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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01316263
First received: March 14, 2011
Last updated: November 18, 2016
Last verified: November 2016

March 14, 2011
November 18, 2016
August 2011
May 2012   (Final data collection date for primary outcome measure)
Percentage of Participants With Tumor Response of Stable Disease (SD), Partial Response (PR) or Complete Response (CR) (Clinical Benefit Rate) at 12 Weeks [ Time Frame: 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.
Tumor response of Stable Disease (SD) or better at 12 weeks [ Time Frame: 12 weeks ]
Complete list of historical versions of study NCT01316263 on ClinicalTrials.gov Archive Site
  • Progression-Free Survival (PFS) [ Time Frame: Baseline to the first date of objectively determined PD or death from any cause up to 35.9 weeks ]
    PFS defined as the duration from date of first dose of study drug until first radiographic documentation of PD using RECIST, v1.1 criteria or death from any cause. PD defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 mm and the appearance of ≥1 new lesions was progression. Participants who died with no prior PD were considered to have progressed on day of death. Participants who did not progress or were lost to follow-up were censored at date of last radiographic tumor assessment; if no assessment was available censoring was at date of registration. If death or PD occurred after 2 consecutive missing radiographic visits censoring was date of last radiographic visit prior to missed visits. Use of new anticancer therapy prior to PD, censoring was date of last radiographic assessment prior to new therapy.
  • Percentage of Participants With CR or PR [Radiographic Objective Response Rate (ORR)] [ Time Frame: Baseline up to 35.9 weeks and post study discontinuation 30-day follow-up ]
    The ORR was the best overall response of CR and PR using RECIST, v1.1 criteria. Participants who did not have a tumor response assessment for any reason were considered nonresponders and were included in the denominator that calculated the response rate. Percentage of participants = (number of participants achieving a response/total of participants treated) * 100.
  • Overall Survival (OS) [ Time Frame: Date of first dose of study drug to the date of death from any cause up to 57.3 weeks ]
    OS was defined as the time from the date of first dose of study drug to the date of death from any cause. Participants who were alive at the end of the post-study follow-up or were lost to follow-up were censored on the last date the participant was known to be alive.
  • Number of Participants With Adverse Events (AE) and Participants Who Died [ Time Frame: Baseline up to 57.3 weeks and 30-day post study-discontinuation follow-up ]
    Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs, regardless of causality. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. The number of participants who died due to an AE or disease progression are also reported.
  • Percentage of Participants With CR, PR or SD [Disease Control Rate (DCR)] [ Time Frame: Baseline up to 35.9 weeks ]
    DCR defined as CR, PR or SD using RECIST v1.1 criteria. CR was defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 mm. PR was defined as ≥30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify PD, taking as reference the smallest sum diameter since the treatment started. PD defined as ≥20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Sum must also have demonstrated an absolute increase of ≥5 mm, or the appearance of 1 or more new lesions was considered progression. Percentage of participants=(number of participants with CR+PR+SD/number of participants in group) * 100.
  • Maximum Concentration (Cmax) [ Time Frame: Day 1 of Cycles 1 and 3 (14-day cycles) ]
  • Area Under the Curve (AUC) [ Time Frame: Day 1 of Cycles 1 and 3 (14-day cycles) ]
  • Half Life (t½) [ Time Frame: Day 1 of Cycles 1 and 3 (14-day cycles) ]
  • Clearance (CL) [ Time Frame: Day 1 of Cycles 1 and 3 (14-day cycles) ]
  • Volume of Distribution at Steady State (Vss) [ Time Frame: Day 1 of Cycles 1 and 3 (14-day cycles) ]
  • Percentage of Participants With Human Anti-Olaratumab (IMC-3G3) Antibody Results [ Time Frame: Day 1 of Cycles 1, 3, 6, 12 and 18 prior to infusion (14-day cycles) ]
    Participants with Treatment Emergent (TE) anti-olaratumab (IMC-3G3) antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.
  • Progression-Free Survival (PFS) [ Time Frame: From enrollment to the first date of objectively determined progressive disease or death from any cause (tumor assessments performed every 6 weeks ) ]
  • Radiographic Objective Response Rate (ORR) [ Time Frame: Approximately 15 Months ]
  • Overall Survival (OS) [ Time Frame: Date of first dose of study therapy to the date of death from any cause ]
  • Summary listing of participants with Adverse Events [ Time Frame: Approximately 15 Months ]
  • Maximum Concentration (Cmax) [ Time Frame: Day 1 of Cycle 1, 3, 6, 12 and 18 ]
  • Area Under the Curve (AUC) [ Time Frame: Day 1 of Cycle 1, 3, 6, 12 and 18 ]
  • Half Life (t 1/2) [ Time Frame: Day 1 of Cycle 1, 3, 6, 12 and 18 ]
  • Clearance (CL) [ Time Frame: Day 1 of Cycle 1, 3, 6, 12 and 18 ]
  • Volume of Distribution at Steady State (Vss) [ Time Frame: Day 1 of Cycle 1, 3, 6, 12 and 18 ]
  • Anti-IMC-3G3 Antibody assessment [ Time Frame: Prior to infusion on Day 1 of Cycle 1, 3, 6, 12 and 18 ]
  • Disease Control Rate (DCR) [ Time Frame: Approximately 15 Months ]
    determined by the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)
Not Provided
Not Provided
 
A Study of Olaratumab (IMC-3G3) in Previously Treated Participants With Unresectable and/or Metastatic Gastrointestinal Stromal Tumors
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)
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.
Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Gastrointestinal Stromal Tumor (GIST)
Biological: Olaratumab
Administered IV
Other Names:
  • LY3012207
  • IMC-3G3
  • Experimental: PDGFRα mutation negative
    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.
    Intervention: Biological: Olaratumab
  • Experimental: PDGFRα mutation positive
    Participants with GIST with genotypes that have a PDGFRα mutation given 20 mg/kg Olaratumab IV every 14 days.
    Intervention: Biological: Olaratumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
November 2012
May 2012   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium,   Germany,   Netherlands,   Poland,   Spain
Italy
 
NCT01316263
14244, CP15-1008, I5B-IE-JGDH, 2010-022560-12
No
Not Provided
Not Provided
Not Provided
Eli Lilly and Company
Eli Lilly and Company
Not Provided
Study Director: 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
Eli Lilly and Company
November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP