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

NCT01017731 | Completed Phase 2 Results

• 3 other identifiers: 13915CP12-0712I4T-IE-JVBK
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 7

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.

Conditions

Cancer; Solid Tumor

Keywords

Advanced Solid tumor; Antibodies, Monoclonal; QTc; Metastatic; Malignant

Outcome Measures

Primary Outcomes (1)

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

  All electrocardiogram (ECG) tests were performed in triplicate prior to ramucirumab treatment. QT is the interval between the Q and T waves and QTc is the QT corrected for heart rate using Fridericia's formula: QTc = QT/RR\^0.33 where RR is the interval between 2 R waves. Each participant's mean QT/QTc value was calculated for each ECG test during Cycle 3 and compared to his/her mean pretreatment QT/QTc value. The greatest change from baseline during Cycle 3 was reported. QTc prolongation is defined as a QTc exceeding 10 milliseconds (msec) with a lower 90% confidence interval (CI) exceeding 5 msec at any postdose time points per the International Conference on Harmonization (ICH) E14 guidelines for non-thorough QT studies (ICH 2005; ICH 2008). Least squares (LS) mean was calculated using a linear mixed model for repeated measures (MMRM) and adjusted for serum concentration.

  Baseline, Cycle 3 (1 cycle=21 days)

Secondary Outcomes (13)

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

  Baseline up to data cut off (approximately 105.6 weeks)

• Maximum Concentration (Cmax) During Cycle 1

  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

  Approximately Week 1 (Cycle 1, Day 4)

• Maximum Concentration (Cmax) During Cycle 1, Day 8

  Approximately Week 2 (Cycle 1, Day 8)

• Maximum Concentration (Cmax) During Cycle 1, Day 15

  Approximately Week 3 (Cycle 1, Day 15)

Study Arms (1)

IMC-1121B

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.

Biological: IMC-1121B; Drug: Moxifloxacin; Drug: Diphenhydramine

Interventions

IMC-1121B BIOLOGICAL

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

Also known as: Ramucirumab, LY3009806

IMC-1121B

Moxifloxacin DRUG

Administered orally

IMC-1121B

Diphenhydramine DRUG

Administered IV

IMC-1121B

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (7)

ImClone Investigational Site

Atlanta, Georgia, 30322, United States

Location

ImClone Investigational Site

Metairie, Louisiana, 70006, United States

Location

ImClone Investigational Site

Ann Arbor, Michigan, 48109, United States

Location

ImClone Investigational Site

Philadelphia, Pennsylvania, 19111, United States

Location

ImClone Investigational Site

Providence, Rhode Island, 02903, United States

Location

ImClone Investigational Site

Houston, Texas, 77024, United States

Location

ImClone Investigational Site

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 26984445 DERIVED

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Interventions

Ramucirumab; Moxifloxacin; Diphenhydramine

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

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

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: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2009
• First Posted: November 23, 2009
• Study Start: November 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: May 1, 2014
• Last Updated: June 10, 2015
• Results First Posted: June 18, 2014

Record last verified: 2015-05

Locations

US (7)