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

This study is currently recruiting participants.
Verified December 2017 by H. Lee Moffitt Cancer Center and Research Institute
Sponsor:
ClinicalTrials.gov Identifier:
NCT02721459
First Posted: March 29, 2016
Last Update Posted: December 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Exelixis
Genentech, Inc.
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
  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.

Condition Intervention Phase
Melanoma Skin Cancer Drug: XL888 Drug: Vemurafenib Drug: Cobimetinib Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Escalating Doses of XL888 With Vemurafenib Plus Cobimetinib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: Up to 12 months ]
    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.


Estimated Enrollment: 36
Actual Study Start Date: August 11, 2016
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation
Escalating Doses of XL888 with Vemurafenib plus Cobimetinib.
Drug: XL888

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.

Other Name: HSP90 inhibitor
Drug: Vemurafenib
Vemurafenib 720 mg by mouth twice a day (BID)
Other Name: Zelboraf ®
Drug: Cobimetinib
Cobimetinib 40 mg by mouth once daily (QD). Administered 3 weeks on, 1 week off.
Other Name: GDC-0973/XL518

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02721459


Contacts
Contact: Leticia Tetteh 813-745-4617 leticia.tetteh@moffitt.org
Contact: Zeynep Eroglu, M.D. 813-745-7488 zeynep.eroglu@moffitt.org

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Principal Investigator: Zeynep Eroglu, M.D.         
Sub-Investigator: Andrew Brohl, M.D.         
Sub-Investigator: Nikhil Khushalani, M.D.         
Sub-Investigator: Joseph Markowitz, M.D., Ph.D.         
Sub-Investigator: Amod Sarnaik, M.D.         
Sub-Investigator: Vernon Sondak, M.D.         
Sub-Investigator: Jonathan Zager, M.D.         
Sub-Investigator: Trevor Rose, M.D.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Exelixis
Genentech, Inc.
Investigators
Principal Investigator: Zeynep Eroglu, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT02721459     History of Changes
Other Study ID Numbers: MCC-18597
First Submitted: March 23, 2016
First Posted: March 29, 2016
Last Update Posted: December 14, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
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

Additional relevant MeSH terms:
Melanoma
Skin Neoplasms
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
Vemurafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action