E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastrointestinal Stromal Tumors (GIST) |
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E.1.1.1 | Medical condition in easily understood language |
Cancer of the connective tissue of the digestive tract |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051066 |
E.1.2 | Term | Gastrointestinal stromal tumour |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the tumor response of stable disease, partial response, or complete response at 12 weeks (according to RECIST 1.1 criteria) in two separate cohorts representing molecularly distinct subsets of previously treated patients with GIST when treated with IMC-3G3: Cohort 1 includes patients with GIST harboring PDGFRα mutations (D842V and any others), while Cohort 2 includes patients with GIST not harboring PDGFRα mutations. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the progression-free survival;
• To evaluate the safety profile of IMC-3G3 in patients with GIST;
• To evaluate the radiographic objective response rate (ORR) and disease control rate (DCR) determined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1);
• To evaluate the OS; and
• To evaluate the PK profile and immunogenicity of IMC-3G3. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
● Patient has histologically or cytologically confirmed, unresectable and/or metastatic GIST.
● Patient has measurable disease.
● Patient has documented objective progression following, or intolerance to, treatment with both imatinib and
sunitinib.
● Patient's Eastern Cooperative Oncology Group (ECOG) performance status is 0 to 2.
● Patient has either:
1. prior results from 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.
● Patient 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.
● Patient has a life expectancy of ≥ 3 months. |
|
E.4 | Principal exclusion criteria |
● Patient has untreated central nervous system metastases, and as a result, is clinically unstable
with regard to neurologic function.
● Patient has a history of another primary cancer.
● Patient has received any investigational therapy within 14 days prior to registration.
● Patient is receiving concurrent treatment with other anticancer therapy.
● Patient has known immunodeficiency virus (HIV) infection.
● Patient has undergone major surgery within 28 days prior to registration.
● If female, patient is pregnant or breastfeeding. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is tumor response rate of SD or better at 12 weeks. The tumor response rate of SD or better at 12 weeks is defined as the proportion of patients with a response of SD or better, as defined by RECIST 1.1, at 12 weeks following the first dose of study therapy. Patients will be considered “failure” if they die or if radiographic evaluation indicates a response of PD at 12 weeks or before. The tumor response rate of SD or better at 12 weeks and its 90% confidence limit will be estimated. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks following the first dose of study therapy |
|
E.5.2 | Secondary end point(s) |
Secondary Efficacy endpoints include PFS, OS and ORR.
PFS is defined as the time from first dose of study therapy until the first radiographic documentation of disease progression per RECIST 1.1, or death from any cause.
Overall survival is defined as the time from the date of first dose of study therapy to the date of death from any cause.
The ORR is equal to the proportion of patients achieving a best overall response of partial or complete response (PR + CR), according to RECIST 1.1. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity Assessments |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Simon Two-Stage Optimal Design |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The study will be considered closed when all patients have progressed, died, or completed study therapy and been followed for at least 30 days from last dose. In addition, before the study will be considered closed, the investigator remains responsible for following, through an appropriate health care option, AEs that are serious or that caused the patient to discontinue before completing the study. The patient should be followed until the event is resolved or explained. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |