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

NCT01253525 | Completed Phase 1 Results

• 3 other identifiers: 14204CP12-1026I4T-IE-JVBW
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Adenocarcinoma

Keywords

Adenocarcinoma; Gastroesophageal Junction

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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

Secondary Outcomes (21)

• 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

• Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity)

  Cycle 1 through Cycle 5 (28-day cycles)

• 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

• 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

• Ramucirumab Clearance (CL) or Cycle 1

  Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle

Study Arms (1)

Ramucirumab (IMC-1121B ) and Pacitaxel

EXPERIMENTAL

Each treatment cycle is 4 weeks (28 days)

Biological: Ramucirumab (IMC-1121B ); Drug: Paclitaxel

Interventions

Ramucirumab (IMC-1121B ) BIOLOGICAL

8 milligrams/kilogram (mg/kg) intravenously on Days 1 and 15 of each 28-ay cycle

Also known as: LY3009806, IMC-1121B

Ramucirumab (IMC-1121B ) and Pacitaxel

Paclitaxel DRUG

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

Ramucirumab (IMC-1121B ) and Pacitaxel

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (3)

ImClone Investigational Site

Chiba, 277-8577, Japan

Location

ImClone Investigational Site

Osaka, 569-8686, Japan

Location

ImClone Investigational Site

Osaka, 589-5811, Japan

Location

Related Publications (1)

• Ueda S, Satoh T, Gotoh M, Gao L, Doi T. A phase ib study of safety and pharmacokinetics of ramucirumab in combination with paclitaxel in patients with advanced gastric adenocarcinomas. Oncologist. 2015 May;20(5):493-4. doi: 10.1634/theoncologist.2014-0440. Epub 2015 Apr 17.

  PMID: 25888272 DERIVED

MeSH Terms

Conditions

Adenocarcinoma

Interventions

Ramucirumab; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

Cycle 3 and beyond pharmacokinetic sampling was collected per the protocol-defined limited sampling schedule.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2010
• First Posted: December 3, 2010
• Study Start: November 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: June 18, 2014
• Results First Posted: June 18, 2014

Record last verified: 2014-05

Locations

JP (3)