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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Advanced Cancer, Metastatic Solid Tumors

Intervention / Treatment
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* Drug: NKTR-102


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NKTR-102<br>A single 90 minute IV infusion of 220 mg/m2 NKTR-102 | Drug: NKTR-102<br> <br> |

What is the study measuring?
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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 |