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Effect of SAR302503 on ECG Activity in Patients With Solid Tumors

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ClinicalTrials.gov Identifier: NCT01836705
Recruitment Status : Completed
First Posted : April 22, 2013
Last Update Posted : June 4, 2014
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE April 17, 2013
First Posted Date  ICMJE April 22, 2013
Last Update Posted Date June 4, 2014
Study Start Date  ICMJE May 2013
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 17, 2013)
QTc Friderica (QTcF) parameter [ Time Frame: 16 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2013)
  • Electrocardiographic parameters (Heart Rate) [ Time Frame: 16 days ]
  • Electrocardiographic parameters (QT) [ Time Frame: 16 days ]
  • Electrocardiographic parameters (QTcBazett) [ Time Frame: 16 days ]
  • Electrocardiographic parameters (QTcN) [ Time Frame: 16 days ]
  • Electrocardiographic parameters (PR interval) [ Time Frame: 16 days ]
  • Electrocardiographic parameters (QRS interval) [ Time Frame: 16 days ]
  • Anti-tumor activity [ Time Frame: 16 or more days ]
  • Number of participants with Adverse Events [ Time Frame: 16 or more days ]
  • Pharmacokinetic parameter: Cmax, AUC0-24, Tmax, Tmax, Ctrough [ Time Frame: 16 days ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of SAR302503 on ECG Activity in Patients With Solid Tumors
Official Title  ICMJE Effect of 14-day Repeated Oral Doses of SAR302503 on Ventricular Repolarization, Compared to 1-day Placebo in Adult Patients With Refractory Solid Tumors
Brief Summary

Primary Objective:

- To assess the effect of SAR302503 (500 mg) administered as 14-day repeated doses on the QTcF interval compared to 1-day placebo in patients with advanced solid tumors.

Secondary Objectives:

  • To assess the effect of SAR302503 administered as 14-day repeated doses on heart rate (HR), QT, QTcB, and QTcN, PR and QRS compared to placebo.
  • To assess the clinical and laboratory safety of SAR302503
  • To document the plasma concentrations of SAR302503 at the time of ECG investigation.
  • To explore the Pharmacokinetic/Pharmacodynamic relationship between SAR302503 concentration and QTcF
  • To explore antitumor activity
Detailed Description Total 7-10 weeks if not progressing to Segment 2. Segment 2 will be additional in 28-day cycles.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Neoplasm Malignant
Intervention  ICMJE
  • Drug: SAR302503 (TG101348)

    Pharmaceutical form:capsule

    Route of administration: oral

  • Drug: Placebo SAR302503

    Pharmaceutical form:capsule

    Route of administration: oral

  • Drug: Panolosetron

    Pharmaceutical form:solution

    Route of administration: intravenous

    Other Name: Aloxi®
Study Arms  ICMJE Experimental: Single-sequence
SAR302503 Placebo (1 day)-SAR302503 (500 mg, oral, qd, 14 days)
Interventions:
  • Drug: SAR302503 (TG101348)
  • Drug: Placebo SAR302503
  • Drug: Panolosetron
Publications * Ogasawara K, Xu C, Yin J, Darpo B, Carayannopoulos L, Xue H, Palmisano M, Krishna G. Evaluation of the Potential for QTc Prolongation With Repeated Oral Doses of Fedratinib in Patients With Advanced Solid Tumors. Clin Pharmacol Drug Dev. 2021 Apr;10(4):366-375. doi: 10.1002/cpdd.850. Epub 2020 Jul 16.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 3, 2014)
60
Original Estimated Enrollment  ICMJE
 (submitted: April 17, 2013)
50
Actual Study Completion Date  ICMJE May 2014
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria :

- Histologically or cytologically confirmed advanced solid malignancy that is metastatic or unresectable, and for which standard curative measures do not exist

Exclusion criteria:

  • Prior history of torsades de pointe, or congenital long QT syndrome.
  • Conditions with screening ECG in which repolarization is difficult to interpret, or showing significant abnormalities. This includes, but is not limited to: High degree atrioventricular (AV) block, pacemaker, atrial fibrillation or flutter
  • Screening ECG with QTc B or QTc F ≥480 msec (within 8 days of Day-1)
  • Significant hypokalemia at screening (K+ <3.5 mmol/L) (within 8 days of Day-1)
  • Significant hypomagnesemia at screening and inclusion (Mg++ <0.7 mmol/L) (within 8 days of Day -1)
  • Patient receives (and cannot discontinue), or is scheduled to receive, a concomitant treatment known to carry a risk of both QT prolongation and torsade de pointe for 2 weeks before Day 1 and for the duration of Segment 1
  • Absence of completion of all prior chemotherapy, biological therapy, hormonal therapy, targeted non-cytotoxic therapy ≥3 weeks; and radiotherapy ≥2 weeks prior to inclusion.
  • Patients with uncontrolled brain metastases or primary brain tumor. Patients with brain metastasis are considered eligible if the patient has not received radiation therapy for brain metastasis within 2 weeks of enrollment and has been on a stable dose of steroids for ≥ 2 weeks.
  • Participation in any study of an investigational agent (drug, biologic, device) within 30 days prior to initiation of study drug, unless during non-treatment phase.
  • Anticipation of need for a major surgical procedure or radiation therapy during the study treatment.
  • Concurrent treatment in another clinical trial or with any other cancer therapy including chemotherapy, biological therapy, hormonal therapy, radiotherapy, chemoembolization, cryotherapy, targeted non-cytotoxic therapy or patients planning to receive these treatments during the study.
  • Inadequate organ function as defined by:
  • Absolute neutrophil count (ANC) <1.5 X 10^9/L
  • Platelet count <100 X 10^9/L
  • Hemoglobin: <9 g/dL
  • Serum creatinine >1.5 x the upper limit of normal (ULN)
  • Serum amylase or lipase >1.5 x ULN
  • Total bilirubin >1.5 x ULN
  • Aspartate aminotransferase or alanine aminotransferase ≥2.5 x ULN
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) >2 at study entry.
  • Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.
  • Ongoing or recent history (within 3 months of Day 1 Segment 1) of clinically significant dysrrhythmia.
  • Patients taking a beta blocker within 7 days to Day 1 Segment 1 and during Segment 1
  • Other concurrent serious illness or medical condition, including active infection or HIV disease.
  • Patients with known active (acute or chronic) Hepatitis A, B, C, and hepatitis B and or C carriers. Prior history of chronic liver disease.
  • Patients with history of partial or total gastrectomy, or, if in the opinion of the investigator, have any other disorder that would inhibit absorption of oral medications.
  • Any severe acute or chronic medical, neurological, or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with interpretation of study results and, in the Investigator's opinion, would make the patient inappropriate for entry into this study.
  • Contra-indications for palonosetron.
  • Use of drugs or herbal agents known to be at least moderate inhibitors or inducers of CYP3A4, sensitive CYP3A4 substrate, or CYP3A4 substrate with narrow therapeutic index, within 2 weeks of Day 1 and during study.
  • Concomitant treatment with H2-blockers is not allowed within 7 days prior to Day 1 Segment 1 and during entire study.
  • Known hypersensitivity to any excipients in IMP formulations.
  • Pregnant or lactating females
  • Women of childbearing potential, unless using effective contraception (other than oral contraceptives) while on study drug. Men who partner with a woman of childbearing potential, unless they agree to use effective contraception while on study drug

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01836705
Other Study ID Numbers  ICMJE TES13519
2012-005642-38 ( EudraCT Number )
U1111-1115-7323 ( Other Identifier: UTN )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP