Clinical trial NCT00728468: A Study To Test The Impact Of PF- 00299804 On How The Body Handles Dextromethorphan In Cancer Patients
Official title: A Phase 1 Open Label, Single Arm Trial To Evaluate The Effect Of Pf-00299804 On The Pharmacokinetics Of Dextromethorphan In Patients With Advanced Malignant Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Malignant Solid Tumors
Keywords: Phase 1
PF-00299804
Dextromethorphan
CYP2D6 Inhibition
Cancer Patients
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Roswell Park Cancer Institute
name: South Texas Accelerated Research Therapeutics (START)
First posted: 2008-08-05
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no

Brief summary: Research in test tubes suggests that may affect cytochrome P450 2D6 (CYP2D6), an important enzyme that is responsible for eliminating many drugs that cancer patients need to take, including dextromethorphan. The purpose of this study is to test the impact of PF-00299804 on the activity of CYP2D6, and how the human body handles dextromethorphan.

Detailed description: To assess the effect of repeated dosing with 45 mg QD PF-00299804 on the pharmacokinetics of dextromethorphan, a CYP2D6 probe, in cancer patients with advanced malignant solid tumors.

Eligibility criteria: Inclusion Criteria:

* Patients with a histologically or cytologically confirmed advanced malignant solid tumor for which there is no currently approved treatment or which is unresponsive to currently approved therapies;
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Patients with performance status 2 could be eligible upon agreement between sponsors and investigators;
* Adequate bone marrow, renal, liver and cardiac functions;

Exclusion Criteria:

* History of Interstitial Lung Disease (ILD).
* Drugs with known CYP2D6 inhibitory effects
* Drugs that are highly dependent on CYP2D6 for metabolism.
* Women who are pregnant or breastfeeding.

Primary outcomes:
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Dextromethorphan and Dextrorphan 3 Days Prior to PF-00299804 Dosing
timeFrame: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Dextromethorphan and Dextrorphan on Cycle 2 Day 7
timeFrame: Cycle 2 Day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) For Dextrorphan 3 Days Prior to PF-00299804 Dosing
timeFrame: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) For Dextrorphan on Cycle 2 Day 7
timeFrame: Cycle 2 Day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax) For Dextromethorphan and Dextrorphan 3 Days Prior to PF-00299804 Dosing
timeFrame: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax) For Dextromethorphan and Dextrorphan on Cycle 2 Day 7
timeFrame: Cycle 2 Day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) For Dextromethorphan and Dextrorphan 3 Days Prior to PF-00299804 Dosing
timeFrame: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) For Dextromethorphan and Dextrorphan on Cycle 2 Day 7
timeFrame: Cycle 2 Day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Plasma Decay Half-Life (t1/2) For Dextrorphan 3 Days Prior to PF-00299804 Dosing
timeFrame: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Plasma Decay Half-Life (t1/2) For Dextrorphan on Cycle 2 Day 7
timeFrame: Cycle 2 Day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Oral Clearance For Dextromethorphan 3 Days Prior to PF-00299804 Dosing
timeFrame: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Oral Clearance For Dextromethorphan on Cycle 2 Day 7
timeFrame: Cycle 2 Day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Urinary Metabolic Ratio (UMR) of Dextromethorphan to Dextrorphan 3 Days Prior to PF-00299804 Dosing
timeFrame: 8 hours after dosing on Day -3
measure: Urinary Metabolic Ratio (UMR) of Dextromethorphan to Dextrorphan on Cycle 2 Day 7
timeFrame: 8 hours after dosing on Day 7
Secondary outcomes:
measure: Best Overall Response (BOR)
timeFrame: Baseline, end of every even-numbered cycle until disease progression up to end of treatment (up to 18 months)
measure: Duration of Response (DR)
timeFrame: Baseline, end of every even-numbered cycle until disease progression up to end of treatment (up to 18 months)
measure: Time to Tumor Progression (TTP)
timeFrame: Baseline, end of every even-numbered cycle until disease progression up to end of treatment (up to 18 months)
Other outcomes:
measure: Ratio of Dextromethorphan Area Under the Curve to Dextrorphan Area Under the Curve 3 Days Prior to PF-00299804 Dosing
timeFrame: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Ratio of Dextromethorphan Area Under the Curve to Dextrorphan Area Under the Curve on Cycle 2 Day 7
timeFrame: Cycle 2 Day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: