A Phase 2 Study of a Human Anti-PDGFRa Monoclonal Antibody (IMC-3G3) in Previously Treated Patients with Unresectable and/or Metastatic Gastrointestinal Stromal Tumors (GIST)

Phase 2

Completed

Conditions: unresectable and/or metastatic gastrointestinal stromal tumors
tumour in het gastrointestinaltract
10017990
10017991

Registration Number: NL-OMON38170

Lead Sponsor: Imclone Systems

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 3

Inclusion Criteria

1. The patient has histologically or cytologically confirmed, unresectable and/or metastatic GIST.
2. The patient has measurable disease (per RECIST version 1.1).
3. The patient has documented objective progression following, or intolerance to, treatment with at least both imatinib and sunitinib.
4. The patient*s Eastern Cooperative Oncology Group (ECOG) performance status is 0 to 2.
5. The patient has either:
a. prior results from KIT and PDGFRa mutation analysis that meet analytical criteria as defined for the on-study analysis of these mutations (to be confirmed by the central reader for this study) and tumor tissue (from either primary or metastatic tumor [cytology is not acceptable]) that can be submitted for analysis within 30 days after the first dose of study therapy; or
b. if prior results from KIT and PDGFRa mutation analysis are not available or do not meet analytical criteria as above, then tumor tissue (from either primary or metastatic tumor [cytology is not acceptable]) must be submitted for genotype testing at the latest 28 days prior to the first dose of study therapy. The results from the Central Lab need to be available prior to enrolling the patient.
6. The patient*s age at registration is >= 18 years.
7. The patient has adequate hematologic function as defined by an absolute neutrophil count (ANC) >= 1500/µL, hemoglobin >= 9.0 g/dL (5.58 mmol/L), and a platelet count of >= 75,000/µL obtained within 2 weeks prior to registration.
8. The patient has adequate hepatic function as defined by a total bilirubin <= 1.5 mg/dL (25.65 µmol/L), and aspartate transaminase (AST) and alanine transaminase (ALT) <= 3.0 × the upper limit of normal (ULN) [or <= 5.0 x the ULN in the setting of liver metastases].
9. The patient has adequate renal function (serum creatinine <= 1.5 × the institutional ULN or calculated creatinine clearance >= 45 mL/min.
10. The patient has adequate coagulation function, as defined by international normalized ratio (INR) <= 1.5 and a partial thromboplastin time (PTT) <= 1.5 × ULN if not receiving anticoagulation therapy. Patients on full dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin, have a therapeutic INR, no active bleeding (defined as within 14 days prior to first dose of study medication), and no pathological condition that carries a high risk of bleeding (eg, tumor involving major vessels or known varices).
11. 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 at least 12 weeks after the last dose of IMC-3G3.
12. The patient has resolution to Grade <= 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0 of all clinically significant toxic effects of prior locoregional therapy, surgery, chemoembolization, or other anticancer therapy. The exception for such effects are events that pertain to the lab values found elsewhere in these inclusion criteria. (For example, criterion #7 states that a patient with hemoglobin >= 9.0 g/dL [5.58 mmol/L] is considered eligible, even though NCI-CTCAE Version 4.0 defines this value as Grade 2 anemia.)
13. The patient has a life expectancy of >= 3 months.
14. The patient has provided signed informed consent

Exclusion Criteria

1. The patient has untreated central nervous system metastases and as a result is clinically unstable with regard to neurologic function. Patients are eligible if the following conditions are met: a) surgical resection performed at least 4 weeks prior to registration; b) at least 4 weeks have elapsed since completion of cranial irradiation (whole brain radiation therapy, focal radiation therapy, stereotactic radiosurgery); c) at least 4 weeks have elapsed since the last steroid dose; and d) central nervous system metastases are stable.
2. The patient has a history of another primary cancer, with the exception of a) curatively resected non-melanomatous skin cancer; b) curatively treated 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.
3. The patient has received any investigational therapy within 14 days prior to registration or is concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
4. The patient is receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, targeted therapy, chemoembolization, or an investigational agent.
5. The patient has an elective or a planned major surgery to be performed during the course of the study.
6. 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, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
7. The patient has unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months prior to study entry.
8. The patient has known human immunodeficiency virus (HIV) infection.
9. The patient has undergone major surgery within 28 days prior to registration.
10. The patient, if female, is pregnant or breastfeeding.
11. The patient has a known allergy to any of the treatment components.
12. The patient has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of IMC-3G3.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Efficacy assessments will include imaging studies and tumor<br /><br>measurements/disease response assessments, according to RECIST 1.1, every 6<br /><br>weeks (± 3 days) following the first dose of study therapy until documentation<br /><br>of PD.</p><br>

Secondary Outcome Measures