Figitumumab Combined With Pegvisomant For Advanced Solid Tumors

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

Detailed Description
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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.

Official Title
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Phase 1 Safety And Tolerability Study Of Figitumumab Combined With Pegvisomant In Patients With Advanced Solid Tumors

Conditions
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Colorectal Neoplasms, Lung Neoplasms, Breast Neoplasms, Prostatic Neoplasms, Sarcoma

Intervention / Treatment
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* Drug: figitumumab
* Drug: pegvisomant


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: figitumumab<br>* IGF-1R antibody, 20 mg/kg, IV every 3 weeks for up to 1 year<br>* Other names: CP-751,871;Drug: pegvisomant<br>* growth hormone antagonist, 10, 20 or 30 mg per day via subcutaneous injection for up to 1 year<br>* Other names: Somavert;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | From Cycle 2, Day 1 to Cycle 3, Day 8; from Cycle 1, Day 15 to end of Cycle 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 |  | Cycle 1: Day 1 (within 2 hours before figitumumab infusion), Day 2 (1 hour post figitumumab infusion), Day 8 and Day 15 | 
| Maximum Observed Plasma Concentration (Cmax) of Figitumumab |  | 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 |  | 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. | 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. | 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 | 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. | 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. | 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. | 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. | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced solid tumors cancer refractory cancer figitumumab pegvisomant