A Study of Olaratumab (IMC-3G3) in Previously Treated Participants With Unresectable and/or Metastatic Gastrointestinal Stromal Tumors

NCT01316263 | Terminated Phase 2 Results

• 4 other identifiers: 14244CP15-1008I5B-IE-JGDH2010-022560-12
• Study Type: interventional
• Target: 21
• Locations: 6 countries
• Sites: 13

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.

Conditions

Gastrointestinal Stromal Tumor (GIST)

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Tumor Response of Stable Disease (SD), Partial Response (PR) or Complete Response (CR) (Clinical Benefit Rate) at 12 Weeks

  Clinical benefit was defined as CR, PR, or SD using Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST, v1.1) criteria. CR: disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to \<10 millimeters (mm). PR: ≥30% decrease in sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. SD: neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. PD: increase ≥20% in sum of the diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if that was the smallest on study). Sum must also have demonstrated an absolute increase of ≥5 mm, or appearance of 1 or more new lesions was considered progression. Percentage of participants=(participants with CR+PR+SD/participants in group) \*100.

  12 weeks

Secondary Outcomes (11)

• Progression-Free Survival (PFS)

  Baseline to the first date of objectively determined PD or death from any cause up to 35.9 weeks

• Percentage of Participants With CR or PR [Radiographic Objective Response Rate (ORR)]

  Baseline up to 35.9 weeks and post study discontinuation 30-day follow-up

• Overall Survival (OS)

  Date of first dose of study drug to the date of death from any cause up to 57.3 weeks

• Number of Participants With Adverse Events (AE) and Participants Who Died

  Baseline up to 57.3 weeks and 30-day post study-discontinuation follow-up

• Percentage of Participants With CR, PR or SD [Disease Control Rate (DCR)]

  Baseline up to 35.9 weeks

Study Arms (2)

PDGFRα mutation negative

EXPERIMENTAL

Participants with GIST with genotypes that do not have a PDGFRα mutation given 20 milligrams per kilogram (mg/kg) Olaratumab intravenously (IV) every 14 days.

Biological: Olaratumab

PDGFRα mutation positive

EXPERIMENTAL

Participants with GIST with genotypes that have a PDGFRα mutation given 20 mg/kg Olaratumab IV every 14 days.

Biological: Olaratumab

Interventions

Olaratumab BIOLOGICAL

Administered IV

Also known as: LY3012207, IMC-3G3

PDGFRα mutation negative; PDGFRα mutation positive

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (13)

ImClone Investigational Site

Chicago, Illinois, 60637, United States

Location

ImClone Investigational Site

Boston, Massachusetts, 02215, United States

Location

ImClone Investigational Site

Edegem, B-2650, Belgium

Location

ImClone Investigational Site

Leuven, B-3000, Belgium

Location

ImClone Investigational Site

Bad Saarow, 15526, Germany

Location

ImClone Investigational Site

Berlin, 13125, Germany

Location

ImClone Investigational Site

Essen, 45122, Germany

Location

ImClone Investigational Site

Mannheim, 68167, Germany

Location

ImClone Investigational Site

Tübingen, 72076, Germany

Location

ImClone Investigational Site

Leiden, 2300 RC, Netherlands

Location

ImClone Investigational Site

Warsaw, 02-781, Poland

Location

ImClone Investigational Site

Madrid, 28041, Spain

Location

ImClone Investigational Site

Madrid, 28050, Spain

Location

Related Publications (1)

• 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.

  PMID: 28426120 DERIVED

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

olaratumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Limitations and Caveats

The development of olaratumab (IMC-3G3) was put on hold in this indication due to reasons not related to efficacy and/or safety, Stage 2 of this study was not completed and trial terminated due to poor accrual.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2011
• First Posted: March 16, 2011
• Study Start: August 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: November 1, 2012
• Last Updated: March 9, 2017
• Results First Posted: January 16, 2017

Record last verified: 2017-01

Locations

ES (2); DE (5); US (2); NL (1); BE (2); PL (1)