Clinical trial NCT00915278: A Safety Study Of A Monoclonal Antibody Against A5B1 Integrin In Solid Tumors
Official title: A Phase 1 Safety, Pharmacokinetic And Pharmacodynamic Study Of The Anti-A5B1 Integrin Monoclonal Antibody PF-04605412 Administered Intravenously To Adult Patients With Advanced Or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Non-Hematologic Malignancies
Keywords: Neoplasms
monoclonal antibody
PF-04605412
advanced metastatic solid tumors
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-06-08
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Dose finding study of the MoaB PF-04605412 directed against the alpha5beta1 integrin. Main objective is to define the MTD (maximum tolerated dose) or MAD (maximum administrable dose) in cancer patients pre treated or unresponsive to standard therapies.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed advanced measurable or evaluable solid tumors unresponsive to currently available therapies, or for which there is no curative therapy
* Eastern Cooperative Oncology Group (ECOG) performance status 0 and 1
* Life expectancy more than12 weeks
* Adequate bone marrow, liver and renal function

Exclusion Criteria:

* Known brain metastasis
* Chemotherapy, radiotherapy, or any investigational cancer therapy within 4 weeks of start of screening procedures
* Major surgical procedure within 4 weeks of start of screening procedures
* Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis or melena in the past 6 months

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLT)
timeFrame: Baseline up to 6 weeks PF-04605412
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax)
timeFrame: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)]
timeFrame: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
measure: Serum Decay Half-Life (t1/2)
timeFrame: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
measure: Time to Reach Maximum Observed Serum Concentration (Tmax)
timeFrame: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
measure: Systemic Clearance (CL)
timeFrame: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
measure: Volume of Distribution at Steady State (Vss)
timeFrame: Predose, 1, 2, 2.5, 3, 6, 10, 24 hours after the start of infusion on Day 1; Days 3, 5, 8, 11, 15, 22 of Cycle 1
measure: Number of Participants Positive for Anti-PF04605412 Antibodies
timeFrame: Baseline up to end of treatment
measure: Objective Response - Number of Participants With Objective Response
timeFrame: Baseline up to 6 weeks after the first infusion of PF-04605412 (end of Cycle 2) and approximately every 6 weeks thereafter only in the absence of progressive disease
measure: Percent Change in Transfer Constant (Ktrans) From Baseline to Cycle 1 Day 15
timeFrame: Screening, and Cycle 1 Day 15
measure: Percent Change in Initial Area Under the Curve (IAUC)
timeFrame: Screening, and Cycle 1 Day 15
measure: Number of Participants With Tissue Macrophage Infiltration
timeFrame: Predose and postdose
measure: Number of Participants With Integrin Alpha 5 Beta 1 Expression
timeFrame: Predose and postdose
measure: Number of Participants With CD68 Expression
timeFrame: Predose and postdose
measure: Number of Participants With Granzyme B Expression
timeFrame: Predose and postdose
measure: Number of Participants With CD56 Expression
timeFrame: Predose and postdose
measure: Number of Participants With CD16 Expression
timeFrame: Predose and postdose
measure: Number of Participants With pFAK Expression
timeFrame: Predose and postdose
measure: Number of Participants With CD31 Expression
timeFrame: Predose and postdose
measure: Number of Participants With Caspase 3 Expression
timeFrame: Predose and postdose
measure: Number of Participants With Ki67 Expression
timeFrame: Predose and postdose
measure: Number of Participants With Perforin Expression
timeFrame: Predose and postdose
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Nashville
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Tooting
country: United Kingdom
facility: Pfizer Investigational Site
state: London
city: North Cheam
country: United Kingdom
facility: Pfizer Investigational Site
state: Surrey
city: Sutton
country: United Kingdom
facility: Pfizer Investigational Site
state: Surrey
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: