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

Phase 1

Terminated

Conditions: Neoplasms

Interventions: Drug: PF-00477736
Drug: gemcitabine

Registration Number: NCT00437203

Lead Sponsor: Pfizer

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 43

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	PF-00477736	-
1	gemcitabine	-

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) of PF-00477736 When Administered in Combination With Gemcitabine	Up to Day 21 Cycle 1

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Objective Response (OR)	Baseline, Day 15 of Cycle 2 and 4 and every 4 cycles thereafter up to Week 62	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)	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
Minimum Observed Plasma Trough Concentration (Cmin)	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
Time to Reach Maximum Observed Plasma Concentration (Tmax)	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
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)]	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	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)]	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	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)	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	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Concentration of PF-00477736 in Urine	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
Plasma Decay Half-Life (t1/2)	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	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	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