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

NCT01515306 | Completed Phase 2 Results

• 3 other identifiers: 14432I4T-IE-JVCACP12-1032
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Malignant Solid Tumor

Keywords

Advanced Malignant Solid Tumors

Outcome Measures

Primary Outcomes (5)

• Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Paclitaxel From Time Zero to Infinity [AUC(0-∞)] in Cycle 1

  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.

  Cycle 1: 0, 1, 1.5, 2, 5, 7, 24, 48, 72 and 168 hours post paclitaxel infusion

• Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Paclitaxel From Time Zero to Infinity [AUC(0-∞)] in Cycle 2

  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.

  Cycle 2: -1, 0, 1, 1.5, 2, 5, 7, 24, 48, 72, 96, 168, 264 and 336 hours post paclitaxel infusion

• Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Paclitaxel in Cycle 1

  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.

  Cycle 1: 0,1, 1.5, 2, 5, 7, 24, 48, 72 and 168 hours post paclitaxel infusion

• Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Paclitaxel in Cycle 2

  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.

  Cycle 2: -1, 0, 1, 1.5, 2, 5, 7, 24, 48, 72, 96, 168, 264 and 336 hours post paclitaxel infusion

• Part B: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] as Monotherapy

  Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose.

  Cycle 1: 0,1, 1.5, 2, 5, 7, 24, 48, 72,168, 264, 336, 408, and 504 hours post ramucirumab infusion

Secondary Outcomes (4)

• 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

  Cycle 2: 0, 1, 2, 2.5, 3, 6, 8, 25, 49, 73, 97, 169, 265 and 337 hours post ramucirumab infusion

• Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Ramucirumab in the Presence of Paclitaxel

  Cycle 2: 0, 1, 2, 2.5, 3, 6, 8, 25, 49, 73, 97, 169, 265 and 337 hours post ramucirumab infusion

• Part A: Immunogenicity of Ramucirumab in Combination With Paclitaxel - Number of Participants With Anti-Ramucirumab Antibodies

  -1 hour on Day 1 of Cycle 2, and 30 days after last dose of study drug

• Part B: Immunogenicity of Ramucirumab as Monotherapy - Number of Participants With Anti-Ramucirumab Antibodies

  0 hour on Day 1 of Cycle 1, and 30 days after last dose of study drug

Study Arms (2)

Part A: ramucirumab (IMC-1121B) and paclitaxel

EXPERIMENTAL

Experimental: Part A: ramucirumab (IMC-1121B) and paclitaxel Cycle 1: paclitaxel administered on Day 1 of 2-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.

Biological: ramucirumab (IMC-1121B); Drug: paclitaxel

Part B: ramucirumab (IMC-1121B) and paclitaxel

EXPERIMENTAL

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); Drug: paclitaxel

Interventions

ramucirumab (IMC-1121B) BIOLOGICAL

ramucirumab (IMC-1121B) 8 milligrams/kilogram (mg/kg) intravenous infusion, administered on Day 1and Day 15 of each 4-week cycle, unless otherwise specified.

Also known as: LY3009806

Part A: ramucirumab (IMC-1121B) and paclitaxel; Part B: ramucirumab (IMC-1121B) and paclitaxel

paclitaxel DRUG

paclitaxel 80 milligrams/square meter (mg/m²) intravenous infusion, administered on Days 1, 8 and 15 of each 4-week cycle, unless otherwise specified.

Part A: ramucirumab (IMC-1121B) and paclitaxel; Part B: ramucirumab (IMC-1121B) and paclitaxel

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (6)

ImClone Investigational Site

Ann Arbor, Michigan, 48109, United States

Location

ImClone Investigational Site

Detroit, Michigan, 48202, United States

Location

ImClone Investigational Site

New Brunswick, New Jersey, 08901, United States

Location

ImClone Investigational Site

Cleveland, Ohio, 44195, United States

Location

ImClone Investigational Site

Philadelphia, Pennsylvania, 19111, United States

Location

ImClone Investigational Site

Seattle, Washington, 98109, United States

Location

MeSH Terms

Interventions

Ramucirumab; Paclitaxel

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

Results Point of Contact

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

ClinicalTrials.gov@lilly.com

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 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2012
• First Posted: January 24, 2012
• Study Start: July 19, 2012
• Primary Completion: March 20, 2013
• Study Completion: February 22, 2021
• Last Updated: March 8, 2022
• Results First Posted: June 18, 2014

Record last verified: 2022-02

Locations

US (6)