E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable, recurrent, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma |
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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 | 20.1 |
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 | 20.0 |
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 | 20.0 |
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 | 20.0 |
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 | 20.1 |
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 is to demonstrate superiority with regard to overall survival (OS) of avelumab plus best supportive care (BSC) versus physician’s choice (chosen from a pre-specified list of therapeutic options) plus BSC. |
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E.2.2 | Secondary objectives of the trial |
• To compare avelumab plus BSC versus physician’s choice plus BSC in regard to the following:
a.Progression-free survival based on an Independent Review Committee (IRC) assessment
b.ORR based on IRC assessment
c.Subject-reported outcomes/quality of life (QoL) using the European Quality of Life (EuroQOL) 5-dimensions and 5-levels questionnaire (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 ≥ 18 years
●Subjects with histologically confirmed unresectable, recurrent locally advanced or metastatic adenocarcinoma of the stomach or GEJ
●ECOG PS of 0 to 1 at trial entry
●Estimated life expectancy of more than 12 weeks
●Adequate hematological, hepatic and renal functions defined by the protocol
●Negative blood pregnancy test at Screening for women of childbearing potential.
●Highly 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
●Major surgery
●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
●Subjects will be excluded from the treatment with irinotecan or paclitaxel monotherapy if administration of their chemotherapy would be inconsisten with the current local labeling (for example, in regard to contraindications, warnings/precautions, or special provisions) for that chemotherapy. Investigators should check updated labeling via relevant websites before randomization.
●Subjects should start treatment administration within 28 days after signing the informed consent form (ICF). Treatment administration will start within 4 days after the randomization call.
●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 |
Analysis of the primary endpoint will occur after 256 events (deaths) have been observed and a minimum of 6 months follow-up since the last subject randomized. |
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E.5.2 | Secondary end point(s) |
1. Progression Free Survival (PFS)
2. Best Overall Response (BOR)
3. Change from baseline in European Quality Of Life 5-dimensions (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) Global Health Status
5. Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC STO22) Questionnaire Scores |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Analysis will occur after 256 events (deaths) have been observed and a minimum of 6 months follow-up since the last subject randomized. |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 |
Belgium |
Chile |
Colombia |
Czech Republic |
France |
Germany |
Hong Kong |
Italy |
Japan |
Korea, Republic of |
Poland |
Romania |
Russian Federation |
Spain |
Taiwan |
United States |
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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 trial is complete after the last subject comes off treatment and completes the safety follow-up. The sponsor may terminate the study at any time once access to study intervention of participants still benefitting is provisioned via a rollover study, expanded access, marketed product or another mechanism of access as appropriate. |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 3 |