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

• ClinicalTrials.gov Identifier: NCT02359058
• Recruitment Status: Completed
• First Posted: February 9, 2015
• Results First Posted: December 4, 2017
• Last Update Posted: January 24, 2018
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Stomach Neoplasms	Drug: Ramucirumab; Drug: Capecitabine; Drug: Cisplatin; Drug: S-1; Drug: Oxaliplatin	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1b Study of Ramucirumab in Combination With Fluoropyrimidines and Platinum-Based Agents in Japanese Patients With Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma
• Study Start Date: February 2015
• Actual Primary Completion Date: July 2016
• Actual Study Completion Date: November 2016

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: Ramucirumab; Administered IV; Other Names: LY3009806; IMC-1121B; Drug: Capecitabine; Administered orally; Drug: Cisplatin; Administered IV
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.	Drug: Ramucirumab; Administered IV; Other Names: LY3009806; IMC-1121B; Drug: Cisplatin; Administered IV; Drug: S-1; Administered orally
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.	Drug: Ramucirumab; Administered IV; Other Names: LY3009806; IMC-1121B; Drug: S-1; Administered orally; Drug: Oxaliplatin; Administered IV

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Ramucirumab [ Time Frame: Day 1, Day 8, Day 43, Day 50, Day 85 and Day 92: End of Infusion ]
   Maximum Serum Concentration (Cmax) of Ramucirumab.
2. Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) of Ramucirumab [ Time Frame: Day 8, Day 22, Day 29, Day 43, Day 50, Day 64, Day 71, Day 85, Day 92 and Day 106: Pre-Dose ]
   Minimum Serum Concentration (Cmin) of Ramucirumab.
3. Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate) [ Time Frame: First Dose to Date of Objective Progressive Disease or Death Due to Any Cause (Up To 22 Months) ]
   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.
4. Number of Participants With Treatment Emergent Anti-Ramucirumab Antibodies (TE-ADA) [ Time Frame: First dose to study completion plus 30-day safety follow-up (Up To 22 Months) ]
   Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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) v1.1.
• 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.

Contacts and Locations

Locations

Japan

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician.

Aichi, Japan, 464-8681

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician.

Chiba, Japan, 277-8577

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician.

Ehime, Japan, 791-0280

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician

Osaka, Japan, 565-0871

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST); Eli Lilly and Company

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02359058
• Other Study ID Numbers: 15532; I4T-JE-JVCX ( Other Identifier: Eli Lilly )
• First Posted: February 9, 2015
• Results First Posted: December 4, 2017
• Last Update Posted: January 24, 2018
• Last Verified: July 2017

Additional relevant MeSH terms:

Stomach Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Capecitabine; Oxaliplatin; Ramucirumab; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action