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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00437203




Registration number
NCT00437203
Ethics application status
Date submitted
16/02/2007
Date registered
19/02/2007
Date last updated
3/04/2012

Titles & IDs
Public title
PF-00477736 Is Being Studied In Advanced Solid Tumors In Combination With Chemotherapy With Gemcitabine
Scientific title
Phase I Study of PF-00477736 With Gemcitabine In Patients With Advanced Solid Malignancies
Secondary ID [1] 0 0
A8211001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PF-00477736
Treatment: Drugs - gemcitabine

Experimental: 1 -


Treatment: Drugs: 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.

Treatment: Drugs: 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).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose (MTD) of PF-00477736 When Administered in Combination With Gemcitabine
Timepoint [1] 0 0
Up to Day 21 Cycle 1
Secondary outcome [1] 0 0
Number of Participants With Objective Response (OR)
Timepoint [1] 0 0
Baseline, Day 15 of Cycle 2 and 4 and every 4 cycles thereafter up to Week 62
Secondary outcome [2] 0 0
Maximum Observed Plasma Concentration (Cmax)
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Minimum Observed Plasma Trough Concentration (Cmin)
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)]
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-48)]
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
Concentration of PF-00477736 in Urine
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
Plasma Decay Half-Life (t1/2)
Timepoint [9] 0 0
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
Secondary outcome [10] 0 0
Metabolite Profile of PF-00477736 in Plasma and Urine
Timepoint [10] 0 0
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

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2011
Sample size
Target
Accrual to date
Final
43
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Pfizer Investigational Site - East Melbourne
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
New York

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00437203
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00437203