Clinical trial NCT00666926: Study Of PF-00562271, Including Patients With Pancreatic, Head And Neck, Prostatic Neoplasms
Official title: A Phase 1, Open-Label, Dose Escalation Study To Evaluate Safety, Pharmacokinetics And Pharmacodynamics Of PF-00562271 In Patients With Advanced Non-Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Verastem, Inc.
Sponsor class: INDUSTRY
First posted: 2008-04-25
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

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

Primary outcomes:
measure: Number of Participants With First Cycle Dose Limiting Toxicities (DLTs)
timeFrame: Baseline up to Cycle 1 Day 21 (C1.D21)
measure: Percentage of Participants With Tumor Metabolic Response (Reduction of ≥15%) in Positron Emission Tomography With F-18-fluorodeoxyglucose (FDG-PET)
timeFrame: Baseline, C1.D14
Secondary outcomes:
measure: Maximum Serum Concentration (Cmax): PF-00562271 C0.D1, C1.D1
timeFrame: 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
measure: Maximum Serum Concentration (Cmax): PF-00562271 C1.D14
timeFrame: 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
measure: Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C0.D1, C1.D1
timeFrame: 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
measure: Time to Reach Maximum Observed Serum Concentration (Tmax): PF-00562271 C1.D14
timeFrame: 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
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-00562271 C0.D1, C1.D1
timeFrame: 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
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf): PF-00562271 C0.D1, C1.D1
timeFrame: 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
measure: Serum Decay Half-life (t 1/2): PF-00562271 C0.D1, C1.D1
timeFrame: 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
measure: Apparent Oral Clearance (CL/F): PF-00562271 C0. D1, C1.D1
timeFrame: 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
measure: Minimum Observed Serum Trough Concentration (Cmin): PF-00562271 C1.D14
timeFrame: 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
measure: Area Under the Curve From Time Zero to the End of the Dosing Interval (AUCtau): PF-00562271 C1.D14
timeFrame: 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
measure: Observed Accumulation Ratio (Rac): PF-00562271 C1.D14
timeFrame: Escalation (Esc) cohort: C0.D1: 0 hr, and 0.5, 1, 2, 4, 6, 7,12 hrs post dose; Expansion (Exp) cohort: C0:D1: 0 hr, and 1, 2, 4, 8 hrs post dose; Esc and Exp cohorts: C1.D14 0 hour, and 0.5, 1, 2, 4, 6, 8, 12 (if BID) or 24 (if QD) hrs post am dose
measure: Maximum Serum Concentration (Cmax): MDZ
timeFrame: C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): MDZ
timeFrame: C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf): MDZ
timeFrame: C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose
measure: Time to Reach Maximum Observed Serum Concentration (Tmax): MDZ
timeFrame: C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose
measure: Serum Decay Half-life (t 1/2): MDZ
timeFrame: C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose
measure: Apparent Oral Clearance (CL/F): MDZ
timeFrame: C0.D1, C1.D21 Expansion cohort E1 US sites only: 0 hr (prior to MDZ dosing) and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hrs post MDZ dose
measure: Percentage of Participants With Best Overall Response as Measured Using the Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Baseline up to 12 cycles (cycle=21days)
measure: Phosphorylated Focal Adhesion Kinase (pFAK)
timeFrame: Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days)
measure: Phosphorylated Mitogen Activated Pathway Kinase (pMAPK)
timeFrame: Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days)
measure: Phospho-SRC (pSRC)
timeFrame: Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days)
measure: Caspase-3
timeFrame: Baseline (up to 28 days prior to first dose) up to 12 cycles (cycle=21days)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Nashville
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: East Melbourne
country: Australia
facility: Pfizer Investigational Site
state: Victoria
city: Toronto
country: Canada
facility: Pfizer Investigational Site
state: Ontario
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: