Figitumumab Combined With Pegvisomant For Advanced Solid Tumors

Breast Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00976508
• Other study ID #: A4021040
• Status: Terminated
• Phase: Phase 1
• First received: September 10, 2009
• Last updated: October 23, 2013
• Start date: November 2009
• Est. completion date: October 2012

Study information

• Verified date: October 2013
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: October 2012
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Colorectal Neoplasms
• Lung Neoplasms
• Neoplasms
• Prostatic Neoplasms
• Sarcoma

Intervention

Drug:
• figitumumab
IGF-1R antibody, 20 mg/kg, IV every 3 weeks for up to 1 year
• pegvisomant
growth hormone antagonist, 10, 20 or 30 mg per day via subcutaneous injection for up to 1 year

Locations

Country	Name	City	State
Canada	Pfizer Investigational Site	Montreal	Quebec
Finland	Pfizer Investigational Site	Helsinki
Germany	Pfizer Investigational Site	Muenster
United States	Pfizer Investigational Site	Minneapolis	Minnesota
United States	Pfizer Investigational Site	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada,  Finland,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Primary	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	Yes
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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)	No

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