Clinical trial NCT01976143: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Metastatic Solid Tumors
Lead sponsor: Nektar Therapeutics
Sponsor class: INDUSTRY
First posted: 2013-11-05
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: QTcF interval values
timeFrame: Day -1 through Day 42
Secondary outcomes:
measure: Pharmacokinetics (PK) and ECG Parameters
timeFrame: Day 1 through Day 42
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: American Institute of Research, Los Angeles
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Cleveland
country: United States
facility: University Hospitals Case-Medical Center Seidman Cancer Center
state: Ohio
Study officials:
affiliation: Nektar Therapeutics
name: Ivan Gergel, MD
role: STUDY_DIRECTOR
References: