Clinical Trials /

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

NCT02382549

Description:

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, a lymph node, and tumor samples.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Clinical Trial to Evaluate a Melanoma Helper Peptide Vaccine Plus Dabrafenib and Trametinib
  • Official Title: A Trial to Evaluate the Safety, Immunogenicity, and Clinical Activity of a Helper Peptide Vaccine Plus Combination of BRAF Inhibition and MEK Inhibition (Mel61)

Clinical Trial IDs

  • ORG STUDY ID: 17700
  • SECONDARY ID: R01CA178846
  • NCT ID: NCT02382549

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
dabrafenibTafinlar6MHP and dabrafenib and trametinib
6MHP6 melanoma helper peptide vaccine6MHP and dabrafenib and trametinib
TrametinibMEKINIST6MHP and dabrafenib and trametinib

Purpose

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, a lymph node, and tumor samples.

Trial Arms

NameTypeDescriptionInterventions
6MHP and dabrafenib and trametinibExperimentalThe 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.
  • dabrafenib
  • 6MHP
  • Trametinib

Eligibility Criteria

        Inclusion Criteria:

          -  Participants with measurable stage IIIB, IIIC, or IV melanoma that have 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 staging system.

          -  Participants must be eligible to be treated with BRAF inhibitor and MEK inhibitor
             combination.

          -  Participants will be required to have radiological studies to define radiologically
             evident disease. Required studies include:

               -  Chest CT scan,

               -  Abdominal and pelvic CT scan, and

               -  Head CT scan or MRI

          -  Participants who have metastatic melanoma 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:

               -  The total number of brain metastases ever ≤ 3

               -  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 ≤ 6 months prior to registration.

          -  ECOG performance status of 0 or 1

          -  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 ≤ 7.5%

               -  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

               -  Targeted therapies specific for mutated BRAF

               -  MEK inhibitor

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse event profile for the combination of dabrafenib, trametinib, and 6MHP
Time Frame:30 days after the last vaccination with 6MHP
Safety Issue:
Description:CD4+ T cell responses to the peptide vaccine

Secondary Outcome Measures

Measure:An evaluation of the infiltration of T cells into melanoma metastases pre and post-vaccination.
Time Frame:pre-vaccine and day 22
Safety Issue:
Description:
Measure:Antibody responses against 6MHP
Time Frame:through day 85
Safety Issue:
Description:An evaluation of the development of antibdoy responses following vaccination

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Craig L Slingluff, Jr

Trial Keywords

  • vaccine
  • peptide
  • dabrafenib
  • trametinib
  • Montanide ISA-51
  • MEKINIST
  • Tafinlar

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