Phase 1b Study of Ramucirumab in Combination With Fluoropyrimidines and Platinum-Based Agents in Japanese Patients With Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma
Overview
- Phase
- Phase 1
- Intervention
- Ramucirumab
- Conditions
- Stomach Neoplasms
- Sponsor
- Eli Lilly and Company
- Enrollment
- 18
- Locations
- 2
- Primary Endpoint
- Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
- •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.
Arms & Interventions
Ramucirumab + Capecitabine + Cisplatin
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.
Intervention: Ramucirumab
Ramucirumab + Capecitabine + Cisplatin
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.
Intervention: Capecitabine
Ramucirumab + Capecitabine + Cisplatin
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.
Intervention: Cisplatin
Ramucirumab + S-1 + Cisplatin
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.
Intervention: Ramucirumab
Ramucirumab + S-1 + Cisplatin
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.
Intervention: Cisplatin
Ramucirumab + S-1 + Cisplatin
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.
Intervention: S-1
Ramucirumab + S-1 + Oxaliplatin
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.
Intervention: Ramucirumab
Ramucirumab + S-1 + Oxaliplatin
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.
Intervention: S-1
Ramucirumab + S-1 + Oxaliplatin
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.
Intervention: Oxaliplatin
Outcomes
Primary Outcomes
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Time Frame: First Dose to Study Completion Plus 30-Day Safety Follow-Up (Up To 22 Months)
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.
Secondary Outcomes
- Pharmacokinetics (PK): 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)(First Dose to Date of Objective Progressive Disease or Death Due to Any Cause (Up To 22 Months))
- Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Ramucirumab(Day 1, Day 8, Day 43, Day 50, Day 85 and Day 92: End of Infusion)
- Number of Participants With Treatment Emergent Anti-Ramucirumab Antibodies (TE-ADA)(First dose to study completion plus 30-day safety follow-up (Up To 22 Months))