Antineoplastic Agents

All Drugs and Chemicals

Dabrafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

GSK2118436 (3 capsules of 75 mg) will be administered orally at the dose of 225 mg BID from Day 1 to 7 (and single dose on Day 8) under fasted conditions, either 1 hour before or 2 hours after a meal.

GSK2118436 (4 capsules of 75 mg) will be administered orally at the dose of 300 mg BID from Day 1 to 7 (and single dose on Day 8) under fasted conditions, either 1 hour before or 2 hours after a meal. If 225 mg BID is not tolerated in Part 1 /Cohort 1, then Part 1/Cohort 2 will not be initiated and 150 mg BID will be used in Part 2.

Subjects will receive a single dose of GSK2118436/placebo (4 capsules of 75 mg/highest tolerated dose) orally on the first 2 days of the study followed by 2 doses daily for 6 days and a single dose on the 9th day. There will be 1 day when a placebo will be given. All doses will be administered under fasted conditions, either 1 hour before or 2 hours after a meal.

Each capsule contains 75 mg of GSK2118436A as the mesylate salt, micronized particles as active equivalents.

GSK2118436 75 mg

Matching placebo capsules will be administered in Part 2 of the study.

Placebo

GSK Clinical Trials

This is a Phase I, multicenter, 2-part study with Part 1 designed as a safety lead-in and Part 2 designed to evaluate the effect of GSK2118436 on cardiac repolarization (corrected QT interval \[QTc\] duration) as compared with placebo in subjects with V600 BRAF mutation-positive tumors.

Each part of the study will consist of screening (14 days prior to the start of the study treatment), treatment and follow-up period (14 days).

In Part 1 in Cohort 1 six subjects will receive GSK2118436 225 mg twice a day (BID) on study days 1 to 7 and a single 225 milligram (mg) dose on morning of Day 8. Based on the safety data of subjects in Cohort 1 subjects will be enrolled in Cohort 2 and the dose of GSK2118436 will be escalated to 300 mg BID. If the 225 mg dose of GSK2118436 is not well tolerated in Cohort 1 (i.e., 2 or more dose-limiting toxicities \[DLTs\]), then Cohort 2 of Part 1 will not be initiated and a dose of 150 mg BID of GSK2118436 will be administered in Part 2 of the study. In Cohort 2 six subjects will receive GSK2118436 300 mg BID on Study Days 1 to 7 and a single 300 mg dose on the morning of Day 8. Based on the safety data of subjects in Cohort 2 subjects will be enrolled in Part 2. If the 300 mg BID dose level of GSK2118436 is not well tolerated, then the highest tolerated dose will be selected for Part 2 of the study.

In Part 1 of the study the decision to proceed to the next cohort or Part 2 of the study will be based on the safety data of at least 6 evaluable subjects (\<=1 DLTs during the 14 days following the first dose of GSK2118436).

In Part 2 of the study eligible subjects will receive a single dose of GSK2118436/placebo (4 capsules of 75 mg/highest tolerated dose) orally on the first 2 days of the study followed by 2 doses daily for 6 days and a single dose on the 9th day. There will be 1 day when a placebo will be given.

In both the parts of the study serial blood samples for pharmacokinetic (PK) analysis for GSK2118436 and its metabolites (GSK2285403, GSK2298683 and GSK2167542) will be obtained at the same time points on the first and last day of dosing (2nd day of dosing also included for Part 2). Safety electrocardiogram (ECG)s will be performed at several timepoints during the study. In Part 2 Holter ECG monitoring will be performed for 24 hours on the 1st, 2nd and 9th days of dosing.

A Study to Evaluate the Effect of Repeat Oral Dosing of GSK2118436 on Cardiac Repolarization in Subjects With V600 BRAF Mutation-Positive Tumors

A Two-Part Study to Evaluate the Effect of Repeat Oral Dosing of GSK2118436 on Cardiac Repolarization in Subjects With V600 BRAF Mutation-Positive Tumors: An Open-label, Dose-escalating Safety Lead-in Study Followed by a Single-sequence, Placebo-controlled, Single-blind Study

Safety and tolerability parameter will include a complete (head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen \[liver and spleen\], lymph nodes, extremities, height and weight) and brief (skin, lungs, cardiovascular system, abdomen \[liver and spleen\] and weight) physical examination at Baseline and at the end of Part 1 of the study.

Safety and tolerability parameter will include measurement of vital signs (recording of systolic and diastolic blood pressure, temperature, and pulse rate) at Baseline and at the end of Part 1 of the study.

Safety and tolerability parameter will include ECGs readings (heart rate and measurement of RR, PR, QRS, QT, and QTc intervals) at Baseline and at the end of Part 1 of the study.

Safety and tolerability parameter will include laboratory values (hematology, clinical chemistry, coagulation, liver function tests, cardiac enzyme and beta-hCG/serum or urine pregnancy test for female subjects of childbearing potential only) at Baseline and at end of Part 1 of the study.

Change from Baseline in QTcF interval at each time point for GSK2118436 will be calculated as average of 3 Holter ECG replicates per time point minus the value at Baseline.

Plasma concentrations of GSK2118436 and its metabolites GSK2285403, GSK2298683 and GSK2167542 will be recorded.

Pharmacokinetic data will include area under the time-concentration curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)) of GSK2118436 and its metabolites GSK2285403, GSK2298683 and GSK2167542.

Pharmacokinetic data will include maximum plasma concentration (Cmax) of GSK2118436 and its metabolites GSK2285403, GSK2298683 and GSK2167542.

Pharmacokinetic data will include predose concentration (Ctrough) of GSK2118436 and its metabolites GSK2285403, GSK2298683 and GSK2167542.

Pharmacokinetic data will include time of occurrence of Cmax (tmax) of GSK2118436 and its metabolites GSK2285403, GSK2298683 and GSK2167542.

The relationship between plasma concentrations of GSK2118436 and its metabolites (GSK2285403, GSK2298683 and GSK2167542) and the baseline-adjusted, placebo-corrected, time-matched change from Baseline in QTc intervals will be assessed.

ECG parameters: QT, QTcB, QTci, HR, RR interval, PR interval, QRS interval and morphology will be assessed in subjects receiving GSK2118436.

The plasma concentration of GSK2118436 and its metabolites GSK2285403, GSK2298683 and GSK2167542 will be measured.

Pharmacokinetic data will include AUC from time zero (pre-dose) to 10 hours after the last dose of study treatment (AUC(0-10)) and AUC(0 t) of GSK2118436 and its metabolites GSK2285403, GSK2298683 and GSK2167542.

Pharmacokinetic data will include AUC from time zero to infinity AUC(0-infinity) of GSK2118436 and its metabolites GSK2285403, GSK2298683 and GSK2167542 on Study Day 1, if data permit).

Pharmacokinetic data will include elimination half life (t1/2) of GSK2118436 and its metabolites GSK2285403, GSK2298683 and GSK2167542 if data permits.

Pharmacokinetic data will include C trough of GSK2118436 and its metabolites GSK2285403, GSK2298683 and GSK2167542.

Pharmacokinetic data will include Cmax of GSK2118436 and its metabolites GSK2285403, GSK2298683 and GSK2167542.

Pharmacokinetic data will include tmax of GSK2118436 and its metabolites GSK2285403, GSK2298683 and GSK2167542.

Safety parameters will include recording of AEs, in Part 2 of the study.

Safety parameters will include measurement of vital signs (recording of systolic and diastolic blood pressure, temperature, and pulse rate) at Baseline and at the end of Part 2 of the study.

Safety parameters will include ECGs readings (heart rate and measurement of RR, PR, QRS, QT, and QTc intervals) at Baseline and at the end of Part 2 of the study.

Safety parameters will include laboratory values (hematology, clinical chemistry, coagulation, liver function tests, cardiac enzyme and beta-hCG/serum or urine pregnancy test for female subjects of childbearing potential only) at Baseline and at end of Part 2 of the study.

GlaxoSmithKline

Tivozanib

1 x 1.5 mg capsule of tivozanib orally once daily for 21 days

tivozanib

Dennis Vargo, MD

The purpose of this study is to obtain QTc data, to assess the effects of tivozanib on ECG morphology, and to determine the pharmacokinetic pharmacodynamic (PK-PD) relationship between any observed changes in cardiac repolarization (defined by QTcF duration) and the serum concentration of tivozanib.

Tivozanib is a novel and potent pan-vascular endothelial growth factor (VEGF) receptor (VEGFR) tyrosine kinase inhibitor with potent activity against all 3 VEGFRs (VEGFR-1, -2, and -3). In nonclinical models and studies performed in humans, tivozanib has shown strong antiangiogenesis and antitumor activity.

This study is an open-label, non-randomized, exploratory single-arm trial evaluating the ECG and pharmacokinetic (PK)-ECG relationship, if any, of tivozanib in subjects with advanced solid tumors.

The purpose of this study is to evaluate the ECG intervals and morphology following treatment with tivozanib in subjects with advanced solid tumors and to determine the relationship, if any, of the change in QTc duration with serum concentration of tivozanib over time in subjects with advanced solid tumors.

A Cardiac Safety Study of Tivozanib to Evaluate the Electrocardiogram and Pharmacokinetic-Electrocardiogram Dynamics in Subjects With Advanced Solid Tumors

An Open-Label Cardiac Safety Study of Tivozanib to Evaluate the Electrocardiogram and Pharmacokinetic-Electrocardiogram Dynamics in Subjects With Advanced Solid Tumors

AVEO Pharmaceuticals, Inc.

480 mg/m2 by IV infusion over 30 minutes on Days 1, 8, and 15 of each 28-day cycle

480 mg/m2 30 min IV infusion on Days 1, 8, and 15 of a 28 day cycle

TH-302

Lee Cranmer, MD, PhD

The Primary objective of this study is:

1. To determine the cardiac safety of TH-302 in patients with advanced solid tumors

The Secondary objectives are:

1. To assess the pharmacokinetics (PK) of TH-302
2. To evaluate whether there is an association between plasma exposure to TH-302 and its active metabolite, Br-IPM, and effects on cardiac repolarization
3. To assess the safety and antitumor activity of TH-302 in patients with advanced solid tumors

This is an open-label study in patients with advanced solid tumors treated with TH-302 to assess safety, pharmacokinetics, and potential effects on cardiac repolarization and antitumor activity in patients with advanced solid tumors.

A dose of 480 mg/m2 of TH 302 will be administered by IV infusion over 30 minutes on Days 1, 8 and 15 of each 28-day cycle. Evaluations of safety, PK, and ECG parameters of cardiac repolarization will be performed on Study Day 1 and Day 2 of Cycle 1.

Cycles will be repeated every 28 days, until toxicity, progressive disease, patient or investigator decision to discontinue treatment, or until a maximum of six treatment cycles. Patients who are clearly benefitting from the treatment based on anti-cancer disease control and tolerability will be able to continue to receive drug past 6 cycles after discussion with the Sponsor. Tumor assessments will be performed after every 2 cycles during treatment.

The rationale for conducting this study is based on (a) prior data demonstrating the clinical benefit in advanced solid tumors as defined by tumor response or stable disease for at least 4 months, (b) tolerability of TH-302 at the proposed dose, and (c) a requirement to perform a dedicated ECG study to address the clinical evaluation of the potential for QT/QTc interval prolongation of TH-302.

A Cardiac Safety Study of TH-302 in Patients With Advanced Solid Tumors

Threshold Pharmaceuticals

Anti-Infective Agents

Anti-Allergic Agents

Antiemetics

Central Nervous System Depressants

Gastrointestinal Agents

Dermatologic Agents

Reproductive Control Agents

Antibodies

Antibodies, Monoclonal

Moxifloxacin

Immunoglobulins

Diphenhydramine

Promethazine

Ramucirumab

Norgestimate, ethinyl estradiol drug combination

Anti-Bacterial Agents

Hypnotics and Sedatives

Anesthetics

Anesthetics, Local

Histamine H1 Antagonists

Histamine

Histamine phosphate

Histamine Antagonists

Neurotransmitter Agents

Angiogenesis Inhibitors

Growth Inhibitors

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.

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

IMC-1121B

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)

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

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

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

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

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.

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.

Maximum observed concentration of IMC-1121B (ramucirumab) in serum during Cycle 1 (1 cycle=21 days).

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.

Cmax was not calculated due to the sparse pharmacokinetic sampling employed on Cycle 2, Day 1.

The maximum observed serum concentration of IMC-1121B (ramucirumab) at steady state (Cmax,ss) during Cycle 3 (1 cycle=21 days).

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).

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).

AUC was not calculated due to the sparse pharmacokinetic sampling employed on Cycle 2, Day 1.

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).

Eli Lilly and Company

Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.

Diphenhydramine: For Cycle 1 only, 25 to 50 milligrams (mg) diphenhydramine infused intravenously 1 day before ramucirumab therapy. For Cycles 1, 2, 3, and 4, 25 to 50 mg diphenhydramine infused intravenously 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.

Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.

IMC-1121B (Ramucirumab)

Between 18 and 65 years

>=65 years

Age, Customized

Sex: Female, Male

White

Black

Asian

Race/Ethnicity, Customized

United States

Region of Enrollment

Hispanic or Latino

Non-Hispanic or Latino

Ethnicity

Safety population: Participants who received any quantity of ramucirumab, regardless of their eligibility for the study.

Chief Medical Officer

Participants who received a full study dose of ramucirumab in Cycle 3 and had at least 1 pretreatment ECG and postinfusion ECG at scheduled times as specified in the protocol.

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

Related TEAE

Related SAE

Related Grade 3 or higher TEAE

Related AE leading to discontinuation

Safety population: participants who received any quantity of ramucirumab, regardless of their eligibility for the study.

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

Participants who received a full dose of ramucirumab and have evaluable Cmax data during Cycle 1.

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

Participants who received a full dose of ramucirumab and have evaluable Cmax data during Cycle 3.

Maximum Concentration (Cmax) During Cycle 3

Participants who received a full dose of ramucirumab and have evaluable AUC data during Cycle 1.

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

Ramucirumab: 10 milligrams/kilogram (mg/kg) infused intravenously over 1 hour, every 3 weeks (Day 1 of every 21-day cycle). Treatment continued for a minimum of 9 weeks without a break in between until there was evidence of disease progression or intolerable toxicity.

Diphenhydramine: 25 to 50 milligrams (mg) administered intravenously 1 day before each administration of ramucirumab for Cycles 1 to 4. For Cycle 5 and beyond, premedication with diphenhydramine was at the discretion of the investigator. Each participant was administered the same dose of diphenhydramine at all time points.

Moxifloxacin: The first 16 participants enrolled received a single dose of moxifloxacin (400 mg tablet orally by mouth) 1 week prior to being treated with ramucirumab.

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

Participants who received a full dose of ramucirumab and have evaluable AUC data during Cycle 3.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Evaluate the Effect of Repeat Oral Dosing of GSK2118436 on Cardiac Repolarization in Subjects With V600 BRAF Mutation-Positive Tumors	NCT01738451	Cancer	GSK2118436 75 m... Placebo	18 Years -	GlaxoSmithKline
A Cardiac Safety Study of Tivozanib to Evaluate the Electrocardiogram and Pharmacokinetic-Electrocardiogram Dynamics in Subjects With Advanced Solid Tumors	NCT01210846	Advanced Solid ...	tivozanib	18 Years -	AVEO Pharmaceuticals, Inc.
A Cardiac Safety Study of TH-302 in Patients With Advanced Solid Tumors	NCT02020226	Solid Tumors	TH-302	18 Years -	Threshold Pharmaceuticals
A Cardiac Safety Study of TH-302 in Patients With Advanced Solid Tumors	NCT02020226	Solid Tumors	TH-302	18 Years -	Threshold Pharmaceuticals
Study of Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes	NCT01017731	Cancer Solid Tumor	IMC-1121B Moxifloxacin Diphenhydramine	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for qtc

Every month we try and update this database with for qtc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for qtc

Every month we try and update this database with for qtc cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for qtc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.