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

Advanced Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00610194
• Other study ID #: 15505
• Secondary ID: RDEA119-101
• Status: Completed
• Phase: Phase 1
• Start date: November 28, 2007
• Est. completion date: August 1, 2012

Study information

• Verified date: October 2023
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: August 1, 2012
• Est. primary completion date: November 24, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Cancer
• Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	UCHSC	Aurora	Colorado
United States	Roswell Park Cancer	Buffalo	New York
United States	TGen Clinical Research Services at Scottsdale Healthcare	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

United States, 

References & Publications (1)

Weekes CD, Von Hoff DD, Adjei AA, Leffingwell DP, Eckhardt SG, Gore L, Lewis KD, Weiss GJ, Ramanathan RK, Dy GK, Ma WW, Sheedy B, Iverson C, Miner JN, Shen Z, Yeh LT, Dubowy RL, Jeffers M, Rajagopalan P, Clendeninn NJ. Multicenter phase I trial of the mit — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Pharmacokinetics and Pharmacodynamics		35 Days