This is a Phase 1 study investigating the safety and tolerability of Figitumumab plus Pegvisomant for treatment of advanced solid tumors.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
IGF-1R antibody, 20 mg/kg, IV every 3 weeks for up to 1 year
growth hormone antagonist, 10, 20 or 30 mg per day via subcutaneous injection for up to 1 year
Pfizer Investigational Site
Minneapolis, Minnesota, United States
Pfizer Investigational Site
Rochester, Minnesota, United States
Pfizer Investigational Site
Montreal, Quebec, Canada
Pfizer Investigational Site
Helsinki, Finland
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: From Screening to the follow-up visit (90 days after last dose of figitimumab)
Number of Participants With Dose Limiting Toxicities (DLT)
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.
Time frame: From Cycle 2, Day 1 to Cycle 3, Day 8; from Cycle 1, Day 15 to end of Cycle 2
Serum Circulating Insulin-like Growth Factor (IGF-1) Levels
The effect of the combined therapy with figitumumab and pegvisomant on circulating concentrations of total IGF-1 was assessed.
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)
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Pfizer Investigational Site
Münster, Germany
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
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
Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab
Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab from Cycle 2 to the end of treatment.
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
Cycle 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Figitumumab
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) of figitumumab in cycle 1.
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)
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)of Figitumumab
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)of figitumumab after Cycle 1
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
Area Under the Trough Concentrations (AUCtrough)
The trough concentration-time profile (AUCtrough) of pegvisomant was to be analyzed by noncompartmental methods.
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
Mean Change in Glucose Levels Between Fasting and Post Glucose Load
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.
Time frame: Screening; Day 8 of Cycle 1; Day 15 of Cycle 2
Percentage of Participants Reporting Positive Anti-Drug Antibodies (ADA) Response for Figitumumab
Percentage of participants with positive total or neutralizing ADA 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)
Number of Participants With Objective Response
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.
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)