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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00610194
First received: January 2, 2008
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

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

Condition Intervention Phase
Advanced Cancer
Drug: RDEA119
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Center Phase 1, Dose-Escalation Trial to Determine the Safety and Pharmacokinetics/Pharmacodynamics of RDEA119, A MEK Inhibitor, in Advanced Cancer Patients

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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 [ Time Frame: 35 Days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics and Pharmacodynamics [ Time Frame: 35 Days ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: November 2007
Study Completion Date: August 2012
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
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.
Drug: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00610194

Locations
United States, Arizona
TGen Clinical Research Services at Scottsdale Healthcare
Scottsdale, Arizona, United States, 85258
United States, Colorado
UCHSC
Aurora, Colorado, United States, 80045
United States, New York
Roswell Park Cancer
Buffalo, New York, United States, 14263
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer