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

Nektar Therapeutics

Status and phase: Completed; Phase 1

Conditions: Advanced or Metastatic Solid Tumors in Patients With Hepatic Impairment

Treatments: Drug: 120 mg/m2 NKTR 102; Drug: 145 mg/m2 NKTR 102; Drug: 50 mg/m2 NKTR 102

Study type: Interventional

Funder types: Industry

Identifiers

NCT01991678

12-102-13

Details and patient eligibility

About

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

Full description

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.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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25 participants in 3 patient groups

normal hepatic function

Experimental group

Description:

12 Patients will receive a 90-minute IV infusion

Treatment:

Drug: 145 mg/m2 NKTR 102

mild hepatic dysfunction

Experimental group

Description:

6 Patients will receive a 90-minute IV infusion

Treatment:

Drug: 120 mg/m2 NKTR 102

severe hepatic dysfunction

Experimental group

Description:

6 Patients will receive a 90-minute IV infusion

Treatment:

Drug: 50 mg/m2 NKTR 102