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

NCT ID: NCT01017731

Last Updated: 2015-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2014-05-31

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

Conditions

Cancer; Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Blinding Strategy: NONE

Study Groups

IMC-1121B

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.

Group Type: EXPERIMENTAL

IMC-1121B

Intervention Type: BIOLOGICAL

IMC-1121B (Ramucirumab) 10 mg/kg intravenously (IV) over 60 minutes, once every 3 weeks for minimum of 9 weeks.

Moxifloxacin

Intervention Type: DRUG

Administered orally

Diphenhydramine

Intervention Type: DRUG

Administered IV

Interventions

IMC-1121B

IMC-1121B (Ramucirumab) 10 mg/kg intravenously (IV) over 60 minutes, once every 3 weeks for minimum of 9 weeks.

Intervention Type: BIOLOGICAL

Moxifloxacin

Administered orally

Intervention Type: DRUG

Diphenhydramine

Administered IV

Intervention Type: DRUG

Other Intervention Names

Ramucirumab; LY3009806

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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

Eli Lilly and Company

Locations

ImClone Investigational Site

Atlanta, Georgia, United States

ImClone Investigational Site

Metairie, Louisiana, United States

ImClone Investigational Site

Ann Arbor, Michigan, United States

ImClone Investigational Site

Philadelphia, Pennsylvania, United States

ImClone Investigational Site

Providence, Rhode Island, United States

ImClone Investigational Site

Houston, Texas, United States

ImClone Investigational Site

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26984445 (View on PubMed)

Other Identifiers

CP12-0712

Identifier Type: OTHER

Identifier Source: secondary_id

I4T-IE-JVBK

Identifier Type: OTHER

Identifier Source: secondary_id

13915

Identifier Type: -

Identifier Source: org_study_id