E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unrespectable locally advanced or metastatic gastric or esophagogastric unction adenocarcinoma |
|
E.1.1.1 | Medical condition in easily understood language |
Gastric and esophageal Cancer |
|
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 | 14.1 |
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) |
|
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 |
Primary
Part 1 (phase 1b-open label):
• To identify safe dose levels of AMG 102, up to 15 mg/kg Q3W, to combine with
ECX.
Part 2 (phase 2-double-blind):
• To estimate with pre-specified precision the effect of the addition of AMG 102 to
ECX on the progression free survival (PFS) of previously untreated subjects with
unresectable locally advanced or metastatic gastric or esophagogastric junction
adenocarcinoma. |
|
E.2.2 | Secondary objectives of the trial |
Secondary
Part 1
To evaluate the incidence of adverse events, abnormal laboratory values not defined as DLTs, and anti-AMG 102 antibody formation.
To evaluate the PK of AMG 102 (Cmax and Cmin).
Part 2
To evaluate the effect of the addition of AMG 102 to ECX on OS, response rates, time to response, duration of response, disease control rates, incidence of adverse events and laboratory abnormalities.
To evaluate the PK (Cmax and Cmin) of AMG 102, and estimate the impact of
co-administration of AMG 102 to the PK of epirubicin and cisplatin in a sub-group of
subjects at selected sites outside of Europe/Asia. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria
4.1.1 Disease related
• Pathologically confirmed unresectable locally advanced or metastatic gastric or
esophagogastric junction (EGJ) adenocarcinoma; tumors of the distal esophagus
within 5 cm of the EGJ are eligible
• ECOG performance status 0 or 1
• Life expectancy ≥ 3 months
4.1.2 Demographic
• Male or female ≥ 18 years of age
4.1.3 Ethical
• Before any study-specific procedure, the appropriate written informed consent
must be obtained (see Section 12.1)
4.1.4 Laboratory
• Hemoglobin ≥ 9 g/dL (can be post-transfusion)
• Absolute neutrophil count ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L (without transfusion within 14 days before enrollment
or randomization)
• Creatinine clearance ≥ 60 mL/minute (calculated or measured)
• Aspartate aminotransferase (AST) and alanine amino transferase (ALT) ≤ 2.5 x
ULN (OR AST and ALT ≤ 5.0 x ULN in the presence of liver metastasis)
• Total bilirubin ≤ 1.5x ULN
• Partial thromboplastin time (PTT) ≤ 1.5 x ULN and international normalized ratio
(INR) ≤ ULN
4.1.5 General
• Plan to begin protocol specific therapy within 7 days after enrollment or
randomization
• Able to tolerate infusions and take oral medications |
|
E.4 | Principal exclusion criteria |
Exclusion Criteria
4.2.1 Disease Related
• Previous systemic therapy (chemotherapy or biologic therapy) for locally
advanced or metastatic gastric or esophagogastric adenocarcinoma
• Less than 6 months have elapsed from completion of prior neoadjuvant or
adjuvant chemotherapy or chemoradiotherapy. Patients previously treated with
anthracyclines must not exceed total cumulative dose of epirubicin of 900 mg/m2
(or equivalent thereof, if a different anthracycline has been administered in the
past) including doses to be administered in this trial.
• Any prior or synchronous malignancy (except for non-melanomatous skin cancer
or in situ cervical cancer) other than the study disease, unless treated with
curative intent and having completed all therapy with no evidence of disease ≤ 5
years before enrollment or randomization
• Known peripheral neuropathy > grade 1
• Known dihydropyrimidine dehydrogenase deficiency (DPD)
• Any clinically significant medical condition other than cancer, including
cardiovascular disease or chronic obstructive pulmonary disease (COPD), which
in the opinion of the investigator would interfere with the safe delivery of study
treatment or increase risk of toxicity
• History of any medical condition that in the opinion of the investigator, may
increase the risks associated with study participation or study treatments or may
interfere with the conduct of the study or interpretation of study results
• Major surgical procedure ≤ 30 days before enrollment or randomization or not yet
recovered from prior major surgery
• Minor surgery (e,g. catheter or gastrostomy tube placement) ≤14 days before
enrollment or randomization or not yet recovered from prior minor surgery;
although placement of central venous access device, fine needle aspiration,
thoracentesis, endoscopic biliary stent or paracentesis ≥ 1 day before enrollment
or randomization is acceptable
• Subjects with resectable disease or suitable for definitive chemoradiation
• Plans for surgical resection based on response to protocol therapy
• Subjects who have persistent gastric outlet obstruction, complete dysphagia or
are dependent upon jejunostomy for feeding.
• Tumors of squamous cell histology
• Treatment with radiotherapy ≤ 14 days before enrollment or randomization
• Known central nervous system metastases
• Clinically significant upper gastro-intestinal bleeding < 30 days prior to enrollment
or randomization
4.2.2 Cardiac
• LVEF < 50% as determined by either MUGA scan or ECHO
• Clinically significant (i.e. active) cardiac disease or myocardial infarction within
the last 12 months before enrollment or randomization. Patients with any history
of clinically significant cardiac failure are excluded from study entry
4.2.3 Other abnormal medical conditions
• Serious or non-healing wound
• Known positive test for HIV, hepatitis C, chronic or active hepatitis B
• Presence of peripheral edema > Grade 2
• Thrombosis or vascular ischemic events within the last twelve months, such as deep venous thrombosis, pulmonary embolism, transient ischemic attack, cerebral infarction, or myocardial infarction.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoints:
Part 1
• The incidence of adverse events defined as DLTs
Part 2
• PFS
Secondary Endpoints:
Part 1
• Incidence of adverse events, abnormal laboratory values not defined as DLTs, and anti- AMG 102 antibody
• Cmax and Cmin of AMG 102 concentration
Part 2
• OS
• Objective response rate (complete and partial response), disease control rate, duration of
response, and time to response
• The incidence of adverse events, laboratory abnormalities, and anti-AMG102 antibody
formation.
• Cmax and Cmin of AMG 102; Cmax and AUC of epirubicin, and cisplatin when used with or without AMG 102 in a sub-group of subjects at selected sites outside of Europe/Asia. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The date when all subjects have died, completed the treatment period, or long-term follow-up (until 36 months from the date that the last subject was randomized), whichever is later. |
|
E.5.2 | Secondary end point(s) |
Secondary Endpoints:
Part 1
• Incidence of adverse events, abnormal laboratory values not defined as DLTs, and anti- AMG 102 antibody
• Cmax and Cmin of AMG 102 concentration
Part 2
• OS
• Objective response rate (complete and partial response), disease control rate, duration of
response, and time to response
• The incidence of adverse events, laboratory abnormalities, and anti-AMG102 antibody
formation.
• Cmax and Cmin of AMG 102; Cmax and AUC of epirubicin, and cisplatin when used with or without AMG 102 in a sub-group of subjects at selected sites outside of Europe/Asia. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The date when all subjects have died, completed the treatment period, or long-term follow-up (until 36 months from the date that the last subject was randomized), whichever is later. |
|
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Canada |
Hong Kong |
India |
Russian Federation |
Singapore |
|
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
|
The end of study will occur when all subjects have died, completed the treatment period or long-term follow-up (for a maximum of 36 months from the date that the last subject was enrolled or randomized) whichever is later. The end of study for each subject is defined as the date the subject withdraws consent from the study, completes the final long-term follow-up visit, or death, whichever is earlier. |
|
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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |