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Completed

NCT Number: NCT00728468

A Study To Test The Impact Of PF- 00299804 On How The Body Handles Dextromethorphan In Cancer Patients

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.

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Key information

Conditions

Advanced Malignant Solid Tumors

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Roswell Park Cancer Institute, Buffalo, New York, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

PF-00299804

Drug

PF-00299804: Patients take oral 45 mg PF-00299804 once daily starting on Cycle 1 Day 1 until disease progression or unacceptable toxicities occur. One cycle equals 21 days. Dextromethorphan: Patient take a single 30 mg oral dose of dextromethorphan HBr three days prior to Cycle 1 Day 1, and then on Cycle 2 Day 7.

Primary outcomes

  1. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Dextromethorphan and Dextrorphan 3 Days Prior to PF-00299804 Dosing

    Time frame: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose

    Area under the plasma concentration time-curve from time zero (pre-dose) to the last measured concentration (AUClast). Dextrorphan is an active metabolite of dextromethorphan.

  2. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Dextromethorphan and Dextrorphan on Cycle 2 Day 7

    Time frame: 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

    Area under the plasma concentration time-curve from time zero (pre-dose) to the last measured concentration (AUClast). Dextrorphan is an active metabolite of dextromethorphan.

  3. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) For Dextrorphan 3 Days Prior to PF-00299804 Dosing

    Time frame: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose

    AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). Dextrorphan is an active metabolite of dextromethorphan.

  4. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) For Dextrorphan on Cycle 2 Day 7

    Time frame: 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

    AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). Dextrorphan is an active metabolite of dextromethorphan.

  5. Maximum Observed Plasma Concentration (Cmax) For Dextromethorphan and Dextrorphan 3 Days Prior to PF-00299804 Dosing

    Time frame: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose

    Dextrorphan is an active metabolite of dextromethorphan.

  6. Maximum Observed Plasma Concentration (Cmax) For Dextromethorphan and Dextrorphan on Cycle 2 Day 7

    Time frame: 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

    Dextrorphan is an active metabolite of dextromethorphan.

  7. Time to Reach Maximum Observed Plasma Concentration (Tmax) For Dextromethorphan and Dextrorphan 3 Days Prior to PF-00299804 Dosing

    Time frame: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose

    Dextrorphan is an active metabolite of dextromethorphan.

  8. Time to Reach Maximum Observed Plasma Concentration (Tmax) For Dextromethorphan and Dextrorphan on Cycle 2 Day 7

    Time frame: 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

    Dextrorphan is an active metabolite of dextromethorphan.

  9. Plasma Decay Half-Life (t1/2) For Dextrorphan 3 Days Prior to PF-00299804 Dosing

    Time frame: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Dextrorphan is an active metabolite of dextromethorphan.

  10. Plasma Decay Half-Life (t1/2) For Dextrorphan on Cycle 2 Day 7

    Time frame: 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

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Dextrorphan is an active metabolite of dextromethorphan.

  11. Oral Clearance For Dextromethorphan 3 Days Prior to PF-00299804 Dosing

    Time frame: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose

    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  12. Oral Clearance For Dextromethorphan on Cycle 2 Day 7

    Time frame: 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

    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  13. Urinary Metabolic Ratio (UMR) of Dextromethorphan to Dextrorphan 3 Days Prior to PF-00299804 Dosing

    Time frame: 8 hours after dosing on Day -3

    The UMR was calculated as the ratio of the amount of dextrmotherphan excreted in urine from time zero to 8 hours post-dose on Day -3 to the amount of dextrorphan excreted in urine from time zero to 8 hours post-dose on Day -3.

  14. Urinary Metabolic Ratio (UMR) of Dextromethorphan to Dextrorphan on Cycle 2 Day 7

    Time frame: 8 hours after dosing on Day 7

    The UMR was calculated as the ratio of the amount of dextrmotherphan excreted in urine from time zero to 8 hours post-dose on Day 7 to the amount of dextrorphan excreted in urine from time zero to 8 hours post-dose on Day 7.

Secondary outcomes

  1. Best Overall Response (BOR)

    Time frame: Baseline, end of every even-numbered cycle until disease progression up to end of treatment (up to 18 months)

    BOR: investigator assessment by Response Evaluation Criteria in Solid Tumors (RECIST), recorded from treatment start until disease progression/recurrence. Complete Response: disappearance of all lesions. Partial Response (PR): >=30% decrease in sum of longest diameters (SLDs) of target lesions (TLs) taking as reference baseline SLD. Progressive disease (PD): >=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of >=1 new lesion. Stable disease: neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start.

  2. Duration of Response (DR)

    Time frame: Baseline, end of every even-numbered cycle until disease progression up to end of treatment (up to 18 months)

    Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.

  3. Time to Tumor Progression (TTP)

    Time frame: Baseline, end of every even-numbered cycle until disease progression up to end of treatment (up to 18 months)

    Time in months from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.437. Tumor progression was determined from oncologic assessment data (where data meet the criteria for PD).

Other outcomes

  1. Ratio of Dextromethorphan Area Under the Curve to Dextrorphan Area Under the Curve 3 Days Prior to PF-00299804 Dosing

    Time frame: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose

    Dextrorphan is an active metabolite of dextromethorphan.

  2. Ratio of Dextromethorphan Area Under the Curve to Dextrorphan Area Under the Curve on Cycle 2 Day 7

    Time frame: 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

    Dextrorphan is an active metabolite of dextromethorphan.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Collaborators

  • Roswell Park Cancer Institute
  • South Texas Accelerated Research Therapeutics (START)

Registry information

Official study 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

Important dates

Study start
2008
Primary completion
2011
Study completion
2014
First posted
Aug 5, 2008
Registry last updated
Aug 2, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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