A Study in Cancer Patients to Evaluate the Effect of a Single Dose of NKTR-102 (Etirinotecan Pegol) on the QTc Interval and to Assess Pharmacokinetics and Safety

A Phase 1 Study to Evaluate the Effect of Nktr-102 for Injection (Etirinotecan Pegol) on the QT/QTC Interval in Patients With Advanced or Metastatic Solid Tumors

The purpose of this research study is to evaluate the effect of NKTR-102 on the QT/QTc interval in patients with advanced or metastatic solid tumors

Study Overview

• Status: Completed
• Conditions: Advanced Cancer; Metastatic Solid Tumors
• Intervention / Treatment: Drug: NKTR-102

Detailed Description

This is an open-label study that will assess the effect of NKTR- 102 on cardiac ventricular repolarization, as characterized by QTcF (QT interval with Fridericia correction) interval values, in patients with advanced or metastatic solid tumors following administration of a single dose of NKTR-102.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90017
      • American Institute of Research, Los Angeles
    • San Francisco, California, United States, 94143
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case-Medical Center Seidman Cancer 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:

• Advanced or metastatic solid tumor refractory to standard therapy
• Measurable or non-measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Resolution of acute toxic effects of prior chemotherapy and other cancer treatments
• Left ventricular ejection fraction (LVEF) ≥50% by echocardiogram
• Adequate bone morrow and organ function
• Electrolytes within normal limits
• Stopped tobacco use for 4 weeks prior to day 1 and during the study
• Agree to use adequate contraception

Exclusion Criteria:

• Previous anti-cancer therapy for malignancy within 4 weeks (6 weeks for the nitrosoureas or mitomycin C) before day 1
• Treatment with antiarrythmic drugs and any medication known to cause QTc prolongation within 4 weeks before screening and during the study
• Prior extensive anthracycline exposure
• Administration of cytochrome P450 CYP3A4 inducers and inhibitors within 4 weeks before day 1 and during the study
• Intake of grapefruit, grapefruit juice, Seville oranges, or other products containing grapefruit or Seville oranges within 14 days prior to day 1 and during the study
• History of serious cardiovascular disease
• Abnormal systolic blood pressure, diastolic blood pressure and/or heart rate
• History of additional risk factors for Torsade de Pointes
• Prolonged QTcF
• Important abnormalities of the ECG that may interfere with the interpretation of QTc interval changes at screening
• Implantable pacemaker or automatic implantable cardioverter defibrillator
• UGT1A1 genotype of TA 7 in both alleles (homozygous UGT1A1*28) or TA 8 in either one or both alleles (hetero- or homozygous for UGT1A1*37)
• Any major surgery within 4 weeks prior to day 1
• Concurrent treatment with other anticancer therapy
• Untreated central nervous system metastases
• Chronic or acute GI disorders resulting in diarrhea
• Pregnancy or lactation

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: NKTR-102; A single 90 minute IV infusion of 220 mg/m2 NKTR-102	Drug: NKTR-102

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QTcF interval values	10 pre-dose and 18 post-dose ECG measurements to evaluate the effect of NKTR-102	Day -1 through Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) and ECG Parameters	1 pre-dose and 18 post-dose blood samples to measure concentrations of NKTR-102 and its metabolites	Day 1 through Day 42

Collaborators and Investigators

• Sponsor: Nektar Therapeutics

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: October 29, 2013
• First Submitted That Met QC Criteria: October 29, 2013
• First Posted (Estimate): November 5, 2013

Study Record Updates

• Last Update Posted (Estimate): December 22, 2016
• Last Update Submitted That Met QC Criteria: December 20, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etirinotecan pegol
• Other Study ID Numbers: 12-102-12