A Study of Ramucirumab Combination Therapy in Japanese Participants Who Have Advanced Stomach Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and antitumor response of ramucirumab in combination with platinum/fluoropyrimidine regimens in Japanese participants with advanced gastric/gastrooesophageal junction cancer who have not received chemotherapy.

Official Title
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Phase 1b Study of Ramucirumab in Combination With Fluoropyrimidines and Platinum-Based Agents in Japanese Patients With Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma

Conditions
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Stomach Neoplasms

Intervention / Treatment
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* Drug: Ramucirumab
* Drug: Capecitabine
* Drug: Cisplatin
* Drug: S-1
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma which is metastatic or locally advanced and unresectable. A participant with esophageal cancer is not eligible. Not have received prior first-line systemic chemotherapy for locally advanced and unresectable and/or metastatic disease. Participants whose disease has progressed after >6 months following the last dose of systemic treatment in the adjuvant/neoadjuvant setting are eligible. Measurable or nonmeasurable, but evaluable, disease, determined using guidelines in Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at the time of enrollment. The participant has adequate organ function. Resolution to Grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version [v]4.03) of all clinically significant toxic effects of prior locoregional therapy, surgery, or other anticancer. Female participants of childbearing potential must have a negative serum or urinary pregnancy. Have an estimated life expectancy of ≥12 weeks in the judgment of the investigator. Exclusion Criteria: A significant bleeding disorder, vasculitis, or had a significant bleeding episode from the gastrointestinal tract within 12 weeks prior to enrollment. Uncontrolled arterial hypertension, despite standard medical management. A serious or nonhealing wound or peptic ulcer or bone fracture at enrollment. Undergone major surgery within 28 days prior to enrollment, or subcutaneous venous access device (reservoir) placement within 7 days prior to enrollment. Radiation therapy within 14 days prior to enrollment. Received any previous systemic therapy (including investigational agents) targeting vascular endothelial growth factor (VEGF) or the VEGF receptor signaling pathways. Cirrhosis at a level of Child-Pugh B (or worse); or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. A serious illness or medical condition(s). Pregnant or breastfeeding. Dysphagia for oral medication. Known allergy or hypersensitivity to any study treatment. Human epidermal growth factor receptor (HER) 2 status of positive. Received treatment within 28 days of the initial dose of study drug with an investigational product or non-approved use of a drug or device.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Ramucirumab + Capecitabine + Cisplatin<br>Ramucirumab (8 milligram per kilogram (mg/kg) given intravenously (IV) on days 1 and 8 in combination with 1000 mg/square meter (m^2) capecitabine given orally twice a day on days 1 through 14 and 80 mg/m^2 cisplatin given IV on day 1 of each 21 day cycle (up to 6 cycles). Participants may continue to receive treatment until discontinuation criteria are met. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: IMC-1121B;Drug: Capecitabine<br>* Administered orally<br>Drug: Cisplatin<br>* Administered IV<br>|
| Other: Ramucirumab + S-1 + Cisplatin<br>Ramucirumab 8 mg/kg given IV on days 1 and 8 of 21 day in combination with 40 mg/m^2 tegafur/gimeracil/oteracil (S-1) given orally twice a day on days 1 through 21 and 60 mg/m^2 cisplatin given IV on day 8 of each 35 day cycle (up to 8 cycles). Participants may continue to receive treatment until discontinuation criteria are met. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: IMC-1121B;Drug: Cisplatin<br>* Administered IV<br>Drug: S-1<br>* Administered orally<br>|
| Other: Ramucirumab + S-1 + Oxaliplatin<br>Ramucirumab 8 mg/kg given IV on days 1 and 8 in combination with 40 mg/m^2 S-1 given orally twice a day on days 1 through 14 and 100 mg/m^2 oxaliplatin given IV on day 1 of each 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: IMC-1121B;Drug: S-1<br>* Administered orally<br>Drug: Oxaliplatin<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | Clinically significant events were defined as serious adverse events (SAE). A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. | First Dose to Study Completion Plus 30-Day Safety Follow-Up (Up To 22 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Ramucirumab | Maximum Serum Concentration (Cmax) of Ramucirumab. | Day 1, Day 8, Day 43, Day 50, Day 85 and Day 92: End of Infusion | 
| Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) of Ramucirumab | Minimum Serum Concentration (Cmin) of Ramucirumab. | Day 8, Day 22, Day 29, Day 43, Day 50, Day 64, Day 71, Day 85, Day 92 and Day 106: Pre-Dose | 
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate) | Objective response rate (ORR) was defined as the percentage of randomized participants achieving a best confirmed overall response of CR or PR using Response Evaluation Criteria in Solid Tumors (RECIST v1). CR was defined as the disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions, taking as reference the baseline sum LD and no progression in non-target lesions. | First Dose to Date of Objective Progressive Disease or Death Due to Any Cause (Up To 22 Months) | 
| Number of Participants With Treatment Emergent Anti-Ramucirumab Antibodies (TE-ADA) | Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. | First dose to study completion plus 30-day safety follow-up (Up To 22 Months) |