ClinicalTrials.gov
ClinicalTrials.gov Menu

A Safety Study Of A Monoclonal Antibody Against A5B1 Integrin In Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00915278
Recruitment Status : Terminated (The study was terminated on 26 February 2013. Risk-benefit assessment is no longer positive and does not support further development)
First Posted : June 8, 2009
Results First Posted : April 4, 2014
Last Update Posted : April 4, 2014
Sponsor:
Information provided by (Responsible Party):
Pfizer

June 3, 2009
June 8, 2009
February 25, 2014
April 4, 2014
April 4, 2014
September 2009
January 2013   (Final data collection date for primary outcome measure)
Number of Participants With Dose-limiting Toxicities (DLT) [ Time Frame: Baseline up to 6 weeks PF-04605412 ]
DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity,any >= Grade 3 adverse event (AE) graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 3.0 without a clear alternative explanation to study treatment relationship occurring during the first 6 weeks of treatment with PF‑04605412. DLT was used to determine maximum tolerated dose (MTD) in this study.
Maximum Tolerated Dose [ Time Frame: 1 year ]
Complete list of historical versions of study NCT00915278 on ClinicalTrials.gov Archive Site
  • Maximum Observed Serum Concentration (Cmax) [ Time Frame: 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 ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 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 ]
    Area under the serum concentration time-curve from zero to the last measured concentration (AUClast).
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] [ Time Frame: 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 ]
    AUC (0 - inf)= Area under the serum concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf).
  • Serum Decay Half-Life (t1/2) [ Time Frame: 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 ]
    Serum decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Time to Reach Maximum Observed Serum Concentration (Tmax) [ Time Frame: 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 ]
  • Systemic Clearance (CL) [ Time Frame: 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 ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body.
  • Volume of Distribution at Steady State (Vss) [ Time Frame: 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 ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
  • Number of Participants Positive for Anti-PF04605412 Antibodies [ Time Frame: Baseline up to end of treatment ]
    Serum samples were analyzed for anti-drug antibodies (ADA) or human anti-human antibodies (HAHA). This was used to evaluate immunogenicity.
  • Objective Response - Number of Participants With Objective Response [ Time Frame: 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 ]

    Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

    Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.

  • Percent Change in Transfer Constant (Ktrans) From Baseline to Cycle 1 Day 15 [ Time Frame: Screening, and Cycle 1 Day 15 ]
    Percent change in Ktrans for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from baseline to Cycle 1 day 15 aimed at defining the effect of PF-04605412 on tumor vasculature.
  • Percent Change in Initial Area Under the Curve (IAUC) [ Time Frame: Screening, and Cycle 1 Day 15 ]
    Percent change in the IAUC for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from baseline to Cycle 1 Day 15. IAUC reflects the contrast distribution volume (extravascular extracellular space) in addition to contrast delivery and transport across the vascular endothelium. An IAUC value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).
  • Number of Participants With Tissue Macrophage Infiltration [ Time Frame: Predose and postdose ]
    Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against tissue macrophages.
  • Number of Participants With Integrin Alpha 5 Beta 1 Expression [ Time Frame: Predose and postdose ]
    Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against integrin alpha 5 beta 1.
  • Number of Participants With CD68 Expression [ Time Frame: Predose and postdose ]
    Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies CD68.
  • Number of Participants With Granzyme B Expression [ Time Frame: Predose and postdose ]
    Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against Granzyme B.
  • Number of Participants With CD56 Expression [ Time Frame: Predose and postdose ]
    Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against CD56.
  • Number of Participants With CD16 Expression [ Time Frame: Predose and postdose ]
    Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against CD16.
  • Number of Participants With pFAK Expression [ Time Frame: Predose and postdose ]
    Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against pFAK.
  • Number of Participants With CD31 Expression [ Time Frame: Predose and postdose ]
    Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against CD31.
  • Number of Participants With Caspase 3 Expression [ Time Frame: Predose and postdose ]
    Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against Caspase 3.
  • Number of Participants With Ki67 Expression [ Time Frame: Predose and postdose ]
    Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against Ki67.
  • Number of Participants With Perforin Expression [ Time Frame: Predose and postdose ]
    Immunohistochemical staining of tissue biopsies was performed with monoclonal antibodies directed against Perforin.
  • Safety [ Time Frame: 1 year ]
  • Pharmacokinetics [ Time Frame: 1 year ]
  • Immunogenicity [ Time Frame: 1 year ]
  • Ktrans and related dynamic contrast-enhanced magnetic resonance imaging (DCE- MRI) parameters [ Time Frame: 1 year ]
  • Objective Response [ Time Frame: 1 year ]
Not Provided
Not Provided
 
A Safety Study Of A Monoclonal Antibody Against A5B1 Integrin In Solid Tumors
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
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.
Not Provided
Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Advanced Non-Hematologic Malignancies
Drug: PF-04605412
PF-04605412 will be administered as 2 hr IV infusion every 4 or 2 weeks. Start dose is 7.5 mg. Multiple doses are foreseen. Treatment will continue until intolerable toxicity, progression of disease or patient's refusal
Experimental: PF-04605412
Intervention: Drug: PF-04605412
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
33
60
January 2013
January 2013   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom,   United States
 
 
NCT00915278
B1001001
No
Not Provided
Not Provided
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
February 2014

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