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Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies

NCT01781429

Description:

This open-label, multi-center Phase 1/2 study will assess the safety, pharmacokinetics, and pharmacodynamics of escalating doses of BVD-523 in patients with advanced malignancies. The study also seeks to demonstrate target modulation and early signs of clinical response in select patient populations.

Related Conditions:
  • Cancer
  • Melanoma
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of <span class="go-doc-concept go-doc-intervention">BVD-523</span> in Patients With Advanced Malignancies

Title

  • Brief Title: Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies
  • Official Title: Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies
  • Clinical Trial IDs

    NCT ID: NCT01781429

    ORG ID: BVD-523-01

    NCI ID: BVD-523-01

    Trial Conditions

    Advanced Solid Tumors

    Trial Interventions

    Drug Synonyms Arms
    BVD-523 BVD-523

    Trial Purpose

    This open-label, multi-center Phase 1/2 study will assess the safety, pharmacokinetics, and
    pharmacodynamics of escalating doses of BVD-523 in patients with advanced malignancies. The
    study also seeks to demonstrate target modulation and early signs of clinical response in
    select patient populations.

    Detailed Description

    The study is being performed to assess the safety and tolerability of BVD-523

    In Part 1 of the study, an accelerated dose escalation plan will be used to establish dose
    limiting toxicities, maximum tolerated dose, and the recommended Phase 2 dose.

    In Part 2 of the study, additional patients with particular tumor types and/or cancers
    harboring specific genetic mutations will be recruited for treatment at the Recommended
    Phase 2 Dose. Patients may also be assessed pharmacodynamic measures in healthy or malignant
    tissues, using biomarker assays for phosphorylation, cytotoxic or cytostatic measures.

    Trial Arms

    Name Type Description Interventions
    BVD-523 Experimental BVD-523

    Eligibility Criteria

    Inclusion Criteria:

    - Patients with metastatic or advanced-stage malignant tumor. Patients may have
    received up to 2 prior lines of chemotherapy for their metastatic disease

    - ECOG score of 0 or 1

    - Predicted life expectancy of 3 months

    - Adequate bone marrow, liver and renal function renal function

    - Adequate cardiac function

    - For women: Negative pregnancy test for females of child-bearing potential; must be
    surgically sterile, postmenopausal, or compliant with a contraceptive regimen during
    and for 3 months after the treatment period

    - For men: Must be surgically sterile, or compliant with a contraceptive regimen during
    and for 3 months after the treatment period

    - For Part 2 of the Study only, patients must have measurable disease by RECIST 1.1 and
    be in one of the the groups below. Patients in groups 1, 2, 4, 5 and 6 may not have
    been previously treated with BRAF and/or MEK inhibitors

    - Group 1: Patients with BRAF mutated cancer, except those with colorectal or
    non-small cell lung cancers

    - Group 2: Patients with BRAF mutated colorectal cancer

    - Group 3: Patients with BRAF mutated melanoma who have progressed on, or are
    refractory to BRAF and/or MEK inhibitors

    - Group 4: Patients with NRAS mutated melanoma

    - Group 5: Patients with MEK mutated cancer

    - Group 6: Patients with BRAF mutated non-small cell lung cancer

    Exclusion Criteria:

    - Gastrointestinal condition which could impair absorption of study medication

    - Uncontrolled or severe intercurrent medical condition

    - Known uncontrolled brain metastases. Stable brain metastases either treated or being
    treated with a stable dose of steroids/anticonvulsants

    - Any cancer-directed therapy (chemotherapy, radiotherapy, hormonal therapy, biologic
    or immunotherapy, etc.) within 28 days or 5 half-lives, whichever is shorter

    - Major surgery within 4 weeks prior to first dose

    - Any use of an investigational drug within 28 days or 5 half-lives (whichever is
    shorter) prior to the first dose of BVD-523.

    - Pregnant or breast-feeding women

    - Any evidence of serious active infections

    - Any important medical illness or abnormal laboratory finding that would increase the
    risk of participating in this study

    - A history or current evidence/risk of retinal vein occlusion or central serous
    retinopathy

    - Concurrent therapy with any other investigational agent

    - Concomitant malignancies or previous malignancies with less than 2 years disease-free
    interval at the time of enrollment

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Determination of recommended phase 2 dose of BVD-523 determined by dose-limiting toxicities.

    Secondary Outcome Measures

    Characterization of the time versus plasma concentration profiles of BVD-523 and selected metabolites.

    Clinical evidence of tumor response assessed by physical or radiological exam.

    Trial Keywords