E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Gastric, Gastroesophageal Junction, or Distal Esophageal 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 | 14.0 |
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 | 14.0 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To estimate the treatment effect as measured by progression free survival (PFS) of subjects receiving AMG 386 (at 2 doses) in combination with CX relative to CX/placebo |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of the combination regimen of AMG 386 with CX
- To estimate other measures of treatment effect (objective response rate, duration of response, overall survival, time to progression and time to response)
- To evaluate the pharmacokinetics of AMG 386 when used in combination with CX
- To estimate the immunogenicity as assessed by the incidence of anti-AMG 386 antibody formation
- To estimate the impact of AMG 386 on cancer-related symptoms based on patient reported outcomes using the QLQ-STO22 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
A pharmacokinetics substudy for cisplatin and capecitabine is described in the protocol. No subjects from the EU will be enrolled in this substudy. |
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E.3 | Principal inclusion criteria |
Disease Related:
- Histologically or cytologically confirmed adenocarcinoma of the stomach, gastroesophageal junction or distal esophagus with metastatic disease
- Measurable or non-measurable disease per RECIST Guidelines
- Prior gastrectomy (total or partial) may be allowed as long as subjects can take oral medications and meet all other inclusion/exclusion criteria. Subjects may not take crushed or dissolved capecitabine via a feeding/gastrostomy tube
- Palliative radiotherapy for metastatic esophageal or gastric cancer prior to study entry may be allowed as long as all toxicities from radiotherapy have resolved and the radiotherapy was not to the only site of known metastatic disease
Demographic:
-18 years of age or older at the time the written informed consent is obtained
General
- Able to swallow oral medication
- ECOG performance status of 0 or 1
Laboratory
- Adequate organ and hematological function as evidenced by laboratory studies prior to randomization
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E.4 | Principal exclusion criteria |
Disease Related:
- Prior chemotherapy for metastatic disease (1st line)
- Less than 12 months have elapsed from completion of previous adjuvant or neoadjuvant chemotherapy or chemoradiotherapy
- Subjects with persistent gastric outlet obstruction, complete dysphagia or feeding jejunostomy
- Radiotherapy ≤ 14 days prior to randomization. Subjects must have recovered from all radiotherapy-related toxicities
- Current or prior history of central nervous system metastases
- History of arterial or deep venous thromboembolism within 12 months prior to randomization
- History of bleeding diathesis or clinically significant bleeding within 6 months prior to randomization
- Major surgical procedure within 28 days prior to randomization
- Minor surgical procedure, placement of central venous access device or fine needle aspiration within 3 days prior to randomization
- Prior malignancy except: malignancy treated with curative intent and without evidence of active disease for ≥ 3 years prior to randomization and felt to be at low risk for recurrence by treating physician, adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease, adequately treated cervical carcinoma in situ without evidence of disease, prostatic intraepithelial neoplasia without evidence of prostate cancer
- Prior malignancy (other than in situ cervical cancer, or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for ≥ 3 years prior to randomization
- Clinically significant cardiovascular diseases within 12 months prior to randomization
- Presence of clinically significant non-healing wound, ulcer (including gastrointestinal) or fracture as judged by the investigator
- Ongoing or clinically significant active infection as judged by the investigator
- Known hypersensitivity to bacterial proteins, or any of the drugs required in this study
- Known peripheral neuropathy ≥Grade 1
- Known dihydropyrimidine dehydrogenase deficiency
- Known hypersensitivity to 5-FU/capecitabine
- Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen
- Known active or chronic hepatitis
Medications:
- Currently or previously treated with angiopoietin inhibitors, or inhibitors of TIE-1 or TIE-2
- Treatment with immune modulators such as cyclosporine or tacrolimus within 30 days prior to randomization
- Treatment with sorivudine or its chemically related analogues
- Anticoagulants (other than aspirin and anti-platelet agents) within 7 days prior to randomization. The concurrent use of low molecular weight heparin or heparanoids or low dose warfarin (i.e, ≤ 1 mg daily) for prophylaxis against thrombosis is acceptable while on study
General:
- Not yet completed at least 30 days since ending other investigational device/drug trial(s), or subject is receiving other investigational treatments
- Pregnant or is breast feeding
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
When 113 subjects have experienced a PFS event |
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E.5.2 | Secondary end point(s) |
Safety and Tolerability
Objective Response Rate (ORR)
Duration of Response (DOR)
Overall Survival (OS)
Time to Progression (TTP)
Time to Response
Pharmacokinetics
Patient Reported Outcomes |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
When 113 subjects have experienced a PFS event |
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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 | No |
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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) | 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 | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Austria |
Belgium |
France |
Hungary |
Netherlands |
Poland |
Spain |
United Kingdom |
United States |
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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
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The end of study is when all subjects have completed the treatment period or long-term follow-up (maximum 48 months from the date the last subject is randomized), whichever is later. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |