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

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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 mutation determined by pyrosequencing assay or equivalent genotyping assay in a Clinical Laboratory Improvement Amendments (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 4 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-naïve and previously treated patients will be included; however, patients may not have received a BRAF, Mitogen Activated Kinase (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, retinal vein occlusion (RVO), or neovascular macular degeneration.
  • - Cardiac: History of clinically significant cardiac dysfunction.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT02721459
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

H. Lee Moffitt Cancer Center and Research Institute
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Zeynep Eroglu, M.D.
Principal Investigator Affiliation H. Lee Moffitt Cancer Center and Research Institute
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Melanoma, Skin Cancer
Study Website: View Trial Website

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Tampa, Florida

Status

Recruiting

Address

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612

Site Contact

813-745-4617

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