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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01253525
First received: December 2, 2010
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
Adenocarcinoma
Biological: Ramucirumab (IMC-1121B )
Drug: Paclitaxel
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Study of Weekly Paclitaxel With Ramucirumab (IMC-1121B) Drug Product in Patients With Advanced Gastric Adenocarcinomas

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1 [ Time Frame: Cycle 1 of 28-day cycle ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Up to 47 weeks post baseline ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Up to 47 weeks post baseline ] [ Designated as safety issue: Yes ]
    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:
  • Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 1 [ Time Frame: Cycle 1 Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle ] [ Designated as safety issue: No ]
    Cmax after a single dose of ramucirumab (IMC-1121B).

  • Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity) [ Time Frame: Cycle 1 through Cycle 5 (28-day cycles) ] [ Designated as safety issue: No ]
    The percentage of participants who were treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies.

  • Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 1 [ Time Frame: Cycle 1 Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle ] [ Designated as safety issue: No ]
    AUC from time 0 to infinity (0-∞) after a single dose of ramucirumab (IMC-1121B).

  • Ramucirumab Half-Life (t1/2) for Cycle 1 [ Time Frame: Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle ] [ Designated as safety issue: No ]
    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 Clearance (CL) or Cycle 1 [ Time Frame: Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle ] [ Designated as safety issue: No ]
    Cmax after multiple doses of ramucirumab (IMC-1121B).

  • Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 2 [ Time Frame: Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle ] [ Designated as safety issue: No ]
    AUC within the dosing interval (0-τ) after multiple doses of ramucirumab (IMC-1121B).

  • Ramucirumab Half-Life (t1/2) for Cycle 2 [ Time Frame: Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 3: Pre-infusion, Day 1 of 28-day cycle ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic sampling ramucirumab (IMC-1121B) Cmax could not be calculated in Cycle 3.

  • Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 3 [ Time Frame: Cycle 3: Pre-infusion, Day 1 of 28-day cycle ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 3: Pre-infusion, Day 1 of 28-day cycle ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic sampling ramucirumab (IMC-1121B) t1/2 could not be calculated in Cycle 3.

  • Ramucirumab Clearance (CL) for Cycle 3 [ Time Frame: Cycle 3: Pre-infusion, Day 1 of 28-day cycle ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 3: Pre-infusion, Day 1 of 28-day cycle ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic sampling Vss for ramucirumab (IMC-1121B) could not be calculated in Cycle 3.

  • Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 4 [ Time Frame: Cycle 4: Pre-infusion, Day 1 of 28-day cycle ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic sampling ramucirumab (IMC-1121B) Cmax could not be calculated in Cycle 4.

  • Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 4 [ Time Frame: Cycle 4: Pre-infusion, Day 1 of 28-day cycle ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 4: Pre-infusion, Day 1 of 28-day cycle ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic sampling t1/2 for ramucirumab (IMC-1121B) could not be calculated in Cycle 4.

  • Ramucirumab Clearance (CL) for Cycle 4 [ Time Frame: Cycle 4: Pre-infusion, Day 1 of 28-day cycle ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 4: Pre-infusion, Day 1 of 28-day cycle ] [ Designated as safety issue: No ]
    Due to sparse pharmacokinetic sampling Vss for ramucirumab (IMC-1121B) could not be calculated in Cycle 4.


Enrollment: 6
Study Start Date: November 2010
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ramucirumab (IMC-1121B ) and Pacitaxel
Each treatment cycle is 4 weeks (28 days)
Biological: Ramucirumab (IMC-1121B )
8 milligrams/kilogram (mg/kg) intravenously on Days 1 and 15 of each 28-ay cycle
Other Names:
  • LY3009806
  • IMC-1121B
Drug: Paclitaxel
80 milligram/square meter (mg/m2) intravenously Days 1, 8, and 15 of each 28 day cycle

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01253525

Locations
Japan
ImClone Investigational Site
Chiba, Japan, 277-8577
ImClone Investigational Site
Osaka, Japan, 589-5811
ImClone Investigational Site
Osaka, Japan, 569-8686
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 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01253525     History of Changes
Other Study ID Numbers: 14204, CP12-1026, I4T-IE-JVBW
Study First Received: December 2, 2010
Results First Received: May 16, 2014
Last Updated: May 16, 2014
Health Authority: Japan: Institutional Review Board

Keywords provided by Eli Lilly and Company:
Adenocarcinoma
Gastroesophageal Junction

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 20, 2014