E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced adenocarcinoma of the stomach or the lower esophagus |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001150 |
E.1.2 | Term | Adenocarcinoma gastric |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001173 |
E.1.2 | Term | Adenocarcinoma of esophagus |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- Determine antitumoral activity of IMAB362 as monotherapy in patients with metastatic, refactory or recurrent disease of advanced adenocarcinoma of the stomach or the lower esophagus proven by histology |
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E.2.2 | Secondary objectives of the trial |
- Determine profile of adverse effects, safety and tolerability of repeated application
- Determine pharmacokinetics and immunogenicity after repeat dosing |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Metastatic, refractory or recurrent disease of advanced adenocarcinoma of the stomach or the lower esophagus proven by histology,
- CLDN18.2 expression confirmed by immunohistochemistry in paraffin embedded tumor tissue sample in at least 50 % of the tumor cells with a staining of at least 2+ (on a scale from 0 to +3)
- At least 1 measureable site of disease according to RECIST criteria (CT scans or MRI not older than 2 weeks before visit 2),
- Age ≥ 18 years,
- Written Informed consent,
- ECOG performance status (PS) 0-1 or Karnofsky INdex 70-100%
- Life expectancy > 3 months,
- Platelet count ≥ 100,000/mm³,
- Hemoglobin ≥ 10 g/dl,
- Bilirubin normal,
- AST and ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present),
- Creatinine < 1.5 x ULN,
- For women eith childbearing potential (last menstruation less than 2 years prior to enrolment): Negative pregnancy test (β-HCG) at baseline and using two highly effective methods of contraception during the treatment phase and for 8 weeks after the last infusion of the study drug,
- Male patients whose sexual partners are women of child bearing potential must use an accepted contraceptive method during the treatment phase and for 8 weeks after the last infusion of the study drug. |
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E.4 | Principal exclusion criteria |
Patients meeting any one or more of the following exclusion criteria are not eligible for study entry:
- Pregnancy or breastfeeding,
- Prior severe allergic reaction or intolerance to a monoclonal antibody, including humanized or chimeric antibodies,
- Less than 3 weeks sinde prior chemo- or radiation therapy,
- Other investigational agents or devices concurrently or within 4 weeks prior to this study,
- Other concurrent anticancer therapies (not for the indication under study treatment),
- known HIV infection or known active hepatitis (A, B, C),
- Concurrent anticoagulation with vitamin K antagonists (e. g. Coumadin, Marcumar),
- Therapeutic doses of heparin (prophylactic doses are accepted),
- Uncontrolled illness including, but nor limited to, any of the following:
-- Ongoing or active infection requiring parenteral antibiotics
-- Symptomatic congestive heart failure
-- Unstable angina pectoris
-- Uncontrolled hypertension
-- Clinically significant cardiac arrhytmia
-- Myocardial infarction within the past 6 months
-- Gastric bleeding within last four weeks
-- Symptomatic peptic ulcer
-- Clinical symptoms of cerebral metastasis
- Psychiatric illness or social situations that would preclude study compliance |
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of remission (CR, PR) (RECIST Criteria),
Evaluation of antitumoral activity by CT or MRI before start of therapy and at visit 9 and visit 10.
Patients receiving continued treatment will be evaluated by CT or MRI in 8-12 weeks intervals until 6 month after last infusion.
All patients will be additionally evaluated by CT or MRI at visit 11 and visit 12. |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 |
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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 | Information not present in EudraCT |
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 | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
Austria |
Bulgaria |
Czech Republic |
Germany |
Latvia |
Lithuania |
Poland |
Switzerland |
Turkey |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 17 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 17 |
E.8.9.2 | In all countries concerned by the trial days | 0 |