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

NCT02721459 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: MCC-18597
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Melanoma; Skin Cancer

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  The maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of XL888 when administered orally with vemurafenib plus cobimetinib in patients with BRAF V600 mutated melanoma.

  Up to 12 months

Study Arms (1)

Dose Escalation

EXPERIMENTAL

Escalating Doses of XL888 with Vemurafenib plus Cobimetinib.

Drug: XL888; Drug: Vemurafenib; Drug: Cobimetinib

Interventions

XL888 DRUG

Level 1: XL888 30 mg by mouth (PO) twice weekly (BIW). Level 2: XL888 45 mg PO BIW. Level 3: XL888 60 mg PO BIW. Level 4: XL888 90 mg PO BIW.

Also known as: HSP90 inhibitor

Dose Escalation

Vemurafenib DRUG

Vemurafenib 720 mg by mouth twice a day (BID)

Also known as: Zelboraf ®

Dose Escalation

Cobimetinib DRUG

Cobimetinib 40 mg by mouth once daily (QD). Administered 3 weeks on, 1 week off.

Also known as: GDC-0973/XL518

Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Exelixis: collaborator
• Genentech, Inc.: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

Hsp90 inhibitor KU757; Vemurafenib; cobimetinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Zeynep Eroglu, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2016
• First Posted: March 29, 2016
• Study Start: September 7, 2016
• Primary Completion: October 31, 2019
• Study Completion (Estimated): November 4, 2026
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

US (1)