NCT01841463

Study of an Oral Cdk Inhibitor Administered With an Oral BRAF Inhibitor in Patients With Advanced or Inoperable Malignant Melanoma With BRAF Mutation

An Open Label, Multicenter, Phase I Extension Study of an Oral Cdk Inhibitor P1446A-05 Administered With an Oral BRAF Inhibitor Vemurafenib (Zelboraf®) in Patients With Advanced or Inoperable Malignant Melanoma With BRAF Mutation

• Status: Suspended
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: Piramal Enterprises Limited · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

* An Open Label, Multicenter, Phase I Extension Study of an Oral Cdk Inhibitor P1446A-05 Administered with an Oral BRAF Inhibitor Vemurafenib (Zelboraf®) in Patients with Advanced or Inoperable Malignant Melanoma with BRAF Mutation * The primary objective is to determine the safety, maximum tolerated dose (MTD), and dose limiting toxicity (DLT) of the co-administration of P1446A-05 with vemurafenib, in melanoma patients with BRAF mutation

Conditions

• Advanced or Inoperable Malignant Melanoma With BRAF Mutation

Interventions

Type	Name	Description
DRUG	P1446A-05	\- In the 'Dose escalation' phase patients will be co-administered P1446A-05 (150, 250, 350 mg qd) \& vemurafenib (720, 960 mg bid) in a cohort of 3 to 6 patients on a 28-day cycle, until the occurrence of disease progression or unacceptable toxicity. The next higher dose during the dose escalation phase will depend upon demonstrated safety in the previous dose group. The max tolerated dose (MTD) of P1446A-05 \& vemurafenib co-administered will be determined. In the 'Extension' phase, 60 patients with BRAF V600E/K mutations (40 patients naïve to selective BRAF inhibitor therapy, \& 20 progressing on selective BRAF inhibitor therapy) will be treated at the MTD on a 28-day cycle, until the occurrence of disease progression or unacceptable toxicity to determine efficacy of the co-administration. Additionally, there will be a cohort of 10 patients who consent for mandatory serial tumor biopsy samples \& undergo 'Monotherapy' for 14 days with P1446A-05 at the MTD of the co-administration.
DRUG	Vemurafenib (Zelboraf®)	* In the 'Dose escalation' phase patients will be co-administered P1446A-05 (150, 250, 350 mg qd) and vemurafenib (720, 960 mg bid) in a cohort of 3 to 6 patients on a 28-day cycle, until the occurrence of disease progression or unacceptable toxicity. Escalation to the next higher dose during the dose escalation phase will depend upon demonstrated safety in the previous dose group. The maximum tolerated dose (MTD) of P1446A-05 and vemurafenib co-administered will be determined. * In the 'Extension' phase, 60 patients with BRAF V600E/K mutations (40 patients naïve to selective BRAF inhibitor therapy, and 20 progressing on selective BRAF inhibitor therapy) will be treated at the MTD on a 28-day cycle * Additionally, there will be a cohort of 10 patients who consent for mandatory serial tumor biopsy samples and undergo 'Monotherapy' for 14 days with P1446A-05 at the MTD of the co-administration.

Timeline

• Start date: 2013-08-01
• Primary completion: 2015-03-01
• Completion: 2016-03-01
• First posted: 2013-04-26
• Last updated: 2014-09-04

Locations

4 sites across 1 country: United States