Figitumumab Combined With Pegvisomant For Advanced Solid Tumors

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00976508
First received: September 10, 2009
Last updated: October 23, 2013
Last verified: October 2013
  Purpose

This is a Phase 1 study investigating the safety and tolerability of Figitumumab plus Pegvisomant for treatment of advanced solid tumors.


Condition Intervention Phase
Colorectal Neoplasms
Lung Neoplasms
Breast Neoplasms
Prostatic Neoplasms
Sarcoma
Drug: figitumumab
Drug: pegvisomant
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 Safety And Tolerability Study Of Figitumumab Combined With Pegvisomant 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 Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From Screening to the follow-up visit (90 days after last dose of figitimumab) ] [ Designated as safety issue: Yes ]
    Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. AEs were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 (Grade [Gr] 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death). Relatedness to [study drug] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.

  • Number of Participants With Dose Limiting Toxicities (DLT) [ Time Frame: From Cycle 2, Day 1 to Cycle 3, Day 8; from Cycle 1, Day 15 to end of Cycle 2 ] [ Designated as safety issue: Yes ]
    DLT was defined as any of the following events occurring during DLT period and considered related to study medication: Grade (Gr) 4 neutropenia lasting >=7 days, febrile neutropenia (Gr 3 or 4 neutropenia, fever >=38.5 degrees Celsius, lasting over 24 hours), neutropenic infection (Gr >=3 neutropenia, infection); Gr 3 or 4 thrombocytopenia associated with bleeding or Gr 4 thrombocytopenia >=7 days; Gr 3 or 4 lymphopeniab accompanied by an opportunistic infection; other non-hematologic Grade 4 toxicities or symptomatic Gr 3 toxicities that require medical intervention and 14 days to resolve.


Secondary Outcome Measures:
  • Serum Circulating Insulin-like Growth Factor (IGF-1) Levels [ Time Frame: Days 1 and 15 of Cycle 1 (Baseline); Day 1 of subsequent cycles starting from Cycle 2 to Cycle 27; end of treatment (21 days after last dose of figitumumab); follow-up visit (90 days after last dose of figitumumab) ] [ Designated as safety issue: No ]
    The effect of the combined therapy with figitumumab and pegvisomant on circulating concentrations of total IGF-1 was assessed.

  • Cycle 1: Maximum Observed Plasma Concentration (Cmax) of Figitumumab [ Time Frame: Cycle 1: Day 1 (within 2 hours before figitumumab infusion), Day 2 (1 hour post figitumumab infusion), Day 8 and Day 15 ] [ Designated as safety issue: No ]
  • Maximum Observed Plasma Concentration (Cmax) of Figitumumab [ Time Frame: Cycle 2: Day 1 (within 2 hours before and 1 hour after figitumumab infusion); Cycle 3 to Cycle 17: Day 1 (within 2 hours before figitumumab infusion); end of treatment; 90-day follow-up visit ] [ Designated as safety issue: No ]
  • Cycle 1: Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab [ Time Frame: Cycle 1: Day 1 (within 2 hours before figitumumab infusion), Day 2 (1 hour post figitumumab infusion), Day 8 and Day 15 ] [ Designated as safety issue: No ]
  • Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab [ Time Frame: Cycle 2: Day 1 (within 2 hours before and 1 hour after figitumumab infusion); Cycle 3 to Cycle 17: Day 1 (within 2 hours before figitumumab infusion); end of treatment; 90-day follow-up visit ] [ Designated as safety issue: No ]
    Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab from Cycle 2 to the end of treatment.

  • Cycle 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Figitumumab [ Time Frame: Days 1, 2, 8 and 15 of Cycle 1; Day 1 of subsequent cycle starting from Cycle 2 (up to Cycle 17); end of treatment ( 21 days after last dose of figitumumab); follow-up visit (90 days after last dose of figitumumab) ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) of figitumumab in cycle 1.

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)of Figitumumab [ Time Frame: Cycle 2: Day 1 (within 2 hours before and 1 hour after figitumumab infusion); Cycle 3 to Cycle 17: Day 1 (within 2 hours before figitumumab infusion); end of treatment; 90-day follow-up visit ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)of figitumumab after Cycle 1

  • Area Under the Trough Concentrations (AUCtrough) [ Time Frame: Cycle 1: Day 15 (within 2 hours before loading dose), Day 16 (within 2 hours pre-SC dose); Cycle 2: Days 1, 8 and 15 (within 2 hours pre-SC dose); Cycle 3 up to Cycle 17: Day 1 (within 2 hours pre-SC dose); end of treatment; 90-day follow-up visit ] [ Designated as safety issue: No ]
    The trough concentration-time profile (AUCtrough) of pegvisomant was to be analyzed by noncompartmental methods.

  • Mean Change in Glucose Levels Between Fasting and Post Glucose Load [ Time Frame: Screening; Day 8 of Cycle 1; Day 15 of Cycle 2 ] [ Designated as safety issue: No ]
    The effect of combining figitumumab with pegvisomant was analyzed to assess whether pegvisomant reverses figitumumab-induced glucose intolerance at various pegvisomant dose levels. The change in glucose load was assessed by Glucose Tolerance Testing (GTT) at baseline (fasting), during Cycle 1 following administration of figitumumab alone (post load), and near the end of Cycle 2 (post load) following combined therapy with figitumumab and pegvisomant.

  • Percentage of Participants Reporting Positive Anti-Drug Antibodies (ADA) Response for Figitumumab [ Time Frame: Day 1 of Cycles 1 and 4; end of treatment (21 days after last dose of figitumumab); follow-up visit (90 days after last dose of figitumumab) ] [ Designated as safety issue: No ]
    Percentage of participants with positive total or neutralizing ADA for figitumumab.

  • Number of Participants With Objective Response [ Time Frame: From Screening, odd numbered cycles (predose, Cycle 3, 5, 7 etc.) up to Cycle 27 or end of treatment visit (21 days after last dose of figitumumab) ] [ Designated as safety issue: No ]
    Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST)version 1.1. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST version 1.1. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.


Enrollment: 24
Study Start Date: November 2009
Study Completion Date: October 2012
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: figitumumab
IGF-1R antibody, 20 mg/kg, IV every 3 weeks for up to 1 year
Other Name: CP-751,871
Drug: pegvisomant
growth hormone antagonist, 10, 20 or 30 mg per day via subcutaneous injection for up to 1 year
Other Name: Somavert

Detailed Description:

This study was closed to enrollment on 18 April 2011 due to inability to recruit patients on a timely basis as well as business reasons. Study closure was not related to any safety concerns.

  Eligibility

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients ≥18 years of age with advanced solid tumors for which the combination of figitumumab and pegvisomant are reasonable treatment options.
  • Patients between the ages of 10 and 18 years with advanced sarcomas for which there is no available curative therapy or therapy proven to prolong survival with an acceptable quality of life will be included in the Sarcoma Expansion Cohort.
  • Adequate recovery from prior therapies.
  • Adequate organ function (i.e. bone marrow, kidney, liver)
  • Total IGF-1 ≥100 ng/ml (13 nmol/L).

Exclusion Criteria:

  • Concurrent treatment with any anti-tumor agents.
  • Pregnant or breastfeeding females.
  • Significant past history or active cardiac disease
  • Active infection
  • History of diabetes mellitus.
  • Glycosylated hemoglobin >5.7
  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: NCT00976508

Locations
United States, Minnesota
Pfizer Investigational Site
Minneapolis, Minnesota, United States, 55455
Pfizer Investigational Site
Rochester, Minnesota, United States, 55905
Canada, Quebec
Pfizer Investigational Site
Montreal, Quebec, Canada, H3T 1E2
Finland
Pfizer Investigational Site
Helsinki, Finland, 00290
Germany
Pfizer Investigational Site
Muenster, Germany, 48149
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: NCT00976508     History of Changes
Other Study ID Numbers: A4021040
Study First Received: September 10, 2009
Results First Received: October 23, 2013
Last Updated: October 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
advanced solid tumors cancer refractory cancer figitumumab pegvisomant

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Colorectal Neoplasms
Lung Neoplasms
Prostatic Neoplasms
Sarcoma
Neoplasms by Site
Breast Diseases
Skin Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Prostatic Diseases
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 14, 2014