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

Cancer Clinical Trial

Official title:

A Study to Evaluate the Relationship Between Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes in Patients With Advanced Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01017731
• Other study ID #: 13915
• Secondary ID: CP12-0712I4T-IE-
• Status: Completed
• Phase: Phase 2
• First received: November 19, 2009
• Last updated: May 15, 2015
• Start date: November 2009
• Est. completion date: May 2014

Study information

• Verified date: May 2015
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: May 2014
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Cancer
• Solid Tumor

Intervention

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

Drug:
• Moxifloxacin
Administered orally
• Diphenhydramine
Administered IV

Locations

Country	Name	City	State
United States	ImClone Investigational Site	Ann Arbor	Michigan
United States	ImClone Investigational Site	Atlanta	Georgia
United States	ImClone Investigational Site	Houston	Texas
United States	ImClone Investigational Site	Metairie	Louisiana
United States	ImClone Investigational Site	Philadelphia	Pennsylvania
United States	ImClone Investigational Site	Providence	Rhode Island
United States	ImClone Investigational Site	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Secondary	Number of Participants With Drug-Related Adverse Events (AEs)	Data presented are the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade 3 or higher TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered to be related to ramucirumab. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events section.	Baseline up to data cut off (approximately 105.6 weeks)	Yes
Secondary	Maximum Concentration (Cmax) During Cycle 1	Maximum observed concentration of IMC-1121B (ramucirumab) in serum during Cycle 1 (1 cycle=21 days).	Cycle 1 [2.25 hours (h), 3.25 h, 4.25 h, 72 h, 168 h, 336 h postdose]	No
Secondary	Maximum Concentration (Cmax) During Cycle 1, Day 4	Cmax was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 3 for Cmax during Cycle 1.	Approximately Week 1 (Cycle 1, Day 4)	No
Secondary	Maximum Concentration (Cmax) During Cycle 1, Day 8	Cmax was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 3 for Cmax during Cycle 1.	Approximately Week 2 (Cycle 1, Day 8)	No
Secondary	Maximum Concentration (Cmax) During Cycle 1, Day 15	Cmax was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 3 for Cmax during Cycle 1.	Approximately Week 3 (Cycle 1, Day 15)	No
Secondary	Maximum Concentration (Cmax) During Cycle 2	Cmax was not calculated due to the sparse pharmacokinetic sampling employed on Cycle 2, Day 1.	Cycle 2 (predose and 1.25 hours postdose)	No
Secondary	Maximum Concentration (Cmax) During Cycle 3	The maximum observed serum concentration of IMC-1121B (ramucirumab) at steady state (Cmax,ss) during Cycle 3 (1 cycle=21 days).	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]	No
Secondary	Area Under Concentration (AUC) During Cycle 1	The area under the concentration versus time curve from time 0 to infinity [AUC(0-inf)] is reported during Cycle 1 (1 cycle=21 days).	Cycle 1 [2.25 hours (h), 3.25 h, 4.25 h, 72 h, 168 h, 336 h postdose]	No
Secondary	Area Under Concentration (AUC) During Cycle 1, Day 4	AUC was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 9 for AUC during Cycle 1 (Day 1 through Day 15).	Approximately Week 1 (Cycle 1, Day 4)	No
Secondary	Area Under Concentration (AUC) During Cycle 1, Day 8	AUC was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 9 for AUC during Cycle 1 (Day 1 through Day 15).	Approximately Week 2 (Cycle 1, Day 8)	No
Secondary	Area Under Concentration (AUC) During Cycle 1, Day 15	AUC was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 9 for AUC during Cycle 1 (Day 1 through Day 15).	Approximately Week 3 (Cycle 1, Day 15)	No
Secondary	Area Under Concentration (AUC) During Cycle 2, Day 1	AUC was not calculated due to the sparse pharmacokinetic sampling employed on Cycle 2, Day 1.	Approximately Week 1 (Cycle 2, Day 1)	No
Secondary	Area Under Concentration (AUC) During Cycle 3	The area under the concentration versus time curve over the dosing interval at steady state [AUC(tau,ss)] is reported during Cycle 3 (1 cycle=21 days).	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]	No