Advanced Cancer, Metastatic Solid Tumors
Conditions
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.
Interventions
DRUGNKTR-102
Sponsors
Nektar Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed