Clinical Trials /

Phase 1 Safety and Tolerability of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone

NCT02027961

Description:

The purpose of this study is to determine the maximum tolerated dose and characterize the safety profile of durvalumab (MEDI4736) in combination with dabrafenib and trametinib or with trametinib alone in participants with metastatic or unresectable melanoma with BRAF-mutation positive or wild-type (WT) BRAF, respectively.

Related Conditions:
  • Melanoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Phase 1 Safety and Tolerability of MEDI4736 in Combination With <span class="go-doc-concept go-doc-intervention">Dabrafenib</span> and <span class="go-doc-concept go-doc-intervention">Trametinib</span> or With <span class="go-doc-concept go-doc-intervention">Trametinib</span> Alone

Title

  • Brief Title: Phase 1 Safety and Tolerability of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone
  • Official Title: A Phase 1 Open-label Study of Safety and Tolerability of MEDI4736 in Subjects With Metastatic or Unresectable Melanoma in Combination With Dabrafenib and Trametinib or With Trametinib Alone
  • Clinical Trial IDs

    NCT ID: NCT02027961

    ORG ID: CD-ON-MEDI4736-1161

    Trial Conditions

    Melanoma

    Trial Interventions

    Drug Synonyms Arms
    Dabrafenib Cohort A
    Trametinib Cohort A, Cohort B, Cohort C

    Trial Purpose

    The purpose of this study is to determine the maximum tolerated dose and the safety profile
    of MEDI4736 in combination with dabrafenib and trametinib or with trametinib alone in
    subjects with metastatic or unresectable melanoma with BRAF-mutation positive or Wild Type
    BRAF, respectively.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Cohort A Experimental Dabrafenib/Trametinib/MEDI4736 Dabrafenib, Trametinib
    Cohort B Experimental Trametinib/MEDI4736 Trametinib
    Cohort C Experimental Trametinib/MEDI4736 Trametinib

    Eligibility Criteria

    Inclusion Criteria:

    - Adults >/= 18 years old

    - Histologically confirmed cutaneous melanoma that is either Stage IIIc (unresectable)
    or Stage IV (metastatic) and determined to be BRAF V600E or V600K mutation-positive
    (cohort A) or mutation-negative (cohorts B and C)

    - ECOG performance status of 0 or 1

    - Measurable disease by radiographic or physical examination

    - Adequate organ and marrow function

    - Willingness to provide consent for biopsies positive or BRAF WT measurable disease,
    Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate
    organ and marrow function

    Exclusion Criteria:

    - Prior treatment with a BRAF inhibitor or MEK inhibitor

    - Any prior Grade 3 immune-related adverse event while receiving immunotherapy

    - Active or prior documented autoimmune disease within the past 2 years

    - History of or current risk for retinal vein occlusion (RVO) or central serous
    retinopathy (CSR)

    - History of or current cardiovascular risk including myocardial infarction, Class II
    congestive heart failure, uncontrolled arrhythmias, or refractory hypertension

    - Active, untreated CNS metastases

    - Women who are pregnant or lactating

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum Tolerated Dose/Safety

    Secondary Outcome Measures

    Antitumor Activity

    Antitumor Activity

    Pharmacokinetic of MEDI4736

    Pharmacokinetic of MEDI4736

    Immunogenicity of MEDI4736

    Trial Keywords

    Metastatic or Unresectable Melanoma, MEDI4736, dafrafenib, trametinib, BRAF-mutation positive, wild-type BRAF, PD-L1, PD-1