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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00932126




Registration number
NCT00932126
Ethics application status
Date submitted
30/06/2009
Date registered
3/07/2009
Date last updated
28/10/2015

Titles & IDs
Public title
This Is The First Study Using Escalating Doses Of PF-03758309, An Oral Compound, In Patients With Advanced Solid Tumors
Scientific title
Phase 1, Open Label, Dose-Escalation, Safety, Pharmacokinetic And Pharmacodynamic Study Of Single Agent PF-03758309, An Oral PAK4 Inhibitor, In Patients With Advanced Solid Tumors
Secondary ID [1] 0 0
B1301001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PF-03758309

Experimental: 1 -


Treatment: Drugs: PF-03758309
Oral PF-03758309 will be administered in capsules (once or twice daily) until toxicity, progressive disease, or patient refusal to continue on therapy. The starting dose is 1 mg once daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Cycle 1 Dose-limiting Toxicities (DLT)
Timepoint [1] 0 0
Baseline (up to 30 days prior to first study drug administration) till 28 days after the last treatment administration (end of Cycle 1 [28 days])
Secondary outcome [1] 0 0
Number of Participants With Objective Response
Timepoint [1] 0 0
Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 2 months until when the last participant was discontinued due to disease progression in Month 27 of the study
Secondary outcome [2] 0 0
Time to Tumor Progression (TTP)
Timepoint [2] 0 0
Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 2 months until when the last participant was discontinued due to disease progression in Month 27 of the study
Secondary outcome [3] 0 0
Duration of Response
Timepoint [3] 0 0
Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 2 months until when the last participant was discontinued due to disease progression in Month 27 of the study
Secondary outcome [4] 0 0
Maximum Observed Plasma Concentration (Cmax)
Timepoint [4] 0 0
predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, on Cycle 1 Day 8 and Cycle 2-4 Day 1 at pre-dose and 2 hours post morning dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
Secondary outcome [5] 0 0
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Timepoint [5] 0 0
predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, on Cycle 1 Day 8 and Cycle 2-4 Day 1 at pre-dose and 2 hours post morning dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
Secondary outcome [6] 0 0
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Timepoint [6] 0 0
predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, on Cycle 1 Day 8 and Cycle 2-4 Day 1 at pre-dose and 2 hours post morning dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
Secondary outcome [7] 0 0
Area Under the Concentration-Time Curve From Time 0 to 12 Hours Post Morning Dose [AUC(0-12)]
Timepoint [7] 0 0
pre-dose and 12 hours post morning dose
Secondary outcome [8] 0 0
Minimum Observed Plasma Trough Concentration (Cmin)
Timepoint [8] 0 0
predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
Secondary outcome [9] 0 0
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Timepoint [9] 0 0
predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose
Secondary outcome [10] 0 0
PAK (p21 Activated Kinase)-Related Pathway Molecule Expression Modulation by PF-03758309 in Tumor and Surrogate Tissue
Timepoint [10] 0 0
Screening, 0, 2, 4, and 72 hours post dose Cycle 2 Day 8. A 6th sample of hair follicle could be requested at 6 or 8 hours post-dose if necessary. For fresh tumor tissue, baseline and between Day 8 and 22 of Cycle 1 in participants with accessible tumors
Secondary outcome [11] 0 0
Baseline Tumor Expression of PAK-related Pathway Molecules and Other Known Biomarkers
Timepoint [11] 0 0
Baseline

Eligibility
Key inclusion criteria
* Advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available.
* ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) must be 0 or 1.
* Adequate bone marrow, liver and kidney function.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients with known brain metastases.
* Previous high dose chemotherapy requiring stem cell rescue.
* Prior irradiation to >25% of the bone marrow.
* Active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV).
* Current active treatment in another clinical study.
* Pregnancy or breast feeding.
* Active inflammatory gastrointestinal disease, chronic diarrhea (unless related to underlying malignancy or prior related treatment) or history of abdominal fistula, gastrointestinal perforation, peptic ulcer disease, or intra-abdominal abscess within 6 months prior to study enrollment.

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
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2011
Sample size
Target
Accrual to date
Final
35
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
Colorado

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

Ethics approval
Ethics application status

Summary
Brief summary
This is the first study using PF-03758309, an oral compound, in patients with advanced solid tumors. In this study different doses of PF-03758309 will be administered to different groups of patients. The study will assess the compound's safety, the blood levels of PF-03758309 during the treatment and the effect of the compound on the tumor cells.
Trial website
https://clinicaltrials.gov/study/NCT00932126
Trial related presentations / publications
Mpilla GB, Uddin MH, Al-Hallak MN, Aboukameel A, Li Y, Kim SH, Beydoun R, Dyson G, Baloglu E, Senapedis WT, Landesman Y, Wagner KU, Viola NT, El-Rayes BF, Philip PA, Mohammad RM, Azmi AS. PAK4-NAMPT Dual Inhibition Sensitizes Pancreatic Neuroendocrine Tumors to Everolimus. Mol Cancer Ther. 2021 Oct;20(10):1836-1845. doi: 10.1158/1535-7163.MCT-20-1105. Epub 2021 Jul 12.
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/study/NCT00932126