Overview

This trial is active, not recruiting.

Conditions cancer, solid tumor
Treatment imc-1121b
Phase phase 2
Target VEGF
Sponsor Eli Lilly and Company
Start date November 2009
End date April 2010
Trial size 68 participants
Trial identifier NCT01017731, 13915, CP12-0712, I4T-IE-JVBK

Summary

The purpose of this study is to determine if Ramucirumab (IMC-1121B) causes prolongation of the QT/QTc interval in participants with advanced cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Arm
(Experimental)
Active-control participants (first 16 participants) will receive one dose of moxifloxacin orally 7 days before the first treatment with ramucirumab. All participants will undergo triplicate electrocardiogram (ECG) tests (consisting of three individual ECGs performed consecutively within a period of 4 minutes) and vital signs at various times over the trial period. For Cycle 1, all participants will also receive 2 infusions of diphenhydramine before ramucirumab therapy (the first infusion is 1 day before therapy and the second infusion is 15 minutes before therapy). For Cycles 2, 3, and 4, all participants will receive diphenhydramine 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, diphenhydramine infusions before ramucirumab therapy are at the investigator's discretion. Ramucirumab [10 milligrams per kilogram (mg/kg)] intravenously over 60 minutes, once every 3 weeks for minimum of 9 weeks without a break in between.
imc-1121b Ramucirumab
IMC-1121B (Ramucirumab) 10 mg/kg intravenously over 60 minutes, once every 3 weeks for minimum of 9 weeks.

Primary Outcomes

Measure
Change From Baseline to Cycle 3 in QT/Corrected QT (QTc) Interval Prolongation in Participants
time frame: Baseline, Cycle 3 (1 cycle=21 days)

Secondary Outcomes

Measure
Number of Participants With Drug-Related Adverse Events (AEs)
time frame: Baseline up to data cut off (approximately 105.6 weeks)
Maximum Concentration (Cmax) During Cycle 1
time frame: Cycle 1 [2.25 hours (h), 3.25 h, 4.25 h, 72 h, 168 h, 336 h postdose]
Maximum Concentration (Cmax) During Cycle 1, Day 4
time frame: Approximately Week 1 (Cycle 1, Day 4)
Maximum Concentration (Cmax) During Cycle 1, Day 8
time frame: Approximately Week 2 (Cycle 1, Day 8)
Maximum Concentration (Cmax) During Cycle 1, Day 15
time frame: Approximately Week 3 (Cycle 1, Day 15)
Maximum Concentration (Cmax) During Cycle 2
time frame: Cycle 2 (predose and 1.25 hours postdose)
Maximum Concentration (Cmax) During Cycle 3
time frame: Cycle 3 [predose and 1.25 hours (h), 2.25 h, 3.25 h, 4.25 h, 72 h, 168 h, 336 h, and 504 h postdose]
Area Under Concentration (AUC) During Cycle 1
time frame: Cycle 1 [2.25 hours (h), 3.25 h, 4.25 h, 72 h, 168 h, 336 h postdose]
Area Under Concentration (AUC) During Cycle 1, Day 4
time frame: Approximately Week 1 (Cycle 1, Day 4)
Area Under Concentration (AUC) During Cycle 1, Day 8
time frame: Approximately Week 2 (Cycle 1, Day 8)
Area Under Concentration (AUC) During Cycle 1, Day 15
time frame: Approximately Week 3 (Cycle 1, Day 15)
Area Under Concentration (AUC) During Cycle 2, Day 1
time frame: Approximately Week 1 (Cycle 2, Day 1)
Area Under Concentration (AUC) During Cycle 3
time frame: Cycle 3 [predose and 1.25 hours (h), 2.25 h, 3.25 h, 4.25 h, 72 h, 168 h, 336 h, and 504 h postdose]

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - The participant has histologically documented advanced or metastatic malignant cancer of solid tumor origin which has not responded to standard therapy or for which no standard therapy is available - The participant has resolution of adverse events from prior anticancer therapies - Performance status of 0 to 2 - The participant is ≥ 18 years of age - The participant is able to provide informed written consent and is amenable to compliance with protocol schedules and testing - The participant has adequate liver, kidney, blood, and blood clotting functions as defined in trial entrance criteria - The participant agrees to use adequate contraception during the study period and for 8 weeks after the last dose of study treatment Exclusion Criteria: - The participant had anticancer therapy within 14 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study - The participant had therapeutic radiotherapy within 14 days prior to entering the study - The participant has ongoing side effects ≥ Grade 2 due to prior anticancer therapy - The participant has brain or leptomeningeal metastases - The participant has a history of uncontrolled or severe cardiac disease - The participant has a history of severe congestive heart failure (CHF) - The participant has a known history of arterial thrombotic events - The participant has a known history of significant peripheral arterial disease (PAD) - The participant has an implantable pacemaker or automatic implantable cardioverter defibrillator (AICD) - The participant has a history of risk factors for ventricular tachycardia or Torsades de pointes (TdP) [for example, family history (parents or siblings) of long QT syndrome], history of fainting, unexplained loss of consciousness, or convulsions - The participant has a systolic blood pressure (SBP) of > 150 millimeters of mercury (mmHg) or < 90 mmHg or a diastolic blood pressure (DBP) of < 45 or > 95 mmHg. (Participants with a history of hypertension who are receiving antihypertensive therapy are permitted on study provided blood pressure is within the parameters detailed above) - The participant has a heart rate < 50 beats per minute (bpm) or > 100 bpm at rest - The participant has a clinically relevant abnormality on the ECG, preventing an accurate measurement of the QT interval - The participant is using a medication that is known to prolong the ECG QT interval - The participant has a known allergy to any of the treatment components including fluoroquinolone antibiotics - The participant has received an investigational new drug or device within 14 days prior to enrollment into this study (excluding placement of an intravenous access device) - The participant has undergone major surgery within 28 days prior to enrollment - The participant has known human immunodeficiency virus (HIV) infection - The participant, if female, is pregnant or lactating - The participant is receiving chronic daily treatment with aspirin [> 325 milligrams per day (mg/day)] - The participant has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm - The participant has psychological, familial, sociological, or geographical conditions which do not permit adequate study follow-up, compliance with the protocol, or signature of Informed Consent

Additional Information

Official title A Study to Evaluate the Relationship Between Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes in Patients With Advanced Cancer
Description The primary purpose of this study is to determine if treatment with ramucirumab causes prolongation of the QTc/QT interval in participants with advanced cancer, to assess the safety and tolerability of ramucirumab therapy, and to evaluate the pharmacokinetic (PK) characteristics of ramucirumab
Trial information was received from ClinicalTrials.gov and was last updated in May 2014.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.