Study Of PF-00562271, Including Patients With Pancreatic, Head And Neck, Prostatic Neoplasms

NCT00666926 | Completed Phase 1 Results

• 1 other identifier: A8031001
• Study Type: interventional
• Target: 99
• Locations: 3 countries
• Sites: 4

Brief Summary

Phase 1 safety, pharmacokinetics, and pharmacodynamics trial of the focal adhesion kinase (FAK) inhibitor PF-00562271 in patients with positive Positron Emission Tomography \[PET\] scans due to advanced non-hematologic malignancies, including pancreatic, head and neck, and prostatic neoplasms, and patients with other malignancies appropriate for serial biopsy. Screening consists of a Fluorodeoxyglucose Positron Emission Tomography \[FDG-PET\] and tumor imaging, medical history, physical examination, Eastern Cooperative Oncology Group \[ECOG\] performance status, blood draws, a pregnancy test for female patients of childbearing potential. Treatment consists of PF00562271 tablets continued until progression of disease, unacceptable toxicity, or patient request. Evaluations for bioactivity are measured by serial FDG-PET and blood tests for biomarkers related to FAK and PYK2 kinase activities.

Conditions

Head and Neck Neoplasm; Prostatic Neoplasm; Pancreatic Neoplasm

Keywords

Pancreatic Neoplasm; Head and Neck neoplasm; Prostatic neoplasms; Focal Adhesion Kinase; Phase 1; Pharmacodynamics; FDG-PET

Outcome Measures

Primary Outcomes (2)

• Number of Participants With First Cycle Dose Limiting Toxicities (DLTs)

  At least possibly attributable to study treatment (Tx): Grade (Gr) 4 neutropenia (absolute neutrophil count \[ANC\] \<500 cells/mm\^3) for \>7 days or Gr 3 febrile neutropenia (ANC \<1000/mm\^3, fever ≥38 degrees Celsius; Gr 4 thrombocytopenia (platelets \<25,000 cells/mm\^3); Gr ≥3 non-hematologic toxicity despite adequate medical intervention; Gr ≥3 confirmed prolonged QTc interval (\>500 milliseconds \[msec\]); confirmed cardiac troponin I ≥99 percentile of reference range; Tx related toxicities with failure to receive ≥18 days Tx in 21-day cycle or inability to resume current dose level ≤14 days.

  Baseline up to Cycle 1 Day 21 (C1.D21)

• Percentage of Participants With Tumor Metabolic Response (Reduction of ≥15%) in Positron Emission Tomography With F-18-fluorodeoxyglucose (FDG-PET)

  Metabolic response demonstrated in any tumor reduction of ≥15% in tumor FDG standardized uptake value (SUV) in Cycle 1; based on the recommendations of the European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Participant must have had a baseline PET with at least 1 tumor lesion demonstrating an FDG SUV of ≥5.

  Baseline, C1.D14

Secondary Outcomes (22)

• Maximum Serum Concentration (Cmax): PF-00562271 C0.D1, C1.D1

  Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 morning (am) dose

• Maximum Serum Concentration (Cmax): PF-00562271 C1.D14

  Escalation and Expansion E1 and E2 cohorts: C1.D14 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12 (if BID) or 24 (if QD) hrs post am dose

• Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C0.D1, C1.D1

  Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 am dose

• Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C1.D14

  Escalation and Expansion E1 and E2 cohorts: C1.D14 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12 (if BID) or 24 (if QD) hrs post am dose

• Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-00562271 C0.D1, C1.D1

  Escalation cohorts: C0.D1 0 hour (0 hr=pre-dose PF-00562271), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post dose; Expansion E1 US cohort: C1.D1 0 hr (prior to MDZ dose); E1 non-US and E2 cohort: C1.D1 0 hr and 0.5, 1, 2, 4 hrs post C1.D1 am dose

Study Arms (4)

1

EXPERIMENTAL

Drug: PF00562271

2

EXPERIMENTAL

Drug: PF00562271

3

EXPERIMENTAL

Drug: PF00562271

4

EXPERIMENTAL

Drug: PF00562271

Interventions

PF00562271 DRUG

125 mg twice daily \[BID\] with food, tablet

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pancreatic, head and neck, and prostatic neoplasms, and patients with non-hematologic malignancies who have tumor appropriate for serial biopsy.
• Adequate organ function, including bilirubin less than 1.5 x ULN, and \[Eastern Cooperative Oncology Group\] ECOG performance status of 0-2.

You may not qualify if:

• Clinically significant gastrointestinal abnormalities, requirement for systemic anticoagulants or potent CYP 3A4 inhibitors, and history of clinically significant cardiac or pulmonary disorders.

Sponsors & Collaborators

• Verastem, Inc.: lead

Study Sites (4)

Pfizer Investigational Site

Aurora, Colorado, 80045, United States

Location

Pfizer Investigational Site

Nashville, Tennessee, 37203, United States

Location

Pfizer Investigational Site

East Melbourne, Victoria, 3002, Australia

Location

Pfizer Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Head and Neck Neoplasms; Prostatic Neoplasms; Pancreatic Neoplasms

Interventions

PF-00562271

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Limitations and Caveats

PET and RECIST Response Analysis Sets as defined in Protocol Amendment 3 dated 20Mar2007 are reported in Basic Results per the revised definitions in Statistical Analysis Plan version 2 dated 11Apr2008.

Results Point of Contact

• Title: Mitchell Keegan
• Organization: Verastem, Inc.

mkeegan@verastem.com

617-252-9300

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2008
• First Posted: April 25, 2008
• Study Start: December 1, 2005
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: March 21, 2013
• Results First Posted: June 14, 2012

Record last verified: 2013-03

Locations

AU (1); US (2); CA (1)