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PF-00477736 Is Being Studied In Advanced Solid Tumors In Combination With Chemotherapy With Gemcitabine

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00437203
First received: February 16, 2007
Last updated: March 6, 2012
Last verified: March 2012
History of Changes
  Purpose

To determine the overall safety of PF-00477736 when given in combination with gemcitabine, a chemotherapy agent, in patients with advanced solid tumors and determine the maximum dose of PF-00477736 that can be safely given in combination with gemcitabine. This is the first study of PF-00477736 in humans.


Condition Intervention Phase
Neoplasms
 Drug: PF-00477736
Drug: gemcitabine
 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of PF-00477736 With Gemcitabine In Patients With Advanced Solid Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of PF-00477736 When Administered in Combination With Gemcitabine [ Time Frame: Up to Day 21 Cycle 1 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of Participants With Objective Response (OR) [ Time Frame: Baseline, Day 15 of Cycle 2 and 4 and every 4 cycles thereafter up to Week 62 ] [ Designated as safety issue: No ]
    OR based assessment of confirmed complete response(CR)/confirmed partial response(PR)/stable disease(SD)/progressive disease(PD) as per Response Evaluation Criteria in Solid Tumors(RECIST).CR:disappearance of target lesions;PR:at least(>=) 30% decrease in sum of longest dimensions of target lesions(reference:baseline sum of longest dimensions);PD:>=20% increase in sum of longest dimensions of target lesions(reference:smallest sum of longest dimensions recorded since treatment started)/appearance of any new lesions;SD:no adequate shrinkage to qualify for PR/adequate increase to qualify for PD.

  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 ] [ Designated as safety issue: No ]
  • Minimum Observed Plasma Trough Concentration (Cmin) [ Time Frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] [ Time Frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start: Day 1, 8 Cycle 0 ] [ Designated as safety issue: No ]
    AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-48)] [ Time Frame: 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 ] [ Designated as safety issue: No ]
    AUC (0-48)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-48).

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).

  • Concentration of PF-00477736 in Urine [ Time Frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life (t1/2) [ Time Frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Metabolite Profile of PF-00477736 in Plasma and Urine [ Time Frame: 0(pre-dose), 0.25, 1, 3, 3.25, 3.5, 4, 6, 8, 10, 24 hr post-infusion start:Day 1, 8 Cycle 0 Cohort 1-3; 0(pre-dose), 0.25, 1, 2, 24, 24.25, 24.5, 25, 27, 29, 31, 48 hr post-infusion start:Day 1-2, 8-9 Cycle 0 Cohort 4-8; Day 2-3, 9-10 Cycle 1 Cohort 9-10 ] [ Designated as safety issue: No ]

Enrollment: 43
Study Start Date: December 2006
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: PF-00477736
  • Escalating doses of PF-00477736 will be administered intravenously on Days 2 and 9 and gemcitabine will be administered intravenously on Days 1 and 8 of a 21-day cycle (doses to be evaluated range from 750 to 1250 mg/m2 in three separated cohorts).
  • If a patient is administered Cycle 0 - only PF-0047736 will be administered intravenously on Days 1 and 8 of a 21-day cycle for patients who have a 3-hour infusion and Days 1 and 8 of a 14-day cycle for patients who have a 24-hour infusion.
Drug: gemcitabine
gemcitabine will be administered intravenously on Days 1 and 8 of a 21-day cycle (doses to be evaluated range from 750 to 1250 mg/m2 in three separated cohorts).

Detailed Description:

The study was closed to enrollment as of 17 May 2010 due to business reasons. The patient on study continued treatment until 19 April 2011 when stopped for complete response. Premature closure was not prompted by any safety or efficacy concerns.

  Eligibility

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

Inclusion Criteria:

  • Histological or cytopathological diagnosis of solid malignancy that is refractory to standard therapy or for which no curative therapy exists.
  • ECOG performance status 0 or 1.
  • Adequate blood cell counts, kidney function and liver function.

Exclusion Criteria:

  • Prior treatment with gemcitabine.
  • Uncontrolled brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease.
  • NCI CTC Grade 2 or higher ARDS, non-infectious pneumonitis, or pulmonary fibrosis.
  • NCI CTC Grade 2 or higher cardiovascular toxicities with the exception of NCI CTC Grade 3 hypertension that is well controlled.
  • Known human immunodeficiency virus (HIV) seropositivity.
  • Concurrent treatment with anticoagulants or known coagulopathy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00437203

Locations
United States, California
Pfizer Investigational Site
Los Angeles, California, United States, 90095
Pfizer Investigational Site
Los Angeles, California, United States, 90095-6984
Pfizer Investigational Site
Santa Monica, California, United States, 90404
Pfizer Investigational Site
Santa Monica, California, United States, 90403
United States, New York
Pfizer Investigational Site
New York, New York, United States, 10022
Pfizer Investigational Site
New York, New York, United States, 10065
Australia, Victoria
Pfizer Investigational Site
East Melbourne, Victoria, Australia, 3002
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
To obtain contact information for a study center near you, click here.  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00437203     History of Changes
Other Study ID Numbers: A8211001
Study First Received: February 16, 2007
Results First Received: March 6, 2012
Last Updated: March 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Advanced cancer

Additional relevant MeSH terms:
Neoplasms
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
 Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on June 18, 2013