Clinical trial NCT00874731: A Study to Evaluate the Effect of MK-8669 (Ridaforolimus) on QTc Interval in Participants With Advanced Cancer (MK-8669-037)
Official title: A Clinical Trial to Assess the Effect of Ridaforolimus (AP23573; MK-8669) on QTc Interval in Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic or Locally Advanced Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-04-02
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess the potential for ridaforolimus to prolong the QTc interval (an effect on the electrical activity of the heart) in participants with advanced cancer. This study will be done in 2 parts. Part 1 (Pt 1) will evaluate the effect of a single 100 mg dose of ridaforolimus on QT interval in participants with advanced cancer. Fridericias's correction (QTcF) will be used. In Part 2 (Pt 2), participants will receive ridaforolimus at the current therapeutic dose (40 mg x 5 days).


Eligibility criteria: Inclusion Criteria:

* Participant must have metastatic or locally advanced cancer which has failed to respond to standard therapy or no therapy exists.
* If the participant is a female, she must be postmenopausal or if she is of childbearing potential she must have blood pregnancy tests during the study and be willing to use 2 methods of contraception.
* If the participant is male and has female partners of child-bearing potential, he must agree to use a medically acceptable method of contraception during the study and for 30 days after the last dose of study drug.

Exclusion Criteria:

* Participant has had chemotherapy, radiotherapy or biological therapy within the past 4 weeks.
* Participant is currently receiving other anti-cancer therapy.
* Participant is currently participating or has participated in a study with an investigation drug or device within the last 30 days.
* Participant has a primary central nervous system tumor or active brain metastases.
* Participant has a psychiatric disorder.
* Participant uses illegal drugs.
* Participant is pregnant or breastfeeding.
* Participant is known to be human immunodeficiency virus (HIV) positive.
* Participant has a known history of Hepatitis B or C.
* Participant has newly diagnosed diabetes.
* Participant has an active infection.
* Participant is unable to swallow capsules.
* Participant has received a blood transfusion with one week of study entry.
* Participant has a history of cardiac problems including heart failure, myocardial infarction, unstable angina, congestive heart failure or cardiac arrhythmia.
* Participant has a known sensitivity to the components of the study drug.
* Participant has not adequately recovered from any prior surgical procedure.
* Participant does not agree to refrain from use of herbal remedies and consumption of grapefruit juice for 2 weeks prior to and during the study.

Primary outcomes:
measure: Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 0.5 Hours
timeFrame: Baseline and 0.5 hours post-dose on Days 1 & 2 of Part 1
measure: Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 1 Hour
timeFrame: Baseline and 1 hour post-dose on Days 1 & 2 of Part 1
measure: Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 2 Hours
timeFrame: Baseline and 2 hours post-dose on Days 1 & 2 of Part 1
measure: Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 3 Hours
timeFrame: Baseline and 3 hours post-dose on Days 1 & 2 of Part 1
measure: Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 4 Hours
timeFrame: Baseline and 4 hours post-dose on Days 1 & 2 of Part 1
measure: Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 6 Hours
timeFrame: Baseline and 6 hours post-dose on Days 1 & 2 of Part 1
measure: Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 8 Hours
timeFrame: Baseline and 8 hours post-dose on Days 1 & 2 of Part 1
measure: Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 10 Hours
timeFrame: Baseline and 10 hours post-dose on Days 1 & 2 of Part 1
measure: Part 1. Mean Change From Baseline in Rate-Corrected (Fridericia's) QT Interval (QTcF) at 24 Hours
timeFrame: Baseline and 24 hours post-dose on Days 1 & 2 of Part 1
Secondary outcomes:
measure: Number of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to 7 months
measure: Number of Participants Discontinuing Study Treatment Due to an Adverse Event
timeFrame: Up to 6 months
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Lush RM, Patnaik A, Sullivan D, Papadopoulos KP, Trucksis M, McCrea J, Cerchio K, Li X, Stroh M, Selverian D, Orford K, Ebbinghaus S, Agrawal N, Iwamoto M, Wagner JA, Tolcher A. A single supratherapeutic dose of ridaforolimus does not prolong the QTc interval in patients with advanced cancer. Cancer Chemother Pharmacol. 2012 Oct;70(4):567-74. doi: 10.1007/s00280-012-1942-7. Epub 2012 Aug 10.