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

This study has been completed.
Sponsor:
Information provided by:
ImClone LLC
ClinicalTrials.gov Identifier:
NCT00768391
First received: October 6, 2008
Last updated: June 27, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Solid Tumors
Biological: IMC-3G3
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: 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

Resource links provided by NLM:


Further study details as provided by ImClone LLC:

Primary Outcome Measures:
  • Summary of Participants Reporting Adverse Events [ Time Frame: Approximately 36 months ] [ Designated as safety issue: Yes ]
  • Maximum Tolerated Dose (MTD) [ Time Frame: Approximately 36 months ] [ Designated as safety issue: Yes ]
    After all patients complete a cohort, toxicity data is reviewed before the next cohort of patients is treated at the next higher dose level


Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Anti-IMC-3G3 Antibody Assessment [ Time Frame: Approximately 36 months ] [ Designated as safety issue: No ]
  • Antitumor Activity of IMC-3G3 as Monotherapy [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Pharmacodynamics [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: December 2006
Study Completion Date: January 2010
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00768391

Locations
United States, Indiana
ImClone Investigational Site
Indianapolis, Indiana, United States, 46282
United States, Texas
ImClone Investigational Site
Houston, Texas, United States, 77030
Sponsors and Collaborators
ImClone LLC
Investigators
Study Director: E-mail: ClinicalTrials@ ImClone.com ImClone LLC
  More Information

No publications provided

Responsible Party: Chief Medical Officer, ImClone LLC
ClinicalTrials.gov Identifier: NCT00768391     History of Changes
Other Study ID Numbers: 13937, CP15-0601, I5B-IE-JGDC
Study First Received: October 6, 2008
Last Updated: June 27, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by ImClone LLC:
Tumors
Lymphoma
Antibodies, Monoclonal

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on September 30, 2014