Study of Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes

Condition(s) targeted: Cancer; Solid Tumor

Intervention: IMC-1121B (Biological); Moxifloxacin (Drug); Diphenhydramine (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Eli Lilly and Company

Official(s) and/or principal investigator(s):
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), Study Director, Affiliation: Eli Lilly and Company

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

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 design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label

Primary outcome: Change From Baseline to Cycle 3 in QT/Corrected QT (QTc) Interval Prolongation in Participants

Secondary outcome:

Number of Participants With Drug-Related Adverse Events (AEs)

Maximum Concentration (Cmax) During Cycle 1

Maximum Concentration (Cmax) During Cycle 1, Day 4

Maximum Concentration (Cmax) During Cycle 1, Day 8

Maximum Concentration (Cmax) During Cycle 1, Day 15

Maximum Concentration (Cmax) During Cycle 2

Maximum Concentration (Cmax) During Cycle 3

Area Under Concentration (AUC) During Cycle 1

Area Under Concentration (AUC) During Cycle 1, Day 4

Area Under Concentration (AUC) During Cycle 1, Day 8

Area Under Concentration (AUC) During Cycle 1, Day 15

Area Under Concentration (AUC) During Cycle 2, Day 1

Area Under Concentration (AUC) During Cycle 3

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

ImClone Investigational Site, Atlanta, Georgia 30322, United States

ImClone Investigational Site, Metairie, Louisiana 70006, United States

ImClone Investigational Site, Ann Arbor, Michigan 48109, United States

ImClone Investigational Site, Philadelphia, Pennsylvania 19111, United States

ImClone Investigational Site, Providence, Rhode Island 02903, United States

ImClone Investigational Site, Houston, Texas 77024, United States

ImClone Investigational Site, Seattle, Washington 98109, United States

Starting date: November 2009
Last updated: May 15, 2015