Phase 1 Dose-escalation PK/PD Trial in Advanced Cancer Patients

Phase 1

Completed

• Conditions: Advanced Cancer
• Interventions: Drug: RDEA119

• Registration Number: NCT00610194
• Lead Sponsor: Bayer

Brief Summary

Primary Objective: To evaluate the safety of escalating oral doses of RDEA119, a MEK inhibitor, in advanced cancer patients.

Secondary Objectives:

* To describe the initial PK of different doses of RDEA119 when given once orally on Day 1 of the study

* To describe the PK of different doses of RDEA119 when given orally as continuous dosing.

* To examine the inhibition of MEK products (p-ERK), cytokine products, and other protein biomarkers

* To expand the MTD dose cohort to evaluate the safety, tolerability and PK/PD of the recommended Phase 2 dose

* To explore the presence of genotype, PD markers, cell growth and a marker of apoptosis, in paired tumor biopsy samples of patients' tumors pre-dose and during dosing in a minimum of 10 patients in the expanded cohort

Detailed Description

Not available

Study Timeline

• Study Start: 2007-11-28
• Study First Submitted: 2008-01-02
• Study First Submitted QC: 2008-01-24
• Study First Posted: 2008-02-07
• Primary Completion: 2010-11-24
• Study Completion: 2012-08-01
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-16
• Last Update Posted: 2023-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 69

Inclusion Criteria

• Histological or cytological confirmed solid tumor. - Advanced metastatic or locally recurrent disease for which no proven effective therapy exists. - In the expanded MTD cohort, a minimum of 10 patients must have an accessible tumor that is amendable to biopsy (cut or needle) at the start and during the study. For patients not in the biopsy group, a block from the patient's original diagnostic biopsy/excision, if available, may be used for genotype analysis. - ECOG performance status of 0-1. - Life expectancy of > or equal to 3 months. - Acceptable hematology, clinical chemistry, and coagulation laboratory values. - Patient must be acceptable for treatment and follow up according to the Investigator. - Patent must have agreed to and signed the Informed Consent. - Patient has within normal range cardiac function as measured by echocardiogram or MUGA scan.

Exclusion Criteria

• Use of investigational agents or devices within the last 28 days. - Major surgery within 30 days of start of study. - Patients with documented CNS metastasis who are not off steroids and other CNS therapies - Evidence of uncontrolled active infections. - Other serious medical or psychiatric illness. - Significant cardiac dysfunction including congestive heart failure (NYHA Class III or IV); myocardial infarction or ventricular tachyarrhythmia within the last 6 months; major conduction abnormalities unless corrected with a cardiac pacemaker; prolonged QTc >460msec. - Patients with known hypersensitivity to any of the drugs or components given in this protocol. - Pregnancy. - Women or men of childbearing potential not willing to use effective contraception, including barrier protection. - Patients with abdominal fistula, GI perforation, intra-abdominal abscess, or small bowel resection, any of which is within 6 months of study entry. - Patients with abdominal radiation resulting in chronic diarrhea. - Because RDEA119 is primarily metabolized by CYP3A4 and CYP2C19, inhibitors and inducers of these enzymes should be avoided. - Patients with known HIV infection will be excluded.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1	RDEA119	In the dose escalation phase, subjects will receive a single oral dose of RDEA119 on Day 1, wait 1 week, then begin a 28-day course of daily continuous dosing of RDEA119. In the expanded MTD phase, subjects will receive RDEA119 once or twice a day beginning on Day 1, and begin a 28-day course of continuous dosing at that time.

Primary Outcome Measures

Name	Time	Method
Safety will be assessed as adverse and drug related events, clinical laboratory test results (hematology, chemistry, coagulation, and urinalysis), vital signs, 12-lead electrocardiograms (ECGs), and physical examination	35 Days

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics and Pharmacodynamics	35 Days

Trial Locations

Locations (3)

TGen Clinical Research Services at Scottsdale Healthcare; 🇺🇸 Scottsdale, Arizona, United States

Roswell Park Cancer; 🇺🇸 Buffalo, New York, United States

UCHSC; 🇺🇸 Aurora, Colorado, United States