Clinical trial NCT01316263: A Study of Olaratumab (IMC-3G3) in Previously Treated Participants With Unresectable and/or Metastatic Gastrointestinal Stromal Tumors
Official title: A Phase 2 Study of a Human Anti-PDGFRα Monoclonal Antibody (IMC-3G3) in Previously Treated Patients With Unresectable and/or Metastatic Gastrointestinal Stromal Tumors (GIST)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumor (GIST)
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-03-16
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the tumor response of stable disease (SD), partial response (PR), or complete response (CR) \[according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1 criteria)\] at 12 weeks in participants with Gastrointestinal Stromal Tumors (GIST) harboring platelet-derived growth factor receptor alpha (PDGFRα) mutations and patients with GIST not harboring PDGFRα mutations.


Eligibility criteria: Inclusion Criteria:

* Participant has histologically or cytologically confirmed, unresectable and/or metastatic GIST
* Participant has measurable disease
* Participant has documented objective progression following, or intolerance to, treatment with both imatinib and sunitinib
* Participant's Eastern Cooperative Oncology Group (ECOG) performance status (PS) is 0 to 2
* Participant has either:

  1. prior results from growth factor receptor associated with tyrosine kinase activity (KIT) and PDGFRα mutation analysis that meet analytical criteria as defined for the on-study analysis of these mutations and tumor tissue (from either primary or metastatic tumor) that can be submitted for analysis within 30 days after the first dose of study therapy; or
  2. if prior results from KIT and PDGFRα mutation analysis are not available or do not meet analytical criteria as above, then tumor tissue (from either primary or metastatic tumor) must be submitted for genotype testing at the latest 28 days prior to the first dose of study therapy
* Participant has adequate hematologic, hepatic, renal and coagulation function
* Women of childbearing potential and sexually active males must agree to use adequate contraception prior to study and for at least 12 weeks after the last dose of IMC-3G3
* Participant has a life expectancy of ≥ 3 months

Exclusion Criteria:

* Participant has untreated central nervous system metastases, and as a result, is clinically unstable with regard to neurologic function
* Participant has a history of another primary cancer
* Participant has received any investigational therapy within 14 days prior to registration, or is currently enrolled in any other type of medical research
* Participant is receiving concurrent treatment with other anticancer therapy
* Participant has known human immunodeficiency virus (HIV) infection
* Participant has undergone major surgery within 28 days prior to registration
* If female, participant is pregnant or breastfeeding

Primary outcomes:
measure: Percentage of Participants With Tumor Response of Stable Disease (SD), Partial Response (PR) or Complete Response (CR) (Clinical Benefit Rate) at 12 Weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Baseline to the first date of objectively determined PD or death from any cause up to 35.9 weeks
measure: Percentage of Participants With CR or PR [Radiographic Objective Response Rate (ORR)]
timeFrame: Baseline up to 35.9 weeks and post study discontinuation 30-day follow-up
measure: Overall Survival (OS)
timeFrame: Date of first dose of study drug to the date of death from any cause up to 57.3 weeks
measure: Number of Participants With Adverse Events (AE) and Participants Who Died
timeFrame: Baseline up to 57.3 weeks and 30-day post study-discontinuation follow-up
measure: Percentage of Participants With CR, PR or SD [Disease Control Rate (DCR)]
timeFrame: Baseline up to 35.9 weeks
measure: Maximum Concentration (Cmax)
timeFrame: Day 1 of Cycles 1 and 3 (14-day cycles)
measure: Area Under the Curve (AUC)
timeFrame: Day 1 of Cycles 1 and 3 (14-day cycles)
measure: Half Life (t½)
timeFrame: Day 1 of Cycles 1 and 3 (14-day cycles)
measure: Clearance (CL)
timeFrame: Day 1 of Cycles 1 and 3 (14-day cycles)
measure: Volume of Distribution at Steady State (Vss)
timeFrame: Day 1 of Cycles 1 and 3 (14-day cycles)
measure: Percentage of Participants With Human Anti-Olaratumab (IMC-3G3) Antibody Results
timeFrame: Day 1 of Cycles 1, 3, 6, 12 and 18 prior to infusion (14-day cycles)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: ImClone Investigational Site
state: Illinois
city: Boston
country: United States
facility: ImClone Investigational Site
state: Massachusetts
city: Edegem
country: Belgium
facility: ImClone Investigational Site
city: Leuven
country: Belgium
facility: ImClone Investigational Site
city: Bad Saarow
country: Germany
facility: ImClone Investigational Site
city: Berlin
country: Germany
facility: ImClone Investigational Site
city: Essen
country: Germany
facility: ImClone Investigational Site
city: Mannheim
country: Germany
facility: ImClone Investigational Site
city: Tuebingen
country: Germany
facility: ImClone Investigational Site
city: Leiden
country: Netherlands
facility: ImClone Investigational Site
city: Warsaw
country: Poland
facility: ImClone Investigational Site
city: Madrid
country: Spain
facility: ImClone Investigational Site
city: Madrid
country: Spain
facility: ImClone Investigational Site
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Wagner AJ, Kindler H, Gelderblom H, Schoffski P, Bauer S, Hohenberger P, Kopp HG, Lopez-Martin JA, Peeters M, Reichardt P, Qin A, Nippgen J, Ilaria RL, Rutkowski P. A phase II study of a human anti-PDGFRalpha monoclonal antibody (olaratumab, IMC-3G3) in previously treated patients with metastatic gastrointestinal stromal tumors. Ann Oncol. 2017 Mar 1;28(3):541-546. doi: 10.1093/annonc/mdw659.