Study of IMC-3G3 in Patients With Tumors That Are Not Responding to Standard Therapies or No Therapy is Available

Phase I Study of Anti-Platelet Derived Growth Factor Receptor Alpha (PDGFRa) Monoclonal Antibody IMC-3G3 in Patients With Advanced Solid Tumors Who No Longer Respond to Standard Therapy or for Whom no Standard Therapy is Available

The purpose of this study is to determine if IMC-3G3 is safe for patients, and also to determine the best dose of IMC-3G3 to give to patients.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Biological: IMC-3G3

Detailed Description

The purpose of this study is to establish the safety profile and maximum tolerated dose (MTD) of the anti-PDGFRα monoclonal antibody IMC-3G3 in patients with advanced solid tumors who no longer respond to standard therapy or for whom no standard therapy is available.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46282
      • ImClone Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • ImClone Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histopathological-documented, measurable, or non measurable, advanced primary tumor or recurrent solid tumor or lymphoma unresponsive to standard therapy or for which there is no standard therapy available.
2. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2 at study entry.
3. Able to provide written informed consent.
4. Age 18 years or older.
5. Life expectancy of > 3 months.
6. Adequate hematologic function, as defined by: an absolute neutrophil count ≥ 1500/mm3; a platelet count ≥ 100,000/mm3
7. Adequate hepatic function, as defined by: a total bilirubin level ≤ 1.5 x the upper limit of normal (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2.5 x the ULN or ≤ 5 x the ULN if known liver metastases
8. Adequate renal function, as defined by serum creatinine level ≤ 1.5 x the ULN.
9. Uses effective contraception (per the institutional standard), if procreative potential exists.
10. Adequate recovery from recent surgery, chemotherapy, and radiation therapy.
11. Accessible for treatment and follow-up, must be treated at the participating center.

Exclusion Criteria:

1. Received chemotherapy or therapeutic radiotherapy 28 days prior to the first dose of study medication or has ongoing side effects ≥ grade 2 due to agents administered more than 28 days earlier.
2. Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection requiring parenteral antibiotics; symptomatic congestive heart failure; unstable angina pectoris, angioplasty, stenting, or myocardial infarction 6 months prior to the first dose of study medication; uncontrolled hypertension; clinically significant cardiac arrhythmia including but not limited to: multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment or asymptomatic sustained ventricular tachycardia; uncontrolled diabetes; psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements
3. Progressive or symptomatic brain metastases
4. Has a serious or nonhealing active wound, ulcer, or bone fracture.
5. Known human immunodeficiency virus positivity.
6. Major surgical procedure, an open biopsy, or a significant traumatic injury 28 days prior to treatment.
7. Is currently or has recently used (28 days prior to) a thrombolytic agent.
8. Currently using full-dose warfarin (an exception is low-dose warfarin to maintain patency of pre-existing, permanent, indwelling intravenous [I.V.] catheters; for patients receiving warfarin, the international normalized ratio [INR] should be < 1.5). A patient requiring heparin is excluded.
9. Undergoes chronic daily treatment with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function (cyclooxygenase-2 [COX-2] inhibitors are permitted).
10. Has a history or clinical evidence of a deep venous or arterial thrombosis (including pulmonary embolism) 6 months prior to the first dose of study medication.
11. Has proteinuria ≥ 2+ by routine urinalysis
12. Pregnancy (confirmed by serum beta human chorionic gonadotropin) or lactating
13. Received prior treatment with agents targeting the PDGFR ligand or receptor 6 weeks prior to the first dose of study medication.
14. Received prior treatment with monoclonal antibodies 6 weeks prior to the first dose of study medication.
15. Has a history of allergic reactions to monoclonal antibodies or other therapeutic proteins.

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IMC-3G3; All patients will receive intravenous infusions of IMC-3G3, with the dose depending on which cohort they are enrolled into.	Biological: IMC-3G3; Intravenously, once every week for Cohorts 1 through 3 and once every other week for Cohorts 4 and 5. Starting dose will be 4mg/kg in Cohort 1, with dose doubling between cohorts. Dose escalation of 100% (2 x previous dose) Dose escalation increment reduced to 33% (1.33 x previous dose). Cohorts 4 and 5 will receive 15mg/kg and 20mg/kg, intravenously, once every other week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary of Participants Reporting Adverse Events		Approximately 36 months
Maximum Tolerated Dose (MTD)	After all patients complete a cohort, toxicity data is reviewed before the next cohort of patients is treated at the next higher dose level	Approximately 36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics	6 weeks
Anti-IMC-3G3 Antibody Assessment	Approximately 36 months
Antitumor Activity of IMC-3G3 as Monotherapy	6 weeks
Pharmacodynamics	6 weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: E-mail: ClinicalTrials@ ImClone.com, Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: October 6, 2008
• First Submitted That Met QC Criteria: October 7, 2008
• First Posted (Estimate): October 8, 2008

Study Record Updates

• Last Update Posted (Estimate): June 28, 2011
• Last Update Submitted That Met QC Criteria: June 27, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: Lymphoma; Tumors; Antibodies, Monoclonal
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Olaratumab
• Other Study ID Numbers: 13937; CP15-0601 (Other Identifier: ImClone, LLC); I5B-IE-JGDC (Other Identifier: Eli Lilly and Company)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No