A Study in Cancer Patients With Hepatic Impairment to Evaluate the Pharmacokinetics and Safety of NKTR-102 (Etirinotecan Pegol)

Study Overview
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Brief Summary
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The purpose of this study is to investigate the PK and safety of NKTR-102 in patients with mild, moderate, or severe hepatic impairment.

Detailed Description
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Safety and PK data from patients with mild, moderate, or severe hepatic impairment will be compared with a control group consisting of patients with normal hepatic function.

Official Title
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An Open-Label, Parallel-Group, Multicenter, Phase 1 Study to Investigate the Pharmacokinetics of NKTR-102 for Injection (Etirinotecan Pegol) in Patients With Advanced or Metastatic Solid Tumors and Hepatic Impairment

Conditions
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Advanced or Metastatic Solid Tumors in Patients With Hepatic Impairment

Intervention / Treatment
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* Drug: 145 mg/m2 NKTR 102
* Drug: 120 mg/m2 NKTR 102
* Drug: 50 mg/m2 NKTR 102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or progressive advanced solid tumor malignancies Measurable or non-measurable disease Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Life expectancy greater than 3 months Resolution of all acute toxic effects of prior chemotherapy, and other cancer treatments Adequate bone morrow and kidney function No signs of decompensated liver cirrhosis or ascites requiring therapeutic paracentesis Agree to use adequate contraception Exclusion Criteria: Previous chemotherapy, immunotherapy, chemo-embolization, targeted therapy or investigational agent for malignancy within 4 weeks prior to day 1 Cytochrome P450 CYP3A4 inducers and inhibitors within 4 weeks prior to day 1 Intake of grapefruit, grapefruit juice, Seville oranges, or other products containing grapefruit or Seville oranges within 14 days prior to day 1 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) Major surgery within 4 weeks prior to day 1 Undergone a liver or other organ transplant Concurrent treatment with other anti-cancer therapy Untreated central nervous system metastases Ongoing or active infection 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: normal hepatic function<br>12 Patients will receive a 90-minute IV infusion | Drug: 145 mg/m2 NKTR 102<br> <br> |
| Experimental: mild hepatic dysfunction<br>6 Patients will receive a 90-minute IV infusion | Drug: 120 mg/m2 NKTR 102<br> <br> |
| Experimental: severe hepatic dysfunction<br>6 Patients will receive a 90-minute IV infusion | Drug: 50 mg/m2 NKTR 102<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of NKTR-102 and its metabolites | 1 pre-dose PK measurements 14 post-dose PK measurements | Day 1 through Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of NKTR-102 | Assessments are: physical examinations, vital signs, ECGs, AEs, and laboratory testing. | Day 1 through Day 42 |