Clinical trial NCT00437203: PF-00477736 Is Being Studied In Advanced Solid Tumors In Combination With Chemotherapy With Gemcitabine
Official title: Phase I Study of PF-00477736 With Gemcitabine In Patients With Advanced Solid Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Advanced cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-02-19
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of PF-00477736 When Administered in Combination With Gemcitabine
timeFrame: Up to Day 21 Cycle 1
Secondary outcomes:
measure: Number of Participants With Objective Response (OR)
timeFrame: Baseline, Day 15 of Cycle 2 and 4 and every 4 cycles thereafter up to Week 62
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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
measure: Minimum Observed Plasma Trough Concentration (Cmin)
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 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
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)]
timeFrame: 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
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-48)]
timeFrame: 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
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: 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
measure: Concentration of PF-00477736 in Urine
timeFrame: 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
measure: Plasma Decay Half-Life (t1/2)
timeFrame: 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
measure: Metabolite Profile of PF-00477736 in Plasma and Urine
timeFrame: 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
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Pfizer Investigational Site
state: California
city: Los Angeles
country: United States
facility: Pfizer Investigational Site
state: California
city: Santa Monica
country: United States
facility: Pfizer Investigational Site
state: California
city: Santa Monica
country: United States
facility: Pfizer Investigational Site
state: California
city: New York
country: United States
facility: Pfizer Investigational Site
state: New York
city: New York
country: United States
facility: Pfizer Investigational Site
state: New York
city: East Melbourne
country: Australia
facility: Pfizer Investigational Site
state: Victoria
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: