Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Gastrointestinal Agents

Dabrafenib

Vemurafenib

Lactitol

Protein Kinase Inhibitors

Enzyme Inhibitors

150 mg oral dabrafenib twice a day until disease progression, death, or unacceptable adverse events.

Phase I is 3+3 dose escalation study to identify the recommended phase 2 dose (RP2D)

Dose Level -1: BKM120 60 mg daily, Vemurafenib 480 mg bid

Dose Level 1: BKM120 60 mg daily, Vemurafenib 720 mg bid

Dose Level 2: BKM120 80 mg daiy, Vemurafenib 720 mg bid

Dose Level 3: BKM120 100 mg daiy, Vemurafenib 720 mg bid

Dose Level 4: BKM120 100 mg daiy, Vemurafenib 960 mg bid

Phase II is a single-stage, single arm prospective trial: patients will receive BKM120 and vemurafenib at the RP2D

BKM120 Combined with Vemurafenib (PLX4032)

This is a phase 1/2 clinical trial with the goal of determining whether the addition of the investigational agent BKM120 to vemurafenib will lead to improved 6-month progression-free survival in patients with BRAFV600E/K mutant melanoma.

The phase 1 portion of this trial is a dose escalation study; the phase 2 portion is a single-stage, single arm prospective clinical trial. All patients will receive continuous doses of vemurafenib twice a day and BKM120 once a day.

In the phase 1 portion of the study, there will be a 7 day lead-in period to allow for single dose pharmacokinetic analysis of BKM120 alone. Cycle 1 (28 days) is the dose-limiting toxicity (DLT) period. During phase 1, vemurafenib and BKM120 doses will be escalated using a standard 3+3 dose escalation scheme with the goal of identifying the recommended phase 2 dose.

In the phase 2 portion of the study, patients will receive continuous doses of vemurafenib and BKM120 starting on day 1 of the first cycle. In the phase 2 portion of the study, patients will receive vemurafenib and BKM120 at the recommended phase 2 dose.

BKM120 Combined With Vemurafenib (PLX4032) in BRAFV600E/K Mutant Advanced Melanoma

A Phase 1/2 Trial of BKM120 Combined With Vemurafenib (PLX4032) in BRAFV600E/K Mutant Advanced Melanoma (Novartis Study Number CBKM120ZUS21T)

RP2D determined by maximum tolerated dose (MTD), post-dose-limiting toxicity (DLT) period toxicity, and pharmacokinetic data

6 month progression-free survival rate (PFS6) determined by tumor assessments, clinical tests and laboratory tests

Objective response rate determined by tumor assessments, clinical tests and laboratory tests.

Determined by clinical and laboratory tests, and adverse events (AE) assessments

PTEN expression associated with better PFS determined by laboratory tests.

Greater reduction in PI3K-pathway signaling associated with better PFS determined by laboratory tests and tumor assessments.

Responding tumors lack gene expression signatures of PI3K pathway activation, and progressing tumors demonstrate gene expression signatures of PI3K pathway activation - determined by laboratory tests and tumor assessments.

Responding tumors lack gene expression signatures of MAPK pathway activation, and progressing tumors demonstrate gene expression signatures of MAPK pathway activation - determined by laboratory tests and tumor assessments.

Novartis

University of California, San Francisco

Assistant Clinical Professor - Melanoma Oncology

150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.

Dose Level -1:

BKM120 60 mg daily Vemurafenib 480 mg bid

Phase I, Dose Level 1:

BKM120 60 mg daily Vemurafenib 720 mg bid

Phase I, Dose Level 2:

BKM120 80 mg daily Vemurafenib 720 mg bid

Phase I, Dose Level 3:

BKM120 100 mg daily Vemurafenib 720 mg bid Phase I, Dose Level 4 BKM120 100 mg daily Vemurafenib 960 mg bid Phase II 150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.

BKM120 Combined with Vemurafenib (PLX4032): Phase I is 3+3 dose escalation study to identify the recommended phase 2 dose (RP2D)

Vemurafenib-Naïve

Vemurafenib-Resistant

Total

Age, Continuous

Sex: Female, Male

Study was terminated early due to dose limiting toxicities.

Alain Algazi

Vemurafenib-Naïve and Vemurafenib-Resistant populations received:

150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.

Dose Level -1:

BKM120 60 mg daily Vemurafenib 480 mg bid

Phase I, Dose Level 1:

BKM120 60 mg daily Vemurafenib 720 mg bid

Determination of MTD

Phase 1 - Safety & Recommended Phase 2 Dose (RP2D)

150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.

Dose Level -1:

BKM120 60 mg daily Vemurafenib 480 mg bid

Phase I, Dose Level 1:

BKM120 60 mg daily Vemurafenib 720 mg bid

Phase I, Dose Level 2:

BKM120 80 mg daily Vemurafenib 720 mg bid

Phase I, Dose Level 3:

BKM120 100 mg daily Vemurafenib 720 mg bid

Phase I, Dose Level 4 BKM120 100 mg daily Vemurafenib 960 mg bid

Phase II 150 mg oral dabrafenib twice a day (bid) until disease progression, death, or unacceptable adverse events.

BKM120 Combined with Vemurafenib (PLX4032): Phase I is 3+3 dose escalation study to identify the recommended phase 2 dose (RP2D)

Data were not collected, study never advanced to Phase II.

Phase 2 - Progression-free Survival Rate

Secondary Outcome 1 Phase 2 - Objective Response Rate

Secondary Outcome 2 Phase 2 - Safety and Tolerability

Secondary Outcome 3 Phase 2 - Phosphatase and TENsin (PTEN) Expression

Data not collected: study was terminated early due to dose limiting toxicities.

Spots Global Cancer Trial Database for bkm120 combined with vemurafenib (plx4032)