Safety Study of a Helper Peptide Vaccine Plus Adjuvant Combinations for the Treatment of Melanoma

NCT02425306 | Terminated Phase 1 Results DMC

• 1 other identifier: 17860
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates whether it is safe to administer a peptide vaccine in combination with different adjuvants. Adjuvants are substances that may boost immune responses vaccines. In this study, the adjuvants are Montanide ISA-51, polyICLC and cyclophosphamide. This study will also evaluate the effects of the combination of the peptide vaccine and the adjuvants on the immune system. The investigators will monitor these effects by performing tests in the laboratory on participants' blood, a lymph node, and tissue from the sites of vaccination.

Conditions

Melanoma

Keywords

peptide; vaccine; adjuvant; polyICLC; cyclophosphamide; Montanide ISA-51

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Adverse Events

  Treatment-related adverse events, by CTCAE v4, Dose-limiting toxicities.

  30 days after administration of the last dose of 6MHP or cyclophosphamide

• Immunogenicity-CD4+ T Cell Responses

  CD4+ T cell responses to 6 MHP: durable helper T cell response to 6MHP at 2 or more consecutive timepoints in the PBMC.

  through day 85

• Immunogenicity-modification of the Tumor Microenvironment (Part 2 Only)

  increased infiltration of CD4+ and CD8+ T lymphocytes into melanoma metastases

  through day 22

Secondary Outcomes (1)

• Immunogenicity-CD8+ T Cell Responses

  through day 85

Study Arms (4)

Arm A:6MHP + Montanide ISA-51

EXPERIMENTAL

Part 1: 200 mcg of 6MHP emulsified in Montanide ISA-51 adjuvant will be administered on 1, 8, 15, 36, 57 and 78.

Biological: 6MHP; Drug: Montanide ISA-51

Arm B:6MHP + Montanide ISA-51 + Cyclophosphamide

EXPERIMENTAL

Part 1: 200 mcg of 6MHP emulsified in Montanide ISA-51 adjuvant will be administered on 1, 8, 15, 36, 57 and 78. Cyclophosphamide (50 mg) will be taken orally once a day for 7 days followed by a 7 day rest period. This will be repeated for 5 cycles. Cycles will begin on the following days: * Day -6 (Cycle 1) * Day 8 (Cycle 2) * Day 22 (Cycle 3) * Day 36 (Cycle 4) * Day 50 (Cycle 5)

Biological: 6MHP; Drug: Montanide ISA-51; Drug: Cyclophosphamide

Arm C:6MHP + polyICLC + Montanide ISA-51

EXPERIMENTAL

Part 1: 200 mcg of 6MHP plus 1 mg of polyICLC emulsified in Montanide ISA-51 adjuvant will be administered on 1, 8, 15, 36, 57 and 78.

Biological: 6MHP; Drug: Montanide ISA-51; Drug: polyICLC

Arm D:6MHP + polyICLC + Montanide ISA-51 + Cyclophosphamide

EXPERIMENTAL

Parts 1 and 2: 200 mcg of 6MHP plus 1 mg of polyICLC emulsified in Montanide ISA-51 adjuvant will be administered on 1, 8, 15, 36, 57 and 78. Cyclophosphamide (50 mg) will be taken orally once a day for 7 days followed by a 7 day rest period. This will be repeated for 5 cycles. Cycles will begin on the following days: * Day -6 (Cycle 1) * Day 8 (Cycle 2) * Day 22 (Cycle 3) * Day 36 (Cycle 4) * Day 50 (Cycle 5)

Biological: 6MHP; Drug: Montanide ISA-51; Drug: polyICLC; Drug: Cyclophosphamide

Interventions

6MHP BIOLOGICAL

6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides

Also known as: 6 melanoma helper peptide vaccine

Arm A:6MHP + Montanide ISA-51; Arm B:6MHP + Montanide ISA-51 + Cyclophosphamide; Arm C:6MHP + polyICLC + Montanide ISA-51; Arm D:6MHP + polyICLC + Montanide ISA-51 + Cyclophosphamide

Montanide ISA-51 DRUG

Montanide ISA-51 (Incomplete Freund's Adjuvant), local adjuvant

Arm A:6MHP + Montanide ISA-51; Arm B:6MHP + Montanide ISA-51 + Cyclophosphamide; Arm C:6MHP + polyICLC + Montanide ISA-51; Arm D:6MHP + polyICLC + Montanide ISA-51 + Cyclophosphamide

polyICLC DRUG

polyICLC, local adjuvant

Arm C:6MHP + polyICLC + Montanide ISA-51; Arm D:6MHP + polyICLC + Montanide ISA-51 + Cyclophosphamide

Cyclophosphamide DRUG

Cyclophosphamide, systemic adjuvant

Arm B:6MHP + Montanide ISA-51 + Cyclophosphamide; Arm D:6MHP + polyICLC + Montanide ISA-51 + Cyclophosphamide

Eligibility Criteria

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

You may qualify if:

• Part 1 only: Participants with stage IIB, IIC, III, or IV melanoma at original diagnosis or at restaging after recurrence. Patients with high-risk stage IIA melanoma (by DecisionDx Melanoma test, Castle Biosciences, Inc,;Friendswood, TX) also may be eligible. These participants may have had cutaneous, uveal, mucosal primary melanoma, or an unknown primary melanoma. Diagnosis of melanoma must be confirmed by cytological or histological examination. Staging of cutaneous melanoma will be based on version 7 AJCC staging system.
• Part 2 only: Patients with a diagnosis of stage IIIB-IV melanoma with one or more tumor deposits accessible for biopsy and/or excision. These participants may have had cutaneous, uveal, mucosal primary melanoma, or an unknown primary melanoma. Diagnosis of melanoma must be confirmed by cytological or histological examination. Staging of cutaneous melanoma will be based on version 7 AJCC staging system.
• Patients must have adequate cutaneous, subcutaneous, soft tissue, or nodal metastases of melanoma readily accessible for biopsy
• Participants will be required to have radiological studies to rule out radiologically evident disease. Required studies include:
• Chest CT scan,
• Abdominal and pelvic CT scan, and
• Head CT scan or MRI
• PET/CT fusion scan may replace scans of the chest, abdomen, and pelvis.
• Participants who have had brain metastases will be eligible if all of the following are true:
• Each brain metastasis must have been completely removed by surgery or each unresected brain metastasis must have been treated with stereotactic radiosurgery.
• There has been no evident growth of any brain metastasis since the most recent treatment.
• No brain metastasis is \> 2 cm in diameter at the time of registration.
• The most recent surgical resections or gamma-knife therapy for malignant melanoma must have been completed ≥ 1 week and for Part 1, ≤ 6 months prior to registration.
• All participants must have:
• ECOG performance status of 0 or 1 (Appendix 3)

You may not qualify if:

• Participants who have received the following medications or treatments at any time within 4 weeks of registration:
• Chemotherapy
• Interferon (e.g. Intron-A®)
• Radiation therapy (Stereotactic radiotherapy, such as gamma knife, can be used ≥ 1 week and ≤ 6 months prior to registration)
• Allergy desensitization injections
• High doses of systemic corticosteroids, with the following qualifications and exceptions:
• In patients with adrenal or pituitary insufficiency replacement steroid doses are allowed; however, daily doses of 10 mg or more of prednisone (or equivalent) per day administered parenterally or orally are not allowed in patients with normal adrenal and pituitary function.
• Inhaled steroids (e.g.: Advair®, Flovent®, Azmacort®) are permitted at low doses (less than 500 mcg fluticasone per day, or equivalent) (76,77).
• Topical, nasal, and intra-articular corticosteroids are acceptable.
• Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)
• Interleukins (e.g. Proleukin®)
• Any investigational medication
• Targeted therapies specific for mutated BRAF or for MEK
• Participants who are currently receiving nitrosoureas or who have received this therapy within the preceding 6 weeks
• Participants who are currently receiving a checkpoint molecule blockade therapy, or who have received this therapy within the preceding 12 weeks.

Sponsors & Collaborators

• Craig L Slingluff, Jr: lead
• Ludwig Institute for Cancer Research: collaborator
• Cancer Research Institute, New York City: collaborator

Study Sites (1)

Cancer Center at the University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

montanide ISA 51; Cyclophosphamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Craig Slingluff, MD, Professor of Surgery
• Organization: University of Virginia

cls8h@virginia.edu

434-924-9311

Study Officials

• Craig L. Slingluff, Jr., MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: Director, Human Immune Therapy Center

Study Record Dates

• First Submitted: April 20, 2015
• First Posted: April 23, 2015
• Study Start: May 12, 2015
• Primary Completion: August 18, 2017
• Study Completion: January 8, 2018
• Last Updated: October 30, 2023
• Results First Posted: April 29, 2021

Record last verified: 2023-10

Locations

US (1)