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

Phase 1

Completed

• Conditions: Advanced Cancer; Metastatic Solid Tumors
• Interventions: Drug: NKTR-102

• Registration Number: NCT01976143
• Lead Sponsor: Nektar Therapeutics

Brief 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

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 Timeline

• Study First Submitted: 2013-10-29
• Study First Submitted QC: 2013-10-29
• Study First Posted: 2013-11-05
• Study Start: 2014-02
• Primary Completion: 2016-06
• Study Completion: 2016-09
• Status Verified: 2016-12
• Last Update Submitted: 2016-12-20
• Last Update Posted: 2016-12-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NKTR-102	NKTR-102	A single 90 minute IV infusion of 220 mg/m2 NKTR-102

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (3)

American Institute of Research, Los Angeles; 🇺🇸 Los Angeles, California, United States

University Hospitals Case-Medical Center Seidman Cancer Center; 🇺🇸 Cleveland, Ohio, United States

UCSF Helen Diller Family Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States