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A Clinical Trial to Evaluate a Melanoma Helper Peptide Vaccine Plus Dabrafenib and Trametinib (Mel61)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02382549
Recruitment Status : Recruiting
First Posted : March 6, 2015
Last Update Posted : July 16, 2020
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Craig L Slingluff, Jr, University of Virginia

Brief Summary:
This study evaluates whether it is safe to administer a helper peptide vaccine with dabrafenib and trametinib. This study will also evaluate the effects of the combination of the peptide vaccine and dabrafenib and trametinib on the immune system. We will monitor these effects by performing tests in the laboratory on participants' blood and tumor samples.

Condition or disease Intervention/treatment Phase
Melanoma Drug: dabrafenib Biological: 6MHP Drug: Trametinib Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : April 2016
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: 6MHP and dabrafenib and trametinib

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.

Dabrafenib is a small molecular BRAF inhibitor and will be administered in accordance with the prescribing information: 150 mg orally twice daily taken at least 1 hour before or at least 2 hours after a meal; the doses will be approximately 12 hours apart. Trametinib is a small molecular MEK1 and MEK2 inhibitor and will be administered in accordance with the prescribing information: 2 mg orally once daily taken at least 1 hour before or at least 2 hours after a meal. The medication will be taken at the same time each day with either the morning or evening dose of dabrafenib.

Drug: dabrafenib
Braf inhibitor
Other Name: Tafinlar

Biological: 6MHP
6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides
Other Name: 6 melanoma helper peptide vaccine

Drug: Trametinib
MEK1 AND MEK2 inhibitor
Other Name: MEKINIST

Primary Outcome Measures :
  1. Adverse event profile for the combination of dabrafenib, trametinib, and 6MHP [ Time Frame: 30 days after the last vaccination with 6MHP ]
  2. CD4+ T cell responses in the blood [ Time Frame: through day 85 ]
    CD4+ T cell responses to the peptide vaccine

Secondary Outcome Measures :
  1. An evaluation of the infiltration of T cells into melanoma metastases pre and post-vaccination. [ Time Frame: pre-vaccine and day 22 ]
  2. Antibody responses against 6MHP [ Time Frame: through day 85 ]
    An evaluation of the development of antibdoy responses following vaccination

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

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.
  • 3.1.6 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,
    • Subjects are not using steroids for at least 7 days prior to registration.
    • The most recent surgical resections or gamma-knife therapy for malignant melanoma must have been completed ≥ 1 week prior to registration
  • ECOG performance status of 0-2
  • Participants must have the ability and willingness to give informed consent
  • Laboratory parameters as follows:

    • ANC > 1000/mm3
    • Platelets > 100,000/mm3
    • Hgb > 9 g/dL
    • HgB-A1c ≤ 8.5%
    • AST and 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
  • Age 18 years or older at registration
  • Participants must have at least two intact (undissected) axillary and/or inguinal lymph node basins

Exclusion Criteria:

  • 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.
  • Female participants must not be breastfeeding
  • Participants in whom there is a medical contraindication or potential problem in complying with the requirements of the protocol in the opinion of the investigator.
  • Participants classified according to the New York Heart Association classification as having Class III or IV heart disease.
  • Participants with uncontrolled diabetes, defined as having a HgB-A1c greater than 7.5%.
  • 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.
  • Participants who have another cancer diagnosis, except that the following diagnoses will be allowed:

    • squamous cell cancer of the skin without known metastasis
    • basal cell cancer of the skin without known metastasis
    • carcinoma in situ of the breast (DCIS or LCIS)
    • carcinoma in situ of the cervix
    • any cancer without distant metastasis that has been treated successfully, without evidence of recurrence or metastasis for over 3 years
  • Participants with known addiction to alcohol or drugs who are actively taking those agents, or participants with recent (within 1 year of registration) or ongoing illicit IV drug use.
  • Body weight < 110 pounds
  • Participants with a known history of glucose-6-phosphate dehydrogenase deficiency.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02382549

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Contact: Rupert Egan, MS 434-982-1901
Contact: Rachael Reed, BS 434-982-6584

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United States, Virginia
Cancer Center at the University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
Craig L Slingluff, Jr
National Cancer Institute (NCI)
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Principal Investigator: Elizabeth Gaughan, MD University of Virginia
Study Director: Craig L. Slingluff, Jr., MD University of Virginia
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Responsible Party: Craig L Slingluff, Jr, Professor of Surgery and Director, Human Immune Therapy Center, University of Virginia Identifier: NCT02382549    
Other Study ID Numbers: 17700
R01CA178846 ( U.S. NIH Grant/Contract )
First Posted: March 6, 2015    Key Record Dates
Last Update Posted: July 16, 2020
Last Verified: July 2020
Keywords provided by Craig L Slingluff, Jr, University of Virginia:
Montanide ISA-51
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action