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

Adenocarcinoma Clinical Trial

Official title:

A Phase 1b Study of Weekly Paclitaxel With Ramucirumab (IMC-1121B) Drug Product in Patients With Advanced Gastric Adenocarcinomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01253525
• Other study ID #: 14204
• Secondary ID: CP12-1026I4T-IE-
• Status: Completed
• Phase: Phase 1
• First received: December 2, 2010
• Last updated: May 16, 2014
• Start date: November 2010
• Est. completion date: October 2011

Study information

• Verified date: May 2014
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma

Intervention

Biological:
• Ramucirumab (IMC-1121B )
8 milligrams/kilogram (mg/kg) intravenously on Days 1 and 15 of each 28-ay cycle

Drug:
• Paclitaxel
80 milligram/square meter (mg/m2) intravenously Days 1, 8, and 15 of each 28 day cycle

Locations

Country	Name	City	State
Japan	ImClone Investigational Site	Chiba
Japan	ImClone Investigational Site	Osaka
Japan	ImClone Investigational Site	Osaka

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1	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.	Cycle 1 of 28-day cycle	Yes
Primary	Number of Participants With Adverse Events (AEs)	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.	Up to 47 weeks post baseline	Yes
Primary	Number of Participants With Serious Adverse Events (SAEs)	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.	Up to 47 weeks post baseline	Yes
Secondary	Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 1	Cmax after a single dose of ramucirumab (IMC-1121B).	Cycle 1 Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	No
Secondary	Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity)	The percentage of participants who were treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies.	Cycle 1 through Cycle 5 (28-day cycles)	No
Secondary	Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 1	AUC from time 0 to infinity (0-8) after a single dose of ramucirumab (IMC-1121B).	Cycle 1 Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	No
Secondary	Ramucirumab Half-Life (t1/2) for Cycle 1	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).	Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	No
Secondary	Ramucirumab Clearance (CL) or Cycle 1	CL [the volume of plasma or serum cleared of ramucirumab (IMC-1121B) per unit time] after a single dose of ramucirumab (IMC-1121B).	Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	No
Secondary	Ramucirumab Steady State Volume of Distribution (Vss) for Cycle 1	Vss [distribution of ramucirumab (IMC-1121B) in the body at steady state] after a single dose of ramucirumab (IMC-1121B).	Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	No
Secondary	Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 2	Cmax after multiple doses of ramucirumab (IMC-1121B).	Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	No
Secondary	Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 2	AUC within the dosing interval (0-t) after multiple doses of ramucirumab (IMC-1121B).	Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	No
Secondary	Ramucirumab Half-Life (t1/2) for Cycle 2	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).	Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	No
Secondary	Ramucirumab Clearance (CL) for Cycle 2	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).	Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	No
Secondary	Ramucirumab Steady State Volume of Distribution (Vss) for Cycle 2	Vss [distribution of ramucirumab (IMC-1121B) in in the body at steady state] is not calculated for multiple doses of ramucirumab (IMC-1121B).	Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle	No
Secondary	Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 3	Due to sparse pharmacokinetic sampling ramucirumab (IMC-1121B) Cmax could not be calculated in Cycle 3.	Cycle 3: Pre-infusion, Day 1 of 28-day cycle	No
Secondary	Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 3	Due to the sparse pharmacokinetic sampling ramucirumab (IMC-1121B) AUC within the dosing interval (0-t) could not be calculated in Cycle 3.	Cycle 3: Pre-infusion, Day 1 of 28-day cycle	No
Secondary	Ramucirumab Half-Life (t 1/2) for Cycle 3	Due to sparse pharmacokinetic sampling ramucirumab (IMC-1121B) t1/2 could not be calculated in Cycle 3.	Cycle 3: Pre-infusion, Day 1 of 28-day cycle	No
Secondary	Ramucirumab Clearance (CL) for Cycle 3	Due to sparse pharmacokinetic sampling CL could not be calculated for ramucirumab (IMC-1121B) in Cycle 3.	Cycle 3: Pre-infusion, Day 1 of 28-day cycle	No
Secondary	Ramucirumab Steady State Volume of Distribution (Vss) for Cycle 3	Due to sparse pharmacokinetic sampling Vss for ramucirumab (IMC-1121B) could not be calculated in Cycle 3.	Cycle 3: Pre-infusion, Day 1 of 28-day cycle	No
Secondary	Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 4	Due to sparse pharmacokinetic sampling ramucirumab (IMC-1121B) Cmax could not be calculated in Cycle 4.	Cycle 4: Pre-infusion, Day 1 of 28-day cycle	No
Secondary	Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 4	Due to sparse pharmacokinetic sampling AUC within the dosing interval (0-t) for ramucirumab (IMC-1121B) could not be calculated in Cycle 4.	Cycle 4: Pre-infusion, Day 1 of 28-day cycle	No
Secondary	Ramucirumab Half-Life (t 1/2) for Cycle 4	Due to sparse pharmacokinetic sampling t1/2 for ramucirumab (IMC-1121B) could not be calculated in Cycle 4.	Cycle 4: Pre-infusion, Day 1 of 28-day cycle	No
Secondary	Ramucirumab Clearance (CL) for Cycle 4	Due to sparse pharmacokinetic sampling CL for ramucirumab (IMC-1121B) could not be calculated in Cycle 4.	Cycle 4: Pre-infusion, Day 1 of 28-day cycle	No
Secondary	Ramucirumab Steady State Volume of Distribution (Vss) for Cycle 4	Due to sparse pharmacokinetic sampling Vss for ramucirumab (IMC-1121B) could not be calculated in Cycle 4.	Cycle 4: Pre-infusion, Day 1 of 28-day cycle	No