E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Inoperable Locally Advanced or Metastatic Gastric Cancer that Responded to Platinum-based First-line Chemotherapy |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic Gastric Cancer |
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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 | 20.0 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of maintenance therapy with BGB-290 versus placebo in patients with inoperable locally advanced or metastatic gastric cancer with a complete response (CR) or confirmed partial response (PR) after first-line platinum-based chemotherapy, as measured by:
Progression-free survival (PFS) by Blinded Independent Review Committee (BIRC) assessment. |
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E.2.2 | Secondary objectives of the trial |
To further evaluate the efficacy of maintenance therapy with BGB-290 versus placebo in patients with inoperable locally advanced or metastatic gastric cancer with a CR or confirmed PR after first-line platinum-based chemotherapy, as measured by:
* Overall survival (OS)
* PFS by investigator assessment
* Progression-free survival 2 (PFS2) by investigator assessment
* Time to second subsequent treatment (TSST) by investigator assessment
* Objective response rate (ORR; CR or PR) by investigator assessment
* Duration of response by investigator assessment
* Time to response by investigator assessment
To evaluate safety and tolerability of BGB-290 versus placebo, as measured by:
* Incidence, timing, and severity of treatment-emergent adverse events (TEAEs), graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 or higher
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all of the following criteria to be eligible for the study:
1) Age 18 years
2) Histologically proven adenocarcinoma of the stomach or gastroesophageal junction, inoperable locally advanced or with metastatic disease
a) Patients with gastric cancer overexpressing HER2 are not allowed.
b) Irradiation as part of prior first-line treatment is not allowed.
3) Availability of archival tumor tissue for central laboratory determination of HRD status for randomization and exploratory biomarker analyses
4) Confirmed PR that is maintained for >=4 weeks or CR as determined by the investigator per RECIST Version 1.1
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E.4 | Principal exclusion criteria |
1) Unresolved acute effects of prior therapy of Grade ≥2
2) Prior treatment with a PARP inhibitor
3) Chemotherapy, biologic therapy, immunotherapy, investigational agent, anticancer Chinese medicine, or anticancer herbal remedies ≤14 days prior to randomization
4) Diagnosis of MDS
5) Leptomeningeal disease or brain metastasis
6) Previous complete gastric resection, chronic diarrhea, active inflammatory gastrointestinal disease, or any other disease causing malabsorption syndrome
7) Active bleeding disorder
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) assessed by Blinded Independent Review Committee (BIRC) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For PFS, there will be 1 planned interim analysis. The interim analysis will be performed when 242 PFS events (66.7% of the final target number of PFS events) have occurred at approximately 23 months after start of randomization, and the final analysis will be performed when 363 PFS events have occurred at approximately 29 months after start of randomization. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
There will be 1 interim analysis of OS at the final of PFS analysis. The interim analysis will be performed at the final PFS analysis with positive PFS results and expected 285 deaths. The final analysis will be performed when 390 deaths have occurred. |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 |
China |
France |
Germany |
Hong Kong |
Hungary |
Italy |
Japan |
Poland |
Russian Federation |
Singapore |
Spain |
Taiwan |
United Kingdom |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |