Study of Weekly Paclitaxel With Ramucirumab in Participants With Advanced Gastric Adenocarcinomas

Phase 1

Completed

• Conditions: Adenocarcinoma
• Interventions: Biological: Ramucirumab (IMC-1121B ); Drug: Paclitaxel

• Registration Number: NCT01253525
• Lead Sponsor: Eli Lilly and Company

Brief Summary

Investigate the safety and tolerability of ramucirumab (IMC-1121B) drug product (DP) in combination with paclitaxel.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-11
• Study First Submitted: 2010-12-02
• Study First Submitted QC: 2010-12-02
• Study First Posted: 2010-12-03
• Primary Completion: 2011-10
• Study Completion: 2011-10
• Status Verified: 2014-05
• Results First Submitted: 2014-05-16
• Results First Submitted QC: 2014-05-16
• Last Update Submitted: 2014-05-16
• Results First Posted: 2014-06-18
• Last Update Posted: 2014-06-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

• Has a histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma
• Has an advanced or metastatic solid gastric adenocarcinoma that has failed standard therapy
• Has resolution of all clinically significant toxic effects of prior therapy, surgery, treatment with an investigational agent or device, treatment monoclonal antibody or small molecule, and radiotherapy or chemotherapy.
• Has adequate organ function
• Eligible participants of reproductive potential (both sexes) agree to use adequate contraceptive methods (hormonal or barrier methods) during the study period and for 12 weeks after the last dose of study medication

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Exclusion Criteria

• Has undergone major surgery within 28 days prior to the study, or subcutaneous venous access device placement within 7 days prior to the study registration date
• Has elective or planned surgery to be conducted during the trial
• Has had treatment with an investigational agent or device, an antineoplastic small molecule, or antineoplastic radiotherapy or chemotherapy
• Was previously treated with a chemotherapy regimen containing nitrosoureas or mitomycin C
• Has had treatment with an antineoplastic monoclonal antibody within 8 weeks prior to the study registration date
• Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism prior to the study registration date
• Has experienced any arterial thrombotic event, including myocardial infarction, cerebrovascular accident, or transient ischemic attack, within 6 months prior to the study date
• Is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin or similar agents. (Participants receiving prophylactic, low-dose anticoagulation therapy are eligible provided that the coagulation parameters International Normalized Ratio (INR) ≤ 1.5, prothrombin time (PT) and partial thromboplastin time (PTT) or - Is receiving chronic therapy with nonsteroidal anti-inflammatory agents [Aspirin use at doses up to 325 milligrams/day (mg/day) is permitted]
• Has significant bleeding disorders, vasculitis, history of postoperative bleeding complications, hemoptysis or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to the study date
• Has a history of GI perforation and/or fistulae within 6 months prior to the study date
• Has symptomatic congestive heart failure, unstable angina pectoris, or symptomatic or poorly controlled cardiac arrhythmia
• Has uncontrolled arterial hypertension despite standard medical management.
• Has a serious or nonhealing wound or peptic ulcer or bone fracture within 28 days prior to the study date
• Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea
• Has a serious illness or medical condition(s)
• Is pregnant or lactating
• Has received treatment with another investigational drug or participation in another interventional clinical trial within 28 days prior to the study date

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ramucirumab (IMC-1121B ) and Pacitaxel	Ramucirumab (IMC-1121B )	Each treatment cycle is 4 weeks (28 days)
Ramucirumab (IMC-1121B ) and Pacitaxel	Paclitaxel	Each treatment cycle is 4 weeks (28 days)

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1	Cycle 1 of 28-day cycle	DLT based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE v4.02) in Cycle (Cy) 1 due to study drug (SD) with (w/): Grade (Gr) ≥3 neutropenia w/fever ≥38.5°C or w/bacteremia or sepsis, thrombocytopenia w/bleeding and platelet substitution, prothrombin and/or partial thromboplastin time w/no anticoagulation, hyperbilirubinemia; Gr 4: neutropenia \>5 days, thrombocytopenia, Gr 4 or uncontrollable hypertension QTc\>500 milliseconds (ms) or increase ≥100 ms increase in 24 hours after SD or significant arrhythmia in this period; Gr ≥3 nonhematologic toxicity (tox), excluding Gr 3 hypersensitivity, hypertension, injection-site reaction, arthralgia/myalgia, asthenia/fatigue, diarrhea w/out loperamide/nausea/vomiting w/out antiemetic and transient aminotransferase elevation. SD tox=delay \>1 week in ramucirumab (RAM) dose or omission of 1 dose of RAM or 2 paclitaxel doses due to tox in Cy 1 or delay \>2 weeks between Cy 1 and Cy 2 due to persistent tox.
Number of Participants With Adverse Events (AEs)	Up to 47 weeks post baseline	The number of participants who experienced AEs of any grade, AEs of Grade ≥3 or AEs resulting in death that were considered to be related to ramucirumab \[RAM (IMC-1121B)\] or paclitaxel (PAC). A summary of serious adverse events (SAEs) and all other non-SAEs, regardless of causality, is located in the Reported Adverse Events module.
Number of Participants With Serious Adverse Events (SAEs)	Up to 47 weeks post baseline	The number of participants who experienced SAEs that were considered to be related to ramucirumab \[RAM (IMC-1121B)\] or paclitaxel (PAC). A summary of SAEs and all other non-SAEs, regardless of causality, is located in the Reported Adverse Events module.

Secondary Outcome Measures

Name	Time	Method
Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 1	Cycle 1 Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	Cmax after a single dose of ramucirumab (IMC-1121B).
Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 1	Cycle 1 Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	AUC from time 0 to infinity (0-∞) after a single dose of ramucirumab (IMC-1121B).
Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 4	Cycle 4: Pre-infusion, Day 1 of 28-day cycle	Due to sparse pharmacokinetic sampling ramucirumab (IMC-1121B) Cmax could not be calculated in Cycle 4.
Ramucirumab Half-Life (t1/2) for Cycle 1	Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	Terminal t1/2 (the time it takes for the concentration of ramucirumab (IMC-1121B) in plasma or serum to decline by 50%) after a single dose of ramucirumab (IMC-1121B).
Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 3	Cycle 3: Pre-infusion, Day 1 of 28-day cycle	Due to the sparse pharmacokinetic sampling ramucirumab (IMC-1121B) AUC within the dosing interval (0-τ) could not be calculated in Cycle 3.
Ramucirumab Half-Life (t 1/2) for Cycle 3	Cycle 3: Pre-infusion, Day 1 of 28-day cycle	Due to sparse pharmacokinetic sampling ramucirumab (IMC-1121B) t1/2 could not be calculated in Cycle 3.
Ramucirumab Clearance (CL) for Cycle 3	Cycle 3: Pre-infusion, Day 1 of 28-day cycle	Due to sparse pharmacokinetic sampling CL could not be calculated for ramucirumab (IMC-1121B) in Cycle 3.
Ramucirumab Steady State Volume of Distribution (Vss) for Cycle 3	Cycle 3: Pre-infusion, Day 1 of 28-day cycle	Due to sparse pharmacokinetic sampling Vss for ramucirumab (IMC-1121B) could not be calculated in Cycle 3.
Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 4	Cycle 4: Pre-infusion, Day 1 of 28-day cycle	Due to sparse pharmacokinetic sampling AUC within the dosing interval (0-τ) for ramucirumab (IMC-1121B) could not be calculated in Cycle 4.
Ramucirumab Half-Life (t 1/2) for Cycle 4	Cycle 4: Pre-infusion, Day 1 of 28-day cycle	Due to sparse pharmacokinetic sampling t1/2 for ramucirumab (IMC-1121B) could not be calculated in Cycle 4.
Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity)	Cycle 1 through Cycle 5 (28-day cycles)	The percentage of participants who were treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies.
Ramucirumab Clearance (CL) or Cycle 1	Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	CL \[the volume of plasma or serum cleared of ramucirumab (IMC-1121B) per unit time\] after a single dose of ramucirumab (IMC-1121B).
Ramucirumab Steady State Volume of Distribution (Vss) for Cycle 1	Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	Vss \[distribution of ramucirumab (IMC-1121B) in the body at steady state\] after a single dose of ramucirumab (IMC-1121B).
Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 2	Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	Cmax after multiple doses of ramucirumab (IMC-1121B).
Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 2	Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	AUC within the dosing interval (0-τ) after multiple doses of ramucirumab (IMC-1121B).
Ramucirumab Half-Life (t1/2) for Cycle 2	Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	Terminal t1/2 \[the time it takes for the concentration of ramucirumab (IMC-1121B) in plasma or serum to decline by 50%\] after multiple doses of ramucirumab(IMC-1121B).
Ramucirumab Clearance (CL) for Cycle 2	Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	CL \[the volume of plasma or serum cleared of ramucirumab (IMC-1121B) per unit time\] at steady state after multiple doses of ramucirumab (IMC-1121B).
Ramucirumab Steady State Volume of Distribution (Vss) for Cycle 2	Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	Vss \[distribution of ramucirumab (IMC-1121B) in in the body at steady state\] is not calculated for multiple doses of ramucirumab (IMC-1121B).
Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 3	Cycle 3: Pre-infusion, Day 1 of 28-day cycle	Due to sparse pharmacokinetic sampling ramucirumab (IMC-1121B) Cmax could not be calculated in Cycle 3.
Ramucirumab Clearance (CL) for Cycle 4	Cycle 4: Pre-infusion, Day 1 of 28-day cycle	Due to sparse pharmacokinetic sampling CL for ramucirumab (IMC-1121B) could not be calculated in Cycle 4.
Ramucirumab Steady State Volume of Distribution (Vss) for Cycle 4	Cycle 4: Pre-infusion, Day 1 of 28-day cycle	Due to sparse pharmacokinetic sampling Vss for ramucirumab (IMC-1121B) could not be calculated in Cycle 4.

Trial Locations

Locations (1)

ImClone Investigational Site; 🇯🇵 Osaka, Japan