Study of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma
|ClinicalTrials.gov Identifier: NCT01657591|
Recruitment Status : Active, not recruiting
First Posted : August 6, 2012
Last Update Posted : June 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Melanoma||Drug: XL888 Drug: Vemurafenib||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of Escalating Doses of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma|
|Actual Study Start Date :||July 27, 2012|
|Actual Primary Completion Date :||September 20, 2016|
|Estimated Study Completion Date :||June 2019|
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.
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
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
- Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) [ Time Frame: Average of 36 weeks ]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.
- Progression Free Survival (PFS) Rate [ Time Frame: 6 months ]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.
- Overall Survival (OS) Rate [ Time Frame: 1 year ]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.
- Best Overall Response Rate (ORR) [ Time Frame: 18 months ]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).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01657591
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Zeynep Eroglu, M.D.||H. Lee Moffitt Cancer Center and Research Institute|