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

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Primary Purpose

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Olaratumab

About this trial

This is an interventional treatment trial for Gastrointestinal Stromal Tumor (GIST)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

PDGFRα mutation negative

PDGFRα mutation positive

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Progression-Free Survival (PFS)

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)]

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)

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

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)]

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)

Area Under the Curve (AUC)

Half Life (t½)

Clearance (CL)

Volume of Distribution at Steady State (Vss)

Percentage of Participants With Human Anti-Olaratumab (IMC-3G3) Antibody Results

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.

Full Information

NCT ID

NCT01316263

First Posted

March 14, 2011

Last Updated

January 27, 2017

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT01316263

Brief Title

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

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Terminated

Why Stopped

Trial terminated strategically due to poor accrual.

Study Start Date

August 2011 (undefined)

Primary Completion Date

May 2012 (Actual)

Study Completion Date

November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastrointestinal Stromal Tumor (GIST)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PDGFRα mutation negative

Arm Type

Experimental

Arm Description

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.

Arm Title

PDGFRα mutation positive

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

Olaratumab

Other Intervention Name(s)

LY3012207, IMC-3G3

Intervention Description

Administered IV

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Progression-Free Survival (PFS)

Description

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.

Time Frame

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

Title

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

Description

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.

Time Frame

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

Title

Overall Survival (OS)

Description

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.

Time Frame

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

Title

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

Description

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.

Time Frame

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

Title

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

Description

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.

Time Frame

Baseline up to 35.9 weeks

Title

Maximum Concentration (Cmax)

Time Frame