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

Advanced Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01976143
• Other study ID #: 12-102-12
• Status: Completed
• Phase: Phase 1
• First received: October 29, 2013
• Last updated: December 20, 2016
• Start date: February 2014
• Est. completion date: September 2016

Study information

• Verified date: December 2016
• Source: Nektar Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: September 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Cancer
• Metastatic Solid Tumors

Intervention

Drug:
• NKTR-102

Locations

Country	Name	City	State
United States	University Hospitals Case-Medical Center Seidman Cancer Center	Cleveland	Ohio
United States	American Institute of Research, Los Angeles	Los Angeles	California
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Nektar Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	QTcF interval values	10 pre-dose and 18 post-dose ECG measurements to evaluate the effect of NKTR-102	Day -1 through Day 42	Yes
Secondary	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	No