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This Is The First Study Using Escalating Doses Of PF-03758309, An Oral Compound, In Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT00932126
Recruitment Status : Terminated (See termination reason in detailed description.)
First Posted : July 3, 2009
Results First Posted : March 6, 2013
Last Update Posted : October 28, 2015
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE June 30, 2009
First Posted Date  ICMJE July 3, 2009
Results First Submitted Date  ICMJE December 11, 2012
Results First Posted Date  ICMJE March 6, 2013
Last Update Posted Date October 28, 2015
Study Start Date  ICMJE September 2009
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 30, 2013)
Number of Participants With Cycle 1 Dose-limiting Toxicities (DLT) [ Time Frame: 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]) ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: July 2, 2009)
Maximum tolerated dose for two different schedules consecutively explored: continuous and intermittent. [ Time Frame: 10 Months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2013)
  • Number of Participants With Objective Response [ Time Frame: 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 ]
    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.
  • Time to Tumor Progression (TTP) [ Time Frame: 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 ]
    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])
  • Duration of Response [ Time Frame: 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 ]
    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.
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 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 ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 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 ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 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 ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
  • Area Under the Concentration-Time Curve From Time 0 to 12 Hours Post Morning Dose [AUC(0-12)] [ Time Frame: pre-dose and 12 hours post morning dose ]
  • Minimum Observed Plasma Trough Concentration (Cmin) [ Time Frame: 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 ]
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) [ Time Frame: 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 ]
  • PAK (p21 Activated Kinase)-Related Pathway Molecule Expression Modulation by PF-03758309 in Tumor and Surrogate Tissue [ Time Frame: 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 ]
  • Baseline Tumor Expression of PAK-related Pathway Molecules and Other Known Biomarkers [ Time Frame: Baseline ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2009)
  • To evaluate the safety profile of PF-03758309 [ Time Frame: 22 Months ]
  • Pharmacokinetic study [ Time Frame: 22 Months ]
  • Pharmacodynamic study [ Time Frame: 22 Months ]
  • Effect of PF-03758309 on functional imaging with FLT-PET (Positron Emission Tomography) [ Time Frame: 22 Months ]
  • Antitumor activity of PF-03758309 [ Time Frame: 22 Months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE This Is The First Study Using Escalating Doses Of PF-03758309, An Oral Compound, In Patients With Advanced Solid Tumors
Official Title  ICMJE 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
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.
Detailed Description The study was prematurely terminated on 26Jul2011 due to the undesirable PK characteristics of PF-03758309 and the lack of an observed dose-response relationship. There were no safety concerns that contributed to the study termination.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE Drug: 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.
Study Arms  ICMJE Experimental: 1
Intervention: Drug: PF-03758309
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 24, 2012)
35
Original Estimated Enrollment  ICMJE
 (submitted: July 2, 2009)
50
Actual Study Completion Date  ICMJE December 2011
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00932126
Other Study ID Numbers  ICMJE B1301001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP