A Clinical Trial to Evaluate a Melanoma Helper Peptide Vaccine Plus Dabrafenib and Trametinib

NCT02382549 | Terminated Early Phase 1 DMC

• 2 other identifiers: 17700R01CA178846
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates whether it is safe to administer a helper peptide vaccine with BRAF inhibitor and MEK inhibitor therapy. This study will also evaluate the effects of the combination of the peptide vaccine and BRAF inhibitors/MEK inhibitors on the immune system. We will monitor these effects by performing tests in the laboratory on participants' blood and tumor samples.

Conditions

Melanoma

Keywords

vaccine; peptide; dabrafenib; trametinib; Montanide ISA-51; MEKINIST; Tafinlar; BRAF inhibitor; MEK inhibitor; BRAFi; MEKi; encorafenib; binimetinib; BRAFTOVI; MEKTOVI; vemurafenib; Zeldoraf; cobimetinib; Cotellic; 6MHP

Outcome Measures

Primary Outcomes (2)

• Adverse event profile for the combination of BRAFi, MEKi, and 6MHP

  30 days after the last vaccination with 6MHP

• CD4+ T cell responses in the blood

  CD4+ T cell responses to the peptide vaccine

  through day 85

Secondary Outcomes (2)

• An evaluation of the infiltration of T cells into melanoma metastases pre and post-vaccination.

  pre-vaccine and day 22

• Antibody responses against 6MHP

  through day 85

Study Arms (1)

6MHP and MEKi and BRAFi

EXPERIMENTAL

The vaccine drug product, 6MHP, consists of 6 class II MHC-restricted peptides derived from melanoma proteins. Each vaccine consists of 200 mcg of each of the six peptides. An aqueous solution of vaccine is mixed 1/1 with Montanide ISA-51 to form water-in-oil emulsions. Vaccines are administered days 1, 8, 15, 36, 57, 78. All peptide vaccines are administered intradermally and subcutaneously. A selective BRAF inhibitor and a selective MEK inhibitor will be administered in accordance with the prescribing information.

Drug: BRAF inhibitor; Biological: 6MHP; Drug: MEK inhibitor

Interventions

BRAF inhibitor DRUG

BRAF inhibitor

6MHP and MEKi and BRAFi

6MHP BIOLOGICAL

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

Also known as: 6 melanoma helper peptide vaccine

6MHP and MEKi and BRAFi

MEK inhibitor DRUG

MEK Inhibitor

6MHP and MEKi and BRAFi

Eligibility Criteria

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

You may qualify if:

• Cohort 1 (Advanced): Measurable stage IIIB, IIIC, IIID or IV melanoma with clinical or radiological evidence of disease. These participants may have had cutaneous, uveal, mucosal primary melanoma, or an unknown primary melanoma. Staging must be confirmed by cytological or histological examination. Staging of cutaneous melanoma will be based on the revised AJCC 8th Edition staging system (Appendix 2) 66.
• Cohort 2 (Neo-adjuvant): Resectable stage IIIB, IIIC, IIID, or IV melanoma at initial presentation or subsequent recurrence. These participants have disease amenable to complete surgical resection at the time of enrollment in the study. The resectable disease does not need to be measurable by RECIST v1.1 criteria.
• Cohort 3 (Adjuvant): Participants with stage IIIA, IIIB, IIIC, IIID or IV melanoma resected to no evidence of disease. Participants must initiate therapy within 12 weeks of last surgical resection and within 12 weeks of being rendered clinically free of disease by non-surgical approaches Patients that have undergone ablative therapy to a metastatic lesion (e.g. GKRS, radiofrequency ablation) that manifest no additional sites of disease at enrollment are eligible for treatment on cohort 3
• Participants must be eligible to be treated with BRAF inhibitor and MEK inhibitor combination.
• Participants with prior therapy with targeted therapies specific for mutated BRAF including BRAF and/or MEK inhibitors are eligible provided that there was clinical benefit to prior therapy with these agents as judged by the treating physician. There must be an interval of at least 6 months from the last BRAF/MEK therapy and enrollment in this clinical study
• Participants will be required to have radiological studies at baseline to establish measurable disease for cohort 1 or to prove lack of distant metastases for cohorts 2 and 3. Required studies include:
• Chest CT scan,
• Abdominal and pelvic CT scan, and
• Head CT scan or MRI
• Participants in cohorst 1 \& 2 who have metastatic melanoma safely available for biopsy pretreatment and on day 22 must consent to having those biopsies. These metastases may be in nodes, skin, soft tissue, liver, or other sites that can be accessed by needle biopsy, incisional or excisional biopsy, with or without image guidance.
• 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 or systemic immunotherapy
• There has been no evident growth of any brain metastasis since the most recent treatment if the last treatment is \>4 weeks prior to enrollment
• No brain metastasis is \> 2 cm in diameter at the time of registration
• Neurologic symptoms have returned to baseline off steroids,

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
• Corticosteroids, administered transdermally, parenterally or orally. Inhaled steroids (e.g.: Advair®, Flovent®, Azmacort®) are not permitted. Topical corticosteroids are acceptable.
• Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)
• Interleukins (e.g. Proleukin®)
• Any investigational medication
• HIV positivity or evidence of active Hepatitis C virus.
• Participants who are currently receiving nitrosoureas or who have received this therapy 6 weeks prior to registration
• Participants who are currently receiving a checkpoint molecule blockade therapy, or who have received this therapy within 3weeks prior to registration.
• Participants with known or suspected allergies to any component of the vaccine.
• Participants may not have been vaccinated previously with any of the synthetic peptides included in this protocol. Participants who have received vaccinations containing agents other than the synthetic peptides included in this protocol and have recurred during or after administration of the vaccine will be eligible to enroll 12 weeks following their last vaccination.
• Pregnancy.

Sponsors & Collaborators

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

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

MEK inhibitor I

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

Study Officials

• Elizabeth Gaughan, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

• Craig L. Slingluff, Jr., MD

  University of Virginia

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 6, 2015
• Study Start: April 1, 2016
• Primary Completion: February 28, 2022
• Study Completion: February 28, 2022
• Last Updated: December 12, 2023

Record last verified: 2023-12

Locations

US (1)