E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced (unresectable, locally advanced or metastatic) adenocarcinoma of the stomach, or of the gastro-esophageal junction (GEJ) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066354 |
E.1.2 | Term | Adenocarcinoma of the gastroesophageal junction |
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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071114 |
E.1.2 | Term | Metastatic gastric adenocarcinoma |
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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063916 |
E.1.2 | Term | Metastatic gastric cancer |
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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017761 |
E.1.2 | Term | Gastric cancer recurrent |
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 |
The primary objective of this trial is to demonstrate superiority of maintenance therapy with avelumab versus continuation of first-line chemotherapy with regard to OS in subjects who have not progressed on first-line chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
• To demonstrate superiority of maintenance therapy with avelumab versus continuation of first-line chemotherapy with regard to PFS as per RECIST v1.1
• To demonstrate superiority of maintenance therapy with avelumab versus continuation of first-line chemotherapy with regard to the objective response rate (ORR) as per RECIST v1.1
• To compare the subject-reported outcomes / quality of life of subjects when treated with avelumab versus continuation of first-line chemotherapy as assessed by the European Quality of Life (EuroQOL) EQ-5D-5L, and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and module QLQ-STO22
• To determine the safety and tolerability of avelumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
●Male or female subjects aged greater than or equal to (>=) 18 years
●Disease must be measurable by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
●Subjects with histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
●Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry
●Estimated life expectancy of more than 12 weeks
●Adequate haematological, hepatic and renal functions defined by the protocol
●Negative blood pregnancy test at Screening for women of childbearing potential
●Effective contraception for both male and female subjects if the risk of conception exists
●Other protocol defined criteria could apply |
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E.4 | Principal exclusion criteria |
●Prior therapy with any antibody or drug targeting T-cell coregulatory proteins
●Concurrent anticancer treatment
●Prior chemotherapy for unresectable locally advanced or metastatic adenocarcinoma of the stomach or GEJ
●Tumor shown to be HER2 possitive
●Major surgery for any reason, except diagnostic biopsy, within 4 weeks of enrolment and/or if the subject has not fully recovered from the surgery within 4 weeks of enrolment
●Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to < 10 mg prednisone daily).
●All subjects with brain metastases, except those meeting the following criteria: a. Brain metastases have been treated locally, and b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
●Previous malignant disease (other than gastric cancer) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ (bladder,
cervical, colorectal, breast)
●Prior organ transplantation, including allogeneic stem-cell transplantation
●Significant acute or chronic infections
●Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
●Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
●Persisting toxicity related to prior therapy except alopecia
●Neuropathy Grade > 3.
●Pregnancy or lactation
●Known alcohol or drug abuse
●History of uncontrolled intercurrent illness including hypertension, active infection, diabetes
●Clinically significant (i.e., active) cardiovascular disease
●All other significant diseases might impair the subject’s tolerance of trial treatment
●Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with study requirements
●Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
●Legal incapacity or limited legal capacity
●Other protocol defined criteria could apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time (in months) from randomization to the date of death, regardless of the actual cause of the subject’s death. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints:
1. Progression-free Survival
2. Best Overall Response
3. Change from baseline in European Quality Of Life 5-dimensions-5 levels (EQ-5D-5L) Health Outcome Questionnaire 4. Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30)
5. Change from baseline in European Organization for Research and Treatment of Cancer Gastric Cancer Module QLQ-STO22 6. Number of subjects with Treatment-Emergent Adverse Events (TEAEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PFS, BOR: From the date of randomization up to 3 years
Quality of life endpoints: Week 4, 7, 13 and then every 6 weeks until 12 weeks after last treatment, assessed up to 3 years Safety: From the first dose of study drug administration up to 28 days after the last dose of study drug administration |
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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 | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 90 |
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 |
Australia |
Brazil |
Canada |
Japan |
Korea, Republic of |
Taiwan |
Thailand |
United States |
France |
Romania |
Spain |
Germany |
Italy |
Hungary |
Russian Federation |
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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The survival follow-up will continue until 5 years after the last subject receives the last dose of avelumab.
Expected date for the primary endpoint is 25Nov2018 and the completion expected date is 25Nov2023. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 10 |