Clinical Trials /

XL888 + Vemurafenib + Cobimetinib for Unresectable BRAF Mutated Stage III/IV Melanoma

NCT02721459

Description:

The main purpose of this study is to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of XL888 when administered orally with vemurafenib plus cobimetinib in participants with BRAF V600 mutated melanoma and to evaluate the safety and tolerability of this combination.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">XL888</span> With Vemurafenib Plus <span class="go-doc-concept go-doc-intervention">Cobimetinib</span> for Patients With Unresectable <span class="go-doc-concept go-doc-biomarker">BRAF</span> <span class="go-doc-concept go-doc-keyword">Mutated</span> Stage III/IV <span class="go-doc-concept go-doc-disease">Melanoma</span>

Title

  • Brief Title: XL888 With Vemurafenib Plus Cobimetinib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma
  • Official Title: Phase I Study of Escalating Doses of XL888 With Vemurafenib Plus Cobimetinib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma
  • Clinical Trial IDs

    NCT ID: NCT02721459

    ORG ID: MCC-18597

    Trial Conditions

    Melanoma

    Skin Cancer

    Trial Interventions

    Drug Synonyms Arms
    XL888 Dose Escalation
    Vemurafenib Zelboraf Dose Escalation
    Cobimetinib GDC-0973/XL518 Dose Escalation

    Trial Purpose

    The main purpose of this study is to determine the maximum tolerated dose (MTD) and
    recommended phase II dose (RP2D) of XL888 when administered orally with vemurafenib plus
    cobimetinib in participants with BRAF V600 mutated melanoma and to evaluate the safety and
    tolerability of this combination.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Dose Escalation Experimental Escalating Doses of XL888 with Vemurafenib plus Cobimetinib. XL888, Vemurafenib, Cobimetinib

    Eligibility Criteria

    Inclusion Criteria:

    - Must be 18 years of age or above. All races and ethnicities are eligible and no upper
    limit of age is specified.

    - Must have cytologically or histologically-confirmed unresectable melanoma that
    harbors a BRAF V600 E or K mutation determined by pyrosequencing assay or equivalent
    genotyping assay in a CLIA certified laboratory, meeting one of the following AJCC
    staging criteria: 1.) American Joint Committee on Cancer (AJCC) stage IV (Tany, Nany,
    M1a, b, or c); 2.) AJCC stage IIIB or IIIC with unresectable nodal/locoregional
    involvement.

    - Adequate hepatic, renal, and bone marrow function with parameters obtained within 2
    weeks prior to initiation of study treatment.

    - Eastern Cooperative Oncology Group (ECOG) performance status of 2.

    - Willing to give written informed consent per institutional guidelines and must be
    able to adhere to dose and visit schedules.

    - Negative serum pregnancy test within 7 days prior to commencement of dosing in
    premenopausal women. Women of non-childbearing potential may be included without
    serum pregnancy test if they are either surgically sterile or have been
    postmenopausal for 1 year.

    - Fertile men and women must use an effective method of contraception during treatment
    and for at least 6 months after completion of treatment as directed by their
    physician.

    - Treatment-nave and previously treated patients will be included; however, patients
    may not have received a BRAF, MEK or HSP90 inhibitor in the past.

    - May have received prior systemic and/or radiation therapy. All adverse events
    associated with prior systemic therapy or radiation therapy must have resolved to
    Grade 1 prior to start of study.

    - Must have measurable disease as defined by Response Evaluation Criteria in Solid
    Tumors (RECIST) 1.1.

    Exclusion Criteria:

    - Women who are pregnant, intend to become pregnant or are nursing.

    - Previously treated with BRAF, MEK or HSP90 inhibitor therapy.

    - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
    infection, or psychiatric illness/social situations that would limit compliance with
    study requirements.

    - HIV-positive patients on combination antiretroviral therapy.

    - Potential participants with untreated or uncontrolled brain metastases or evidence of
    leptomeningeal disease. Patients with asymptomatic brain metastases or previously
    treated brain metastases that are stable (i.e., not requiring corticosteroids) at the
    time of study start will be eligible.

    - Previous malignancy is not an exclusion provided that the other malignancy is
    considered under control, patient is not on concomitant anti-cancer drug therapy, and
    target lesions from melanoma are clearly defined for response assessment.

    - History of malabsorption or other condition that would interfere with absorption of
    study drugs.

    - The following foods/supplements are prohibited at least 7 days prior to initiation of
    and during study treatment: St. John's wort or hyperforin (potent cytochrome P450
    CYP3A4 enzyme inducer); Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme
    inhibitor).

    - Ocular: History of or evidence of retinal pathology on ophthalmologic examination
    that is considered a risk factor for neurosensory retinal detachment, RVO (retinal
    vein occlusion), or neovascular macular degeneration.

    - Cardiac: History of clinically significant cardiac dysfunction.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum Tolerated Dose (MTD)

    Secondary Outcome Measures

    Trial Keywords

    unresectable melanoma

    stage III melanoma

    stage IV melanoma

    AJCC melanoma staging

    American Joint Committee on Cancer (AJCC)

    BRAF V600 E mutation

    BRAF V600 K mutation