Unrespectable locally advanced or metastatic gastric or esophagogastric unction adenocarcinoma MedDRA version: 14.1 Level: LLT Classification code 10017759 Term: Gastric cancer in situ System Organ Class: 100000004864
Conditions
Interventions
Product Name: AMG 102
Product Code: AMG 102
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AMG 102
Conc
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 82 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 39
Exclusion criteria
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 co
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Part 1 - throughout Paty 1 Part 2 - time from start of study until progression ; Main Objective: 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. ; Secondary Objective: 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. ; Primary end point(s): Primary Endpoints: Part 1 • The incidence of adverse events defined as DLTs Part 2 • PFS Secondary Endpoints: | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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 (CR and PR per RECIST with modifications) , disease control rate (CR, PR and SD per RECIST with modifications), time to response (for responders only), and duration of response (for responders only) • Incidence of adverse events, significant laboratory value changes from baseline and anti-AMG 102 antibody formation • Cmax and Cmin for AMG 102; Cmax and AUC for epirubicin and cisplatin when used with or without AMG 102 in a sub-group of subjects at selected sites outside of Europe/Asia ; Timepoint(s) of evaluation of this end point: PFS: time from randomization to disease progression, symptomatic deterioration, or death. OS: time from randomization to death. Objective Response Rate: the proportion of subjects (with measurable disease at baseline) who have either confirmed complete response (CR) or confirmed partial response (PR) Disease Control Rate: the proportion of subjects with measurable disease at baseline who have either complete response (CR), partial response (PR), or stable disease (SD) per RECIST with modifications. Time to response: time from randomization to date of first response. Duration of Response: time from first objective response to first disease progression or death due to progressive disease. | — |
Countries
Australia, Belgium, Canada, Greece, Hungary, India, Italy, Poland, Russian Federation, Singapore, Spain, United Kingdom, United States
Contacts
Public ContactIHQ Medical Info – Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed