- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01657591
Study of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma
Phase I Study of Escalating Doses of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Florida
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Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center and Research Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Clinical Laboratory Improvement Amendments (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-naïve 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Dose Escalation
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.
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Level -1: XL888 30 mg; Level 1: XL888 30 mg; Level 2: XL888 45 mg; Level 3: XL888 90 mg; Level 4: XL888 135 mg
Other Names:
Level -1: Vemurafenib 720 mg; Level 1: Vemurafenib 960 mg; Level 2: Vemurafenib 960 mg; Level 3: Vemurafenib 960 mg; Level 4: Vemurafenib 960 mg
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D)
Time Frame: Average of 36 weeks
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MTD and RP2D of XL888 when administered orally with vemurafenib to patients with BRAF V600 mutated melanoma, and evaluate the safety and tolerability of this combination.
Safety will be assessed by evaluation of adverse events (AEs), vital signs, electrocardiogram (ECG), laboratory tests and concomitant medications.
Adverse event terms recorded on the case report forms (CRFs) will be standardized using the Medical Dictionary for Regulatory Activities (MedDRA).
Severity grade will be defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Summaries will be directed toward treatment-emergent adverse events (TEAEs), defined as events that start or worsen after the first dose of study treatment.
TEAEs will be tabulated in accordance with system organ class and preferred term by overall incidence, worst reported severity, and relationship to study treatment.
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Average of 36 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival (PFS) Rate
Time Frame: 6 months
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Progression Free Survival at 6 months.
The median time and its 95% confidence intervals will be estimated using the Kaplan-Meier method for the same cohort.
The corresponding Kaplan-Meier curves will also be generated.
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6 months
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Overall Survival (OS) Rate
Time Frame: 1 year
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Overall Survival at 1 year.
The median time and its 95% confidence intervals will be estimated using the Kaplan-Meier method for the same cohort.
The corresponding Kaplan-Meier curves will also be generated.
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1 year
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Best Overall Response Rate (ORR)
Time Frame: 18 months
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The best overall response is the best response recorded from the start of the treatment until the end of treatment taking into account any requirement for confirmation.
In general, the patient's best response assignment will depend on findings of both target and non-target disease and will also take into consideration the appearance of new lesions.
Tumor response for all participants will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST, V1.1).
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18 months
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Zeynep Eroglu, M.D., H. Lee Moffitt Cancer Center and Research Institute
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- MCC-17013
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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