A Study of Rovalpituzumab Tesirine to Study Cardiac Ventricular Repolarization in Subjects With Small Cell Lung Cancer

An Intensive QT/QTc Study to Investigate the Effects of Rovalpituzumab Tesirine on Cardiac Ventricular Repolarization in Subjects With Small Cell Lung Cancer

Study to evaluate the effect of rovalpituzumab tesirine on cardiac ventricular repolarization in subjects with small cell lung cancer (SCLC).

Study Overview

• Status: Completed
• Conditions: Small Cell Lung Carcinoma
• Intervention / Treatment: Drug: Rovalpituzumab Tesirine

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital-Cancer Centre
• United States
  • California
    • Los Angeles, California, United States, 90404
      • University of California Los Angeles
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute, Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Parkview Research Center
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Medical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed extensive-stage small-cell lung cancer (SCLC).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Adequate hematologic and organ function as confirmed by laboratory values

Exclusion Criteria:

• Clinically significant cardiac abnormalities including QRS duration of >120 msec; QTcF >470 msec for women and >450 msec for men; Abnormal cardiac rhythm; Clinically significant cardiac valve abnormality; Documented history of left ventricular ejection fraction <0.30 within 6 months; Permanent pacemaker or automatic implantable cardioverter defibrillator; History of torsades de pointes, congenital long QT syndrome, or family history of long QT syndrome or sudden death
• Recent or ongoing serious infection
• Women who are pregnant or breastfeeding
• Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, prior participation in a rovalpituzumab tesirine clinical trial, or known hypersensitivity to rovalpituzumab tesirine or excipient contained in the drug formulation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rovalpituzumab Tesirine; 0.3 mg/kg rovalpituzumab tesirine intravenously on Day 1 of every 6-week treatment cycle for 2 cycles omitting every third cycle	Drug: Rovalpituzumab Tesirine; Rovalpituzumab tesirine is a DLL3 targeted antibody drug conjugate (ADC); Other Names: SC16LD6.5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in QTcF interval from baseline QTcF following treatment with rovalpituzumab teserine as measured by extracting quantitative ECG parameters from ambulatory Holter monitors.	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in RR interval from baseline RR following treatment with rovalpituzumab teserine as measured by extracting quantitative ECG parameters from ambulatory Holter monitors.	12 weeks
Change in PR interval from baseline PR following treatment with rovalpituzumab teserine as measured by extracting quantitative ECG parameters from ambulatory Holter monitors.	12 weeks
Change in QRS duration interval from baseline QRS duration following treatment with rovalpituzumab teserine as measured by extracting quantitative ECG parameters from ambulatory Holter monitors.	12 weeks
Change in waveform composition interval from baseline waveform composition following treatment with rovalpituzumab teserine as measured by extracting quantitative ECG parameters from ambulatory Holter monitors.	12 weeks
Relationship between plasma rovalpituzumab tesirine concentration and change in QTcF interval from baseline.	12 weeks
Incidence of proarrhythmic adverse events stratified by change in QTcF from baseline of less than 10 ms or greater than 10 ms.	12 weeks
Incidence of adverse events.	From first dose through 30 days post-last-dose
Objective response rate	Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 24 months.
Duration of response	Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 24 months.
Progression free survival	Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 24 months.
Overall survival	Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 24 months.
Clinical benefit ratio	Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 24 months.
Maximum Plasma Concentration (Cmax)	Cycles 1 and 2: Day 1 (predose, 30 min, 2 and 4 hours postdose) and days 2,3,4,8,15,and 29; Cycles 4,5,7,8: Day 1 predose and 30 min postdose.
Area Under the Curve (AUC)	Cycles 1 and 2: Day 1 (predose, 30 min, 2 and 4 hours postdose) and days 2,3,4,8,15,and 29; Cycles 4,5,7,8: Day 1 predose and 30 min postdose.

Collaborators and Investigators

• Sponsor: Stemcentrx
• Investigators: Study Director: Daniel Da Costa, PharmD, AbbVie

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): September 12, 2018
• Study Completion (Actual): September 12, 2018

Study Registration Dates

• First Submitted: August 16, 2016
• First Submitted That Met QC Criteria: August 17, 2016
• First Posted (Estimate): August 22, 2016

Study Record Updates

• Last Update Posted (Actual): September 24, 2018
• Last Update Submitted That Met QC Criteria: September 20, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: SCRX001-007