NCT02022982

PALBOCICLIB + PD-0325901 for NSCLC & Solid Tumors

Phase I Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the MEK Inhibitor PD-0325901 for Patients With KRAS Mutant Non-Small Cell Lung Cancer and Other Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (actual)
• Sponsor: Dana-Farber Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This research study is evaluating the experimental drug palbociclib in combination with another experimental drug PD-0325901 as a possible treatment for cancers with KRAS mutations, particularly for those which started in the lung.

Detailed description

This will be an open label Phase I dose escalation study evaluating the combination of the CDK4/6 inhibitor palbociclib (PD-0332991) and the MEK inhibitor PD-0325901. To determine the maximally tolerated dose (MTD) and recommended phase 2 dose (RP2D), a 3+3 dose escalation protocol will be undertaken. Once the RP2D has been determined, the study will then evaluate, in a randomized phase II study design, the combination of palbociclib and PD-0325901 compared to PD-0325901 alone and palbociclib alone in KRAS mutant NSCLC. * Phase 1: The investigators are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have cancer, not everyone who participates in this research study will receive the same dose of the study drug. The dose the participant receives will depend on the number of participants who have been enrolled in the study before and how well the dose has been tolerated. * Study Drug(s): The participant will be given a study drug-dosing calendar for each treatment cycle. Each treatment cycle lasts 4 weeks during which time you will be taking the study drug for 3 weeks at a time. The participant will take Palbociclib by mouth once a day, every day for 3 weeks. The participant will take PD-0325901 by mouth twice a day, every day for 3 weeks. * Clinical Exams: During all cycles the participant will have a physical exam and will be asked questions about general health and specific questions about any problems that they might be having and any medications they may be taking. * Scans (or Imaging tests): The investigators will assess the participant's tumor by either a CT scan or MRI * Blood Tests: These are special tests to check the amount of drug and the amount of tumor DNA in the participant's blood at specific points in time. Secondary Outcomes: * Evaluate PK parameters for the combination of palbociclib and PD-0325901 * Confirm target engagement of palbociclib and PD-0325901 in patients undergoing pre- and on-treatment biopsies in an expansion cohort at the MTD * Evaluate preliminary clinical efficacy of the combination of palbociclib and PD-0325901 in patients with tumors harboring KRAS mutations.

Conditions

• KRAS Mutant Non-Small Cell Lung Cancer
• Solid Tumors

Interventions

Type	Name	Description
DRUG	Palbociclib	Palbociclib will be administered orally once daily, 3 weeks out of every 4 in each cycle. The initial dose for phase 1 of the study will be 75 mg daily. Dosing will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. No pre-medications for palbociclib are required. It should be administered without food with patients fasting for 1 hour prior and 2 hours post drug administration.
DRUG	PD-0325901	PD-0325901 will be administered orally twice daily, 3 weeks out of every 4 in each cycle. The initial dose for phase 1 of the study will be 2 mg twice daily. Dosing will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. PD-0325901 will be administered using a flat-dosing plan. No premedications are required. As the effect of food on PD-0325901 is uncertain, patients will be permitted to dose either fasting or after food.

Timeline

• Start date: 2014-01-01
• Primary completion: 2017-11-01
• Completion: 2021-06-30
• First posted: 2013-12-30
• Last updated: 2024-03-19

Locations

1 site across 1 country: United States