Study Of CP-751,871 In Combination With Sunitinib In Patients With Advanced Solid Tumors

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00729833
First received: July 30, 2008
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

The study is being conducted to determine the maximum tolerated dose, overall safety and tolerability profile, and pharmacokinetic profile of CP-751,871 and sunitinib when given in combination with advanced solid tumors.


Condition Intervention Phase
Advanced Cancer
Advanced Solid Tumors
Drug: CP-751,871
Drug: Sunitinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1, Open Label, Sequential Cohort, Dose Escalation Study Of CP-751,871 In Combination With Sunitinib In Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With Dose-Limiting Toxicities (DLT) [ Time Frame: Baseline up to the end of Cycle 1 (each cycle=3 weeks) ] [ Designated as safety issue: Yes ]

    Number of participants with treatment-related Grade 3/4 toxicities that occurred during the defined time frame or that resulted in greater than or equal to (>=) 7 days delay in administration of Cycle 2.

    Toxicities were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.



Secondary Outcome Measures:
  • Percentage of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for Adverse Events Grade Version 3.0 [ Time Frame: Baseline, Day 1 of every cycle, Days 8 and 15 of Cycle 1, up to end of treatment (28 days post last dose) ] [ Designated as safety issue: Yes ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. If the same participant in a given treatment had more than one occurrence in the same preferred term event category, only the worst CTCAE grade was reported. Severity grades were 0 (no change from normal or reference range), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), and 5 (death).

  • Percentage of Participants With Hematologic Laboratory Test Abnormality [ Time Frame: Baseline, Day 1 of every cycle, Days 8 and 15 of Cycle 1, up to end of treatment (28 days post last dose) ] [ Designated as safety issue: Yes ]
    Percentage of participants with hematologic laboratory abnormalities of CTC severity grades 1, 2, 3, or 4 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening or disabling).

  • Percentage of Participants With Blood Chemistry Laboratory Test Abnormality [ Time Frame: Baseline, Day 1 of every cycle, Days 8 and 15 of Cycle 1, up to end of treatment (28 days post last dose) ] [ Designated as safety issue: Yes ]
    Percentage of participants with blood chemistry laboratory abnormalities of CTC severity grades 1, 2, 3, or 4 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening or disabling).

  • Plasma Concentration at the End of Infusion (Cendinf) of Figitumumab [ Time Frame: 0.5 hour predose and 1 hour post-infusion on Day 1 of Cycles 1 and 4 ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Figitumumab [ Time Frame: 0.5 hour predose and 1 hour post-infusion on Days 1, 2, 4, 8, 15, and 22 of Cycles 1 and 4 ] [ Designated as safety issue: No ]
    AUClast is the area under the plasma concentration time-curve from zero to the last measured concentration.

  • Area Under the Curve From Time Zero to Day 22 [AUC504] of Figitumumab [ Time Frame: 0.5 hour predose and 504 hours (Day 22) post-infusion of Cycles 1 and 4 ] [ Designated as safety issue: No ]
    AUC504 is the area under the plasma concentration versus time curve from time zero (predose) to Day 22, where Day 22 is the nominal time (504 hours) of the predose sample for the next cycle.

  • Plasma Decay Half-Life (t1/2) of Figitumumab [ Time Frame: 0.5 hour predose and 1 hour post-infusion on Days 1, 2, 4, 8, and 15 of Cycles 1 and 4 ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Maximum Observed Plasma Concentration (Cmax) of Sunitinib [ Time Frame: 0.5 hour predose and 2, 4, 6, 8, 12, and 24 hours postdose on Day 15 of Cycle 1 ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sunitinib [ Time Frame: 0.5 hour predose and 2, 4, 6, 8, 12, and 24 hours postdose on Day 15 of Cycle 1 ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to 24 Hours Postdose (AUC24) of Sunitinib [ Time Frame: 0.5 hour predose and 2, 4, 6, 8, 12, and 24 hours postdose on Day 15 of Cycle 1 ] [ Designated as safety issue: No ]
    AUC24 is the area under the plasma concentration versus time curve from time zero (predose) to 24 hours postdose (0 to 24).

  • Trough Plasma Concentration (Ctrough) of Sunitinib [ Time Frame: 0.5 hour predose on Day 1 of Cycle 2 ] [ Designated as safety issue: No ]
  • Plasma Concentration at 24 Hours Postdose (C24) of Sunitinib [ Time Frame: 24 hours postdose on Day 15 of Cycle 1 ] [ Designated as safety issue: No ]
  • Number of Participants With Anti-Drug Antibodies (ADA) [ Time Frame: 0.5 hour pre-infusion on Day 1 in Cycles 1 and 2, at end of treatment, and during the last scheduled follow-up visit (5 months from the last dose of study drug) ] [ Designated as safety issue: Yes ]
    Assays for ADA assessment specific for figitumumab would have provided information regarding an immune response to the compound.

  • Number of Participants With Objective Response (OR) [ Time Frame: Baseline, Day 15 of every 2 cycles until disease progression up to follow-up (approximately 28 days following the last dose of study drug) ] [ Designated as safety issue: No ]
    Objective response (OR) was based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. CR was the complete disappearance of all target and non-target disease, no new lesions, or the normalization of markers (if markers were being followed). PR was greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions, no unequivocal progression of non-target disease, no new lesions, or no reappearance of lesions after a CR. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.


Enrollment: 45
Study Start Date: September 2008
Study Completion Date: April 2013
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CP-751,871 + Sunitinib
Escalating cohorts of CP-751,871 + Sunitinib
Drug: CP-751,871
CP-751,871 IV, every 3 weeks
Drug: Sunitinib
Sunitinib - daily dosing

Detailed Description:

The study was closed to enrollment on 14 Jan 2011 and terminated secondary to excessive screen failure rate and for business reasons associated with Pfizer's business decision to stop development of the figitumumab compound. Safety concerns did not contribute to the decision to terminate this clinical trial.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed advanced solid tumors relapsed or refractory to standard therapy or for whom no standard therapy exists.
  • ECOG Performance Status of 0 or 1;
  • Total IGF-1 level ≥100 ng/ml;
  • ECOG Performance Status of 0 or 1
  • Adequate bone marrow, renal, and hepatic function

Exclusion Criteria:

  • Concurrent treatment with any antitumor agents with the exception of LHRH agnosits for prostate cancer patients
  • Treatment with any other investigational therapy within 4 weeks prior to study treatment
  • Major surgery within 4 weeks of study treatment
  • Prior treatment that may increase the risk of cardiac complications
  • Ongoing cardiac dysrhythmias of NCI CTCAE Grade 2 or greater
  • Significant active cardiac disease, including hypertension that cannot be controlled by medications
  • Greater than three (3) prior lines of cytotoxic therapy;
  • Active infection
  • Prior IGF-IR targeted therapy;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00729833

Locations
United States, California
Pfizer Investigational Site
Los Angeles, California, United States, 90095
Pfizer Investigational Site
Santa Monica, California, United States, 90404
United States, Pennsylvania
Pfizer Investigational Site
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
Pfizer Investigational Site
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00729833     History of Changes
Other Study ID Numbers: A4021024
Study First Received: July 30, 2008
Results First Received: April 11, 2014
Last Updated: May 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014