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

Primary Purpose

Melanoma, Skin Cancer

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
XL888
Vemurafenib
Cobimetinib
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • H. Lee Moffitt Cancer Center and Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dose Escalation

Arm Description

Escalating Doses of XL888 with Vemurafenib plus Cobimetinib.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
March 23, 2016
Last Updated
July 28, 2023
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Exelixis, Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02721459
Brief Title
XL888 + Vemurafenib + Cobimetinib for 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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 7, 2016 (Actual)
Primary Completion Date
October 31, 2019 (Actual)
Study Completion Date
October 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Exelixis, Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation
Arm Type
Experimental
Arm Description
Escalating Doses of XL888 with Vemurafenib plus Cobimetinib.
Intervention Type
Drug
Intervention Name(s)
XL888
Other Intervention Name(s)
HSP90 inhibitor
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Vemurafenib
Other Intervention Name(s)
Zelboraf ®
Intervention Description
Vemurafenib 720 mg by mouth twice a day (BID)
Intervention Type
Drug
Intervention Name(s)
Cobimetinib
Other Intervention Name(s)
GDC-0973/XL518
Intervention Description
Cobimetinib 40 mg by mouth once daily (QD). Administered 3 weeks on, 1 week off.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Description
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.
Time Frame
Up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zeynep Eroglu, M.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States

12. IPD Sharing Statement

Links:
URL
https://moffitt.org/clinical-trials-research/
Description
Moffitt Cancer Center Clinical Trials website

Learn more about this trial

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

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