A Study of IMC-3G3 in Soft Tissue Sarcoma

Sarcoma, Soft Tissue Clinical Trial

Official title:

A Phase 1b/2 Randomized Phase 2 Study Evaluating the Efficacy of Doxorubicin With or Without a Human Anti-PDGFRα Monoclonal Antibody (IMC-3G3) in the Treatment of Advanced Soft Tissue Sarcoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01185964
• Other study ID #: 14055
• Secondary ID: I5B-IE-JGDGCP15-
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: August 19, 2010
• Last updated: February 13, 2015
• Start date: October 2010
• Est. completion date: March 2016

Study information

• Verified date: February 2015
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to gather information about the use of an investigational drug called IMC-3G3 with a drug for soft tissue sarcoma called doxorubicin.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 146
• Est. completion date: March 2016
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• The patient has histologically- or cytologically-confirmed malignant soft tissue sarcoma (STS), including uterine leiomyosarcoma

• The patient has advanced STS, not amenable to treatment with surgery or radiotherapy

• The patient's Eastern Cooperative Oncology Group (ECOG) performance status is 0-2

• The patient has available tumor tissue from either the primary or metastatic tumor for determination of PDGFRa expression

• The patient has adequate hematologic function as defined by an absolute neutrophil count (ANC) = 1500 µL, hemoglobin = 9.0 g/dL, and a platelet count of 100,000/µL obtained within 2 weeks prior to study entry

• The patient has adequate hepatic function as defined by a total bilirubin = 1.5 mg/dL, and aspartate transaminase (AST) and alanine transaminase (ALT) = 3.0 times the upper limit of normal (ULN)

• The patient has adequate renal function as defined by serum creatinine = 1.5 × the institutional ULN. If creatinine is above the ULN, the patient's creatinine clearance is = 45 mL/min

• The patient has urinary protein = 1+ on dipstick or routine urinalysis; if urine dipstick or routine analysis is = 2+, a 24-hour urine for protein must demonstrate < 1 g of protein in 24 hours to allow participation

• Because the teratogenicity of IMC-3G3 is not known, women of childbearing potential (WOCBP) and sexually active males must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation

Exclusion Criteria:

• The patient has histologically- or cytologically-confirmed Kaposi's sarcoma

• The patient has untreated central nervous system metastases

• The patient received prior treatment with doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones (ie, mitoxantrone)

• The patient received prior radiation therapy to the mediastinal/pericardial area

• The patient has a history of another primary cancer, with the exception of a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor treated with curative intent, no known active disease present, and no treatment administered during the last 3 years prior to study entry

• The patient is receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemo-embolization, targeted therapy, or an investigational agent

• The patient has an elective or a planned major surgery to be performed during the course of the study

• The patient has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, requiring parenteral antibiotics, symptomatic congestive heart failure, severe myocardial insufficiency, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• The patient has unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months prior to study entry

• The patient has known immunodeficiency virus (HIV) infection

• The patient, if female, is pregnant or lactating

• The patient has a known allergy to any of the treatment components

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sarcoma
• Sarcoma, Soft Tissue

Intervention

Biological:
• IMC-3G3
IMC-3G3 15 mg/kg by intravenous transfusion (I.V.) on days 1+8 of a 21-day cycle

Drug:
• doxorubicin
Doxorubicin 75 mg/m2 by intravenous injection on day 1 of the 21-day cycle.
• dexrazoxane
Dexrazoxane given at 750 mg/m2 by intravenous injection on day 1 of the 21-day cycle prior to administration of each doxorubicin infusion during cycles 5-8 for prevention of cardiotoxicity.

Locations

Country	Name	City	State
United States	ImClone Investigational Site	Atlanta	Georgia
United States	ImClone Investigational Site	Aurora	Colorado
United States	ImClone Investigational Site	Charleston	South Carolina
United States	ImClone Investigational Site	Charlotte	North Carolina
United States	ImClone Investigational Site	Chicago	Illinois
United States	ImClone Investigational Site	Cleveland	Ohio
United States	ImClone Investigational Site	Gainesville	Florida
United States	ImClone Investigational Site	Los Angeles	California
United States	ImClone Investigational Site	Madison	Wisconsin
United States	ImClone Investigational Site	Memphis	Tennessee
United States	ImClone Investigational Site	New York	New York
United States	ImClone Investigational Site	Orlando	Florida
United States	ImClone Investigational Site	Rochester	Minnesota
United States	ImClone Investigational Site	San Antonio	Texas
United States	ImClone Investigational Site	Seattle	Washington
United States	ImClone Investigational Site	St Louis	Missouri
United States	ImClone Investigational Site	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	PFS is the primary outcome for the Phase 2 portion of the study. PFS is measured from the date of randomization until the first radiographic documentation of objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) or death from any cause.	23 months	No
Primary	Summary of Safety for the Phase 1b Portion of the Study		up to 24 weeks	Yes
Secondary	Overall Survival (OS)	Date of randomization to the date of death from any cause	23 months	No
Secondary	Percentage of Participants with Objective Response (Objective Response Rate)	Percentage of participants achieving a best overall response of partial or complete response (PR + CR), according to RECIST from the start of treatment until disease progression or occurrence.	23 months	No
Secondary	Pharmacokinetic (PK) Profile of IMC-3G3		up to week 24	No
Secondary	Proportion of Participants Who are Progression-free (PFS) at 3 Months	The 3 month progression-free survival (PFS) rate is defined as the proportion of participants that are alive and progression-free 3 months after randomization. PFS is measured from the date of randomization until the first radiographic documentation of objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) or death from any cause.	3 months	No