A Study of Ramucirumab (IMC-1121B) and Paclitaxel in Participants With Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01515306
First received: January 18, 2012
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to investigate whether there are no clinically significant pharmacokinetic effects of concomitant ramucirumab (IMC-1121B) on paclitaxel by investigating the pharmacokinetics (PK) of each in participants with advanced malignant solid tumors.

Part A of this study will investigate the potential of concomitant ramucirumab (IMC-1121B) to affect the pharmacokinetics of paclitaxel. Part B of this study will investigate the pharmacokinetics of ramucirumab (IMC-1121B) as monotherapy.


Condition Intervention Phase
Malignant Solid Tumor
Biological: ramucirumab (IMC-1121B)
Drug: paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study to Evaluate the Potential of Concomitant Ramucirumab to Affect the Pharmacokinetics of Paclitaxel in Patients With Advanced Malignant Solid Tumors

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Paclitaxel From Time Zero to Infinity [AUC(0-∞)] in Cycle 1 [ Time Frame: Cycle 1: 0, 1, 1.5, 2, 5, 7, 24, 48, 72 and 168 hours post paclitaxel infusion ] [ Designated as safety issue: No ]
    Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error.

  • Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Paclitaxel From Time Zero to Infinity [AUC(0-∞)] in Cycle 2 [ Time Frame: Cycle 2: -1, 0, 1, 1.5, 2, 5, 7, 24, 48, 72, 96, 168, 264 and 336 hours post paclitaxel infusion ] [ Designated as safety issue: No ]
    Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error.

  • Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Paclitaxel in Cycle 1 [ Time Frame: Cycle 1: 0,1, 1.5, 2, 5, 7, 24, 48, 72 and 168 hours post paclitaxel infusion ] [ Designated as safety issue: No ]
    Dose-normalized Cmax was calculated from Cmax divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error.

  • Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Paclitaxel in Cycle 2 [ Time Frame: Cycle 2: -1, 0, 1, 1.5, 2, 5, 7, 24, 48, 72, 96, 168, 264 and 336 hours post paclitaxel infusion ] [ Designated as safety issue: No ]
    Dose-normalized Cmax was calculated from Cmax divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error.

  • Part B: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] as Monotherapy [ Time Frame: Cycle 1: 0,1, 1.5, 2, 5, 7, 24, 48, 72,168, 264, 336, 408, and 504 hours post ramucirumab infusion ] [ Designated as safety issue: No ]
    Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose.


Secondary Outcome Measures:
  • Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] in the Presence of Paclitaxel [ Time Frame: Cycle 2: 0, 1, 2, 2.5, 3, 6, 8, 25, 49, 73, 97, 169, 265 and 337 hours post ramucirumab infusion ] [ Designated as safety issue: No ]
    Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose.

  • Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Ramucirumab in the Presence of Paclitaxel [ Time Frame: Cycle 2: 0, 1, 2, 2.5, 3, 6, 8, 25, 49, 73, 97, 169, 265 and 337 hours post ramucirumab infusion ] [ Designated as safety issue: No ]
    Dose-normalized Cmax was calculated from Cmax divided by the dose.

  • Part A: Immunogenicity of Ramucirumab in Combination With Paclitaxel - Incidence of Anti-Ramucirumab Antibodies [ Time Frame: -1 hour on Day 1 of Cycle 2, and 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]
  • Part B: Immunogenicity of Ramucirumab as Monotherapy - Incidence of Anti-Ramucirumab Antibodies [ Time Frame: 0 hour on Day 1 of Cycle 1, and 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: July 2012
Estimated Study Completion Date: September 2014
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A: ramucirumab (IMC-1121B) and paclitaxel

Cycle 1: paclitaxel administered on Day 1 of 2-week cycle.

Cycle 2: ramucirumab (IMC-1121B) administered on Day 1 and Day 15, paclitaxel administered on Day 1, Day 8 and Day 15 of 4-week cycle.

Cycle 3 and beyond: ramucirumab (IMC-1121B) administered on Day 1 and Day 15, paclitaxel administered on Day 1, Day 8 and Day 15 of each 4-week cycle.

Biological: ramucirumab (IMC-1121B)
ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) intravenous infusion, administered on Day 1and Day 15 of each 4-week cycle, unless otherwise specified.
Other Name: LY3009806
Drug: paclitaxel
paclitaxel 80 milligrams/square meter (mg/m²) intravenous infusion, administered on Days 1, 8 and 15 of each 4-week cycle, unless otherwise specified.
Experimental: Part B: ramucirumab (IMC-1121B) and paclitaxel

Cycle 1: ramucirumab (IMC-1121B) administered as monotherapy on Day 1 of 3-week cycle.

Cycle 2 and beyond: ramucirumab (IMC-1121B) administered on Day 1 and Day 15, paclitaxel administered on Day 1, Day 8 and Day 15 of 4-week cycle.

*After Cycle 1 (mandatory pharmacokinetic phase) is completed, participants may continue to receive ramucirumab (IMC-1121B) monotherapy or combination therapy with paclitaxel as described in Part A.

Biological: ramucirumab (IMC-1121B)
ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) intravenous infusion, administered on Day 1and Day 15 of each 4-week cycle, unless otherwise specified.
Other Name: LY3009806
Drug: paclitaxel
paclitaxel 80 milligrams/square meter (mg/m²) intravenous infusion, administered on Days 1, 8 and 15 of each 4-week cycle, unless otherwise specified.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has histologic or cytologic documentation of a malignant solid tumor
  • Has an advanced solid tumor that is refractory to standard therapy or for which no standard therapy is available
  • Part A only: Has had 0-1 prior taxane-containing treatment regimens (including taxane monotherapy), which must have been completed at least 6 months before the first dose of study medication (prior bevacizumab is allowed)
  • Part B only: Prior bevacizumab- and taxane-containing treatment regimens (including taxane monotherapy) are allowed, provided these regimens have been completed at least 6 months before the first dose of study medication
  • Has resolution to Grade ≤ 1 of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy with the exception of peripheral neuropathy, which must not have exceeded Grade 1, by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v 4.0)
  • Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 - 2
  • Has adequate hematologic function. Blood transfusion is allowed but must be completed 48 hours before study drug administration
  • Has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal [ULN], aspartate transaminase [AST] and alanine transaminase [ALT] ≤ 1.5 x ULN
  • Has serum creatinine ≤ 1.5 x ULN. If serum creatinine > 1.5 x ULN, the calculated creatinine clearance (CrCl) should be ≥ 40 milliliter/minute (mL/min)
  • Urinary protein is <2+ on dipstick or routine urinalysis (UA)
  • Must have adequate coagulation function as defined by an international normalized ratio (INR) of ≤ 1.5 and a partial thromboplastin time (PTT) or an activated PTT (aPTT) ≤ 1.5 x ULN
  • Eligible participants of reproductive potential agree to use adequate method of contraception during the study period and for 12 weeks after the last dose of study medication

Exclusion Criteria:

  • Is receiving concomitant therapy with clinically relevant inhibitors or inducers of cytochrome P450, CYP2C8, CYP3AY and/or isoenzymes
  • Are currently enrolled in, or discontinued within the last 14 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
  • Has received a monoclonal antibody within 42 days prior to first dose of study medication
  • Has received radiotherapy within 14 days prior to first dose of study medication
  • Has received cytotoxic chemotherapy within 21 days (6 weeks for nitrosoureas or mitomycin C) prior to first dose of study medication
  • Has a cardiac left ventricular ejection fraction (LVEF) not within institutional limits of normal on a multigated acquisition scan (MUGA) or echocardiogram
  • Is receiving concurrent treatment with another anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, radiation therapy, chemoembolization, targeted or other investigational anticancer therapy
  • Is receiving chronic therapy with nonsteroidal anti-inflammatory agents or other antiplatelet agents. Aspirin use at doses up to 325 milligrams/day (mg/day) and analgesic agents with no or low bleeding risk are permitted
  • Has a history of uncontrolled hereditary or acquired bleeding or thromboembolic disorders
  • Has experienced any arterial thromboembolic event, including myocardial infarction (MI), unstable angina stroke or transient ischemic attack (TIA), within 6 months prior to first dose of study medication
  • Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the 3 months prior to first dose of study medication
  • Has experienced a Grade 3 or 4 hemorrhagic event within 3 months prior to first dose of study medication
  • Has experienced peripheral neuropathy ≥ Grade 2 at any time prior to study entry
  • Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea
  • History of gastrointestinal perforation and / or fistulae within 6 months prior to randomization
  • Has an ongoing or active infection requiring treatment with intravenous antibiotics
  • Has a serious or nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to first dose of study medication
  • Has uncontrolled hypertension
  • Has symptomatic congestive heart failure
  • Has known brain or leptomeningeal disease
  • Has known positive status for human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome-related illness
  • Has known active drug or alcohol abuse that would affect participant's ability to comply with study treatment
  • Has pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
  • Has had major surgery within 28 days prior to first dose of study medication or subcutaneous venous access device implantation within 7 days prior to first dose of study medication
  • Has an elective or planned major surgery during the course of the trial
  • If a primary cancer is non-small-cell lung cancer (NSCLC), participant has intratumor cavitation, radiologically documented evidence of major blood vessel invasion or encasement by cancer, or proximity of cancer to major airways
  • Has received prior ramucirumab (IMC-1121B) therapy
  • The participant has:

    • cirrhosis at a level of Child-Pugh B (or worse)
    • cirrhosis (any degree) and a history of hepatic encephalopathy or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
  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: NCT01515306

Locations
United States, Michigan
ImClone Investigational Site
Ann Arbor, Michigan, United States, 48109
ImClone Investigational Site
Detroit, Michigan, United States, 48202
United States, New Jersey
ImClone Investigational Site
New Brunswick, New Jersey, United States, 08901
United States, Ohio
ImClone Investigational Site
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
ImClone Investigational Site
Philadelphia, Pennsylvania, United States, 19111
United States, Washington
ImClone Investigational Site
Seattle, Washington, United States, 98109
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: NCT01515306     History of Changes
Other Study ID Numbers: 14432, I4T-IE-JVCA, CP12-1032
Study First Received: January 18, 2012
Results First Received: May 16, 2014
Last Updated: May 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Advanced Malignant Solid Tumors

Additional relevant MeSH terms:
Neoplasms
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014