Clinical trial NCT00768391: Study of IMC-3G3 in Patients With Tumors That Are Not Responding to Standard Therapies or No Therapy is Available
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Tumors
Lymphoma
Antibodies, Monoclonal
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2008-10-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: 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.

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 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.

Primary outcomes:
measure: Summary of Participants Reporting Adverse Events
timeFrame: Approximately 36 months
measure: Maximum Tolerated Dose (MTD)
timeFrame: Approximately 36 months
Secondary outcomes:
measure: Pharmacokinetics
timeFrame: 6 weeks
measure: Anti-IMC-3G3 Antibody Assessment
timeFrame: Approximately 36 months
measure: Antitumor Activity of IMC-3G3 as Monotherapy
timeFrame: 6 weeks
measure: Pharmacodynamics
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: ImClone Investigational Site
state: Indiana
city: Houston
country: United States
facility: ImClone Investigational Site
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: E-mail: ClinicalTrials@ ImClone.com
role: STUDY_DIRECTOR
References: