Study of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma
This is a multi-cohort, dose-escalation study of XL888 with a fixed dose of vemurafenib. New dose escalation or de-escalation cohorts will be assigned by the Principal Investigator (PI) with discussion with appropriate co-investigators once safety and tolerability is known for a given cohort in accordance to dose escalation rules. Participants will be defined to be enrolled within a cohort upon receipt of first dose of XL888/vemurafenib.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Escalating Doses of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma|
- Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) [ Time Frame: Average of 36 weeks ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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.
- Overall Response Rate (ORR) [ Time Frame: 18 months ] [ Designated as safety issue: No ]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).
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||January 2015|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
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
Other Names:Drug: Vemurafenib
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
In this study, the investigational drug XL888 will be given along with the drug vemurafenib. The investigators want to learn more about the safety and side effects of XL888 and hope to find out what dose of the drug can be given safely without serious side effects. Based on research done in a laboratory on tissue samples (cells collected from living things), the researchers think that XL888 might help to make vemurafenib work to fight cancer cells in the body for a longer period of time.
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute||Recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Leticia Tetteh 813-745-4617 firstname.lastname@example.org|
|Principal Investigator: Geoffrey Gibney, M.D.|
|Sub-Investigator: Jeffrey Weber, M.D., Ph.D.|
|Sub-Investigator: Timothy McCardle, M.D.|
|Sub-Investigator: Jane Messina, M.D.|
|Sub-Investigator: Amod Sarnaik, M.D.|
|Sub-Investigator: Keiran Smalley, Ph.D.|
|Sub-Investigator: Jonathan Zager, M.D.|
|Sub-Investigator: Vernon Sondak, M.D.|
|Principal Investigator:||Geoffrey Gibney, M.D.||H. Lee Moffitt Cancer Center and Research Institute|