A1, A2, A3, B35, or B51.
  • Absolute neutrophil count (ANC) > 1000/mm^3.
  • Platelets > 100,000/mm^3.
  • Hemoglobin (Hgb) > 9 g/dL.
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) up to 2.5 x upper limits of normal (ULN). * Patients known to have Gilbert’s disease may be eligible with AST and ALT up to 5 x ULN.
  • Bilirubin up to 2.5 x ULN.
  • Alkaline phosphatase up to 2.5 x ULN.
  • Creatinine up to 1.5 x ULN.
  • Glycated hemoglobin (Hgb-A1C) level of =< 7.5%.

Exclusion Criteria

  • Patients who have had brain metastases unless they meet the criteria.
  • Patients with melanoma arising from uveal/ocular primary sites.
  • Patients who are currently receiving systemic cytotoxic chemotherapy, radiation, targeted molecular therapy (e.g. vemurafenib, other inhibitor of mutant BRAF, MEK, or cKit), or other experimental therapy, or who have received this therapy within the preceding 4 weeks (except as specified). Gamma knife or stereotactic radiosurgery may be administered within the prior 4 weeks, but must not be administered less than one week prior to study registration. Patients who are currently receiving nitrosoureas or who have received this therapy within the preceding 6 weeks are excluded.
  • Patients who are receiving or have been treated with antibody to CTLA4 (e.g. ipilimumab), PD-1, PD-L1, CD137, or CD27 within the prior 12 months. Any patient who has had one or more of these therapies greater than 12 months prior and is clinically free of disease and totally recovered from toxicities related to those therapies can be eligible.
  • Patients with known or suspected allergies to any component of the vaccine.
  • Human immunodeficiency virus (HIV) positivity or evidence of active hepatitis C virus.
  • Patients receiving the following medications at study entry or within the preceding 4 weeks are excluded: * 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. Advair, Flovent, Azmacort) are not permitted. Topical corticosteroids are acceptable, including steroids with very low solubility administered nasally for local effects only (e.g. Nasonex). * Any growth factors (e.g. granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF), erythropoietin). * Interferon therapy. * Interleukin-2 or other interleukins. * For immune modulating agents, it may be necessary for more than 4 weeks to have elapsed since completion of that therapy.
  • Prior melanoma vaccinations may be an exclusion criterion in the following circumstances: * Patients who have received, within the prior 5 years, melanoma vaccines or other vaccines containing an incomplete Freund’s adjuvant (IFA; such as montanide ISA-51). * Patients who have received any melanoma vaccine within the past 12 months. * Patients who have been vaccinated in the past with any of the melanoma peptides in the LPV7 vaccine included in this study.
  • Other investigational drugs or investigational therapy if the patient is currently taking those drugs/therapy, or if they have received the drugs/therapy within 1 month.
  • Pregnancy or the possibility of becoming pregnant during vaccine administration. Female patients of child-bearing potential must have a negative pregnancy test (urinary or serum beta-human chorionic gonadotropin [HCG]) prior to administration of the first vaccine dose. Males and females must agree, in the consent form, to use effective birth control methods during the course of vaccination. Women must also not be breast feeding. This is consistent with existing standards of practice for vaccine and chemotherapy protocols.
  • Participants must not have had prior autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement. Participants with an active autoimmune disorder requiring these therapies are also excluded. The following will not be exclusionary: * The presence of laboratory evidence of autoimmune disease (e.g. positive antinuclear antibodies [ANA] titer) without symptoms. * Clinical evidence of vitiligo. * Hypothyroidism of any etiology on stable thyroid hormone replacement therapy. * Other forms of depigmenting illness. * Mild arthritis requiring nonsteroidal antiinflammatory drug (NSAID) medications.
  • Patients in whom there is a medical contraindication or potential problem in complying with the requirements of the protocol, in the opinion of the investigator.
  • Patients classified according to the New York Heart Association classification as having class III or IV heart disease.
  • Patients with a body weight < 110 pounds (lbs) (50 kilograms [kg]) because of the amount and frequency with which blood will be drawn, and because of the skin biopsies required.

Locations & Contacts

Texas

Houston
M D Anderson Cancer Center
Status: Active
Contact: Sapna Pradyuman Patel
Phone: 713-792-2921
Email: sppatel@mdanderson.org

Virginia

Charlottesville
University of Virginia Cancer Center
Status: Active
Contact: Craig Lee Slingluff
Phone: 434-924-1730
Email: cls8h@virginia.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To assess safety of vaccination with a mixture of long peptides for patients with high-risk melanoma, in each of 7 adjuvant preparations, including TLR agonists and/or incomplete Freund’s adjuvant (IFA). (Part I, completed)

II. To estimate the immunogenicity of 7 long peptides in each of 7 adjuvant preparations. (Part I, completed)

SECONDARY OBJECTIVES:

I. To evaluate the molecular and cellular changes at the vaccine site and systemically. (Part I, completed)

II. To assess safety of vaccination of the optimal combination identified in Part 1 when administered in the same skin site for all 6 vaccines (same site vaccination). (Part II)

III. To estimate the immunogenicity of the optimal combination identified in Part 1 when administered in the same skin site for all 6 vaccines (same site vaccination). (Part II)

OUTLINE: Participants are randomized to 1 of 8 arms.

ARM A (IFA) (Part I): Participants receive long peptide vaccine (LPV7), tetanus peptide, and IFA half intradermally (ID) and half subcutaneously (SC) on days 1, 8, 15, 36, 57, and 78 in the absence of disease progression or unacceptable toxicity.

ARM B (polyICLC) (Part I): Participants receive LPV7, tetanus peptide, and poly ICLC half ID and half SC on days 1, 8, 15, 36, 57, and 78 in the absence of disease progression or unacceptable toxicity.

ARM C (resiquimod) (Part I): Participants receive LPV7 and tetanus peptide half ID and half SC, and resiquimod topically to vaccine site immediately after vaccine administration on days 1, 8, 15, 36, 57, and 78 in the absence of disease progression or unacceptable toxicity.

ARM D (polyICLC + resiquimod) (Part I): Participants receive LPV7, tetanus peptide, poly ICLC half ID and half SC, and resiquimod topically to vaccine site immediately after vaccine administration on days 1, 8, 15, 36, 57, and 78 in the absence of disease progression or unacceptable toxicity.

ARM E (IFA + polyICLC) (Part I): Participants receive LPV7, tetanus peptide, IFA and poly ICLC half ID and half SC on days 1, 8, 15, 36, 57, and 78 in the absence of disease progression or unacceptable toxicity.

ARM E2 (IFA + polyICLC) (Part II): Participants receive LPV7, IFA, and poly ICLC half ID and half SC on days 1, 8, 15, 36, 57, and 78 in the absence of disease progression or unacceptable toxicity.

ARM F (IFA + resiquimod) (Part I): Participants receive LPV7, tetanus peptide, IFA half ID and half SC, and resiquimod topically to vaccine site immediately after vaccine administration on days 1, 8, 15, 36, 57, and 78 in the absence of disease progression or unacceptable toxicity.

ARM G (IFA + polyICLC + resiquimod) (Part I): Participants receive LPV7, tetanus peptide, poly ICLC and IFA half ID and half SC, and resiquimod topically to vaccine site immediately after vaccine administration on days 1, 8, 15, 36, 57, and 78 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 30 days, week 26, then annually for 2 years.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Virginia Cancer Center

Principal Investigator
Craig Lee Slingluff

Trial IDs

Primary ID 15931
Secondary IDs NCI-2017-02212, Mel 60
Clinicaltrials.gov ID NCT02126579