Clinical Trials /

Study of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma

NCT01657591

Description:

This is a multi-cohort, dose-escalation study of XL888 with a fixed dose of vemurafenib. New dose escalation or de-escalation cohorts will be assigned by the Principal Investigator (PI) with discussion with appropriate co-investigators once safety and tolerability is known for a given cohort in accordance to dose escalation rules. Participants will be defined to be enrolled within a cohort upon receipt of first dose of XL888/vemurafenib.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Study of <span class="go-doc-concept go-doc-intervention">XL888</span> With Vemurafenib 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: Study of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma
  • Official Title: Phase I Study of Escalating Doses of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma
  • Clinical Trial IDs

    NCT ID: NCT01657591

    ORG ID: MCC-17013

    Trial Conditions

    Melanoma

    Trial Interventions

    Drug Synonyms Arms
    XL888 molecule inhibitor, Hsp90 inhibitor, EXEL-4888, EXEL-04354888 Dose Escalation
    Vemurafenib Zelobraf , PLX-4032, RG 7204, RO5185426 Dose Escalation

    Trial Purpose

    This is a multi-cohort, dose-escalation study of XL888 with a fixed dose of vemurafenib. New
    dose escalation or de-escalation cohorts will be assigned by the Principal Investigator (PI)
    with discussion with appropriate co-investigators once safety and tolerability is known for
    a given cohort in accordance to dose escalation rules. Participants will be defined to be
    enrolled within a cohort upon receipt of first dose of XL888/vemurafenib.

    Detailed Description

    In this study, the investigational drug XL888 will be given along with the drug vemurafenib.
    The investigators want to learn more about the safety and side effects of XL888 and hope to
    find out what dose of the drug can be given safely without serious side effects. Based on
    research done in a laboratory on tissue samples (cells collected from living things), the
    researchers think that XL888 might help to make vemurafenib work to fight cancer cells in
    the body for a longer period of time.

    Trial Arms

    Name Type Description Interventions
    Dose Escalation Experimental The treatment period will include dosing (taking a certain amount on a regular schedule) with vemurafenib along with the study drug, XL888. Everyone in the study will receive both drugs, but the XL888 will be given at different doses (different amounts). Everyone in this study will be given vemurafenib at the standard dose (the amount of the drug that is given as standard treatment) of 960 milligrams (mg) twice per day, unless the first people in the study have severe side effects when taking the lowest dose of XL888 along with vemurafenib. If that happens, the next people in the study may be given a lower dose of vemurafenib (720 mg twice per day) along with the lowest dose of XL888. XL888, Vemurafenib

    Eligibility Criteria

    Inclusion Criteria:

    - 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
    American Joint Committee on Cancer (AJCC) staging criteria:

    - AJCC Stage IV (Tany, Nany, M1a, b, or c)

    - AJCC Stage III B or C with unresectable nodal/locoregional involvement

    - Adequate hepatic, renal, and bone marrow function as defined by the following
    parameters obtained within 2 weeks prior to initiation of study treatment:

    - Hematologic Criteria: leukocytes 3,000/mcL; absolute neutrophil count
    1,500/mcL; platelets 100,000/mcL

    - Renal Criteria: serum creatinine within normal institutional limits or a
    creatinine clearance 60 mL/min for patients with creatinine levels above
    institutional normal

    - Hepatic Criteria: aspartate aminotransferase (AST)/alanine transaminase (ALT)
    2.5 X institutional upper limit of normal; if liver metastasis present, then
    AST/ALT may be less than or equal to 5 times the upper limit of normal

    - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

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

    - Female and male participants must agree to use a medically acceptable method of birth
    control prior to screening and agree to continue its use throughout the study.
    Females of childbearing potential should be counseled in the appropriate use of birth
    control while on this study.

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

    - Patients must be at least 4 weeks from any prior systemic therapy (6 weeks for
    nitrosoureas or mitomycin C), surgery or radiation.

    - Must have measurable disease as defined by RECIST 1.1

    Exclusion Criteria:

    - Females who are pregnant, intend to become pregnant or are nursing. Females with
    child-bearing potential must have a negative pregnancy test within one week of
    enrollment.

    - Previously treated with BRAF or HSP90 inhibitor therapy

    - Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
    nitrosoureas or mitomycin C) prior to entering the study or those who have not
    recovered from adverse events due to agents administered more than 4 weeks earlier.

    - Patients who are receiving any other investigational agents.

    - History of allergic reactions attributed to compounds of similar chemical or biologic
    composition (i.e. ethanol) to XL888 or vemurafenib (i.e., ethanol).

    - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
    infection, symptomatic congestive heart failure, unstable angina pectoris,
    uncontrolled or symptomatic cardiac arrhythmia, or psychiatric illness/social
    situations that would limit compliance with study requirements

    - HIV-positive patients on combination antiretroviral therapy are ineligible because of
    the potential for pharmacokinetic interactions with XL888 and vemurafenib.

    - Untreated or uncontrolled brain metastases or evidence of leptomeningeal disease.
    Brain metastases that have been appropriately treated with radiation and/or surgery
    will be allowed as long as the central nervous system (CNS) disease has been stable
    for at least 4 weeks post-treatment.

    - Must be at least 3 years from any prior malignancy and have no evidence of the
    malignancy at the time of enrollment. Patients with adequately treated squamous cell
    or basal cell carcinomas of the skin, multiple primary melanomas, or any carcinoma in
    situ will be allowed.

    - Corrected QT interval (QTc) greater than 460 ms at baseline

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D)

    Secondary Outcome Measures

    Progression Free Survival (PFS) Rate

    Overall Survival (OS) Rate

    Best Overall Response Rate (ORR)

    Trial Keywords

    skin cancer

    unresectable

    BRAF