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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT00932126
Ethics application status
Date submitted
30/06/2009
Date registered
2/07/2009
Date last updated
6/10/2015

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
Advanced Solid Tumors 0 0
Condition category
Condition code

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

Experimental: 1 -

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.

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) - DLT includes: Grade (GR) 4 neutropenia (NP) that persisted for >7 consecutive days; Febrile NP; GR3 NP infection; GR4 thrombocytopenia (TP); GR3 TP with bleeding; Any other GR>=3 toxicity not classified under Common Terminology Criteria for Adverse Events (CTCAE) blood or bone marrow (exception of nausea, vomiting, or diarrhea in subjects who received optimal treatment with antiemetics or anti-diarrheals); Failure to recover to an adequate condition to recommence study treatment after a 2-week delay; Failure to receive >= 80% of planned PF-03758309 dose due to study drug related toxicity
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])
Primary outcome [2] 0 0
Number of Participants With Cycle 1 Dose-limiting Toxicities (DLT) - DLT includes: Grade (GR) 4 neutropenia (NP) that persisted for >7 consecutive days; Febrile NP; GR3 NP infection; GR4 thrombocytopenia (TP); GR3 TP with bleeding; Any other GR>=3 toxicity not classified under Common Terminology Criteria for Adverse Events (CTCAE) blood or bone marrow (exception of nausea, vomiting, or diarrhea in subjects who received optimal treatment with antiemetics or anti-diarrheals); Failure to recover to an adequate condition to recommence study treatment after a 2-week delay; Failure to receive >= 80% of planned PF-03758309 dose due to study drug related toxicity
Timepoint [2] 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 - Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as =30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study =4 weeks after initial documentation of 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) - Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD])
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 - Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor 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) - Area under the plasma concentration time-curve from zero to the last measured 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
Secondary outcome [12] 0 0
Number of Participants With Objective Response - Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as =30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study =4 weeks after initial documentation of response.
Timepoint [12] 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 [13] 0 0
Time to Tumor Progression (TTP) - Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD])
Timepoint [13] 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 [14] 0 0
Duration of Response - Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Timepoint [14] 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 [15] 0 0
Maximum Observed Plasma Concentration (Cmax)
Timepoint [15] 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 [16] 0 0
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Timepoint [16] 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 [17] 0 0
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) - Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Timepoint [17] 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 [18] 0 0
Area Under the Concentration-Time Curve From Time 0 to 12 Hours Post Morning Dose [AUC(0-12)]
Timepoint [18] 0 0
pre-dose and 12 hours post morning dose
Secondary outcome [19] 0 0
Minimum Observed Plasma Trough Concentration (Cmin)
Timepoint [19] 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 [20] 0 0
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Timepoint [20] 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 [21] 0 0
PAK (p21 Activated Kinase)-Related Pathway Molecule Expression Modulation by PF-03758309 in Tumor and Surrogate Tissue
Timepoint [21] 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 [22] 0 0
Baseline Tumor Expression of PAK-related Pathway Molecules and Other Known Biomarkers
Timepoint [22] 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
Gender
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
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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/show/NCT00932126
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/show/NCT00932126