Clinical trial NCT01017731: Study of Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes
Official title: A Study to Evaluate the Relationship Between Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer
Solid Tumor
Keywords: Advanced Solid tumor
Antibodies, Monoclonal
QTc
Metastatic
Malignant
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2009-11-23
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline to Cycle 3 in QT/Corrected QT (QTc) Interval Prolongation in Participants
timeFrame: Baseline, Cycle 3 (1 cycle=21 days)
Secondary outcomes:
measure: Number of Participants With Drug-Related Adverse Events (AEs)
timeFrame: Baseline up to data cut off (approximately 105.6 weeks)
measure: Maximum Concentration (Cmax) During Cycle 1
timeFrame: Cycle 1 [2.25 hours (h), 3.25 h, 4.25 h, 72 h, 168 h, 336 h postdose]
measure: Maximum Concentration (Cmax) During Cycle 1, Day 4
timeFrame: Approximately Week 1 (Cycle 1, Day 4)
measure: Maximum Concentration (Cmax) During Cycle 1, Day 8
timeFrame: Approximately Week 2 (Cycle 1, Day 8)
measure: Maximum Concentration (Cmax) During Cycle 1, Day 15
timeFrame: Approximately Week 3 (Cycle 1, Day 15)
measure: Maximum Concentration (Cmax) During Cycle 2
timeFrame: Cycle 2 (predose and 1.25 hours postdose)
measure: Maximum Concentration (Cmax) During Cycle 3
timeFrame: 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]
measure: Area Under Concentration (AUC) During Cycle 1
timeFrame: Cycle 1 [2.25 hours (h), 3.25 h, 4.25 h, 72 h, 168 h, 336 h postdose]
measure: Area Under Concentration (AUC) During Cycle 1, Day 4
timeFrame: Approximately Week 1 (Cycle 1, Day 4)
measure: Area Under Concentration (AUC) During Cycle 1, Day 8
timeFrame: Approximately Week 2 (Cycle 1, Day 8)
measure: Area Under Concentration (AUC) During Cycle 1, Day 15
timeFrame: Approximately Week 3 (Cycle 1, Day 15)
measure: Area Under Concentration (AUC) During Cycle 2, Day 1
timeFrame: Approximately Week 1 (Cycle 2, Day 1)
measure: Area Under Concentration (AUC) During Cycle 3
timeFrame: 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]
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: ImClone Investigational Site
state: Georgia
city: Metairie
country: United States
facility: ImClone Investigational Site
state: Louisiana
city: Ann Arbor
country: United States
facility: ImClone Investigational Site
state: Michigan
city: Philadelphia
country: United States
facility: ImClone Investigational Site
state: Pennsylvania
city: Providence
country: United States
facility: ImClone Investigational Site
state: Rhode Island
city: Houston
country: United States
facility: ImClone Investigational Site
state: Texas
city: Seattle
country: United States
facility: ImClone Investigational Site
state: Washington
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: Olszanski AJ, Smith DC, Camacho LH, Thompson J, Ramalingam SS, Harvey RD, Campos L, Ferry D, Tang S, Gao L, Safran H. Electrocardiographic Characterization of Ramucirumab on the Corrected QT Interval in a Phase II Study of Patients With Advanced Solid Tumors. Oncologist. 2016 Apr;21(4):402-3. doi: 10.1634/theoncologist.2015-0467. Epub 2016 Mar 16.