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

Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00768391
• Other study ID #: 13937
• Secondary ID: CP15-0601I5B-IE-
• Status: Completed
• Phase: Phase 1
• First received: October 6, 2008
• Last updated: June 27, 2011
• Start date: December 2006
• Est. completion date: January 2010

Study information

• Verified date: June 2011
• Source: ImClone LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 2010
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Solid Tumors

Intervention

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.

Locations

Country	Name	City	State
United States	ImClone Investigational Site	Houston	Texas
United States	ImClone Investigational Site	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
ImClone LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Summary of Participants Reporting Adverse Events		Approximately 36 months	Yes
Primary	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	Yes
Secondary	Pharmacokinetics		6 weeks	No
Secondary	Anti-IMC-3G3 Antibody Assessment		Approximately 36 months	No
Secondary	Antitumor Activity of IMC-3G3 as Monotherapy		6 weeks	No
Secondary	Pharmacodynamics		6 weeks	Yes