Clinical trial NCT01415297: Dose Escalation Study of NKP-1339 to Treat Advanced Solid Tumors
Official title: A Phase I Dose Escalation Study of NKP-1339 Administered on Days 1, 8 and 15 of Each 28-Day Cycle in Patients With Advanced Solid Tumors Refractory to Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Phase 1
advanced solid tumors
Lead sponsor: Intezyne Technologies, Inc.
Sponsor class: INDUSTRY
First posted: 2011-08-11
Enrollment: 46
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 study is to determine the safety and maximal tolerated dose of NKP-1339, a ruthenium containing compound administered intravenously on a weekly schedule, in patients with advanced solid tumors. The responses to treatment in this population will be evaluated. In addition, the PD and PK properties of the compound will be explored.

Detailed description: NKP-1339 is a novel GRP78 targeted ruthenium based anti-cancer compound which is intravenously administered. GRP78 is a key regulator of misfolded protein processing, which is unregulated in cancer cells. In nonclinical anti-tumor studies, NKP-1339 showed activity against many tumor types, including those resistant to platinum and other standard anti-cancer agents. This Phase I trial evaluates the safety, tolerability, maximum tolerated dose, pharmacokinetics, and pharmacodynamics of NKP-1339.

Eligibility criteria: Inclusion Criteria:

* Patients ≥ 18 years with histologically or cytologically confirmed advanced solid tumors refractory to standard therapies who have signed an IRB approved Informed Consent Form (ICF).
* ECOG PS 0 or 1.
* Adequate hematologic, hepatic and renal function
* Minimum life expectancy ≥ 12 weeks

Exclusion Criteria:

* No supplemental Iron, i.e., therapeutic or as part of a multivitamin regimen.
* No chemotherapy, immunotherapy, or radiotherapy for \< 4 weeks, BMTs \< 9 months or major surgery \< 3 weeks.
* No symptomatic central nervous system metastases. No primary brain tumors or known brain metastasis unless clinically stable and on stable or reducing dose of steroids.
* No evidence of ischemia, MI within the past 6 months, or other significant abnormality on ECG.
* No clinically significant active infection including HIV, hepatitis B, or hepatitis C.
* No Peripheral neuropathy ≥ Grade 2

Primary outcomes:
measure: Number of participants with related adverse events
timeFrame: 8 weeks
Secondary outcomes:
measure: Composite of pharmacokinetics
timeFrame: 0, 0.25, 0.5, 1, 2, 4, 6, 10 and 24 hours
measure: To report any responses to NKP-1339 in subjects with advanced tumors
timeFrame: >8 weeks
measure: To explore pharmacodynamic endpoints which may be of use in the further development of NKP-1339
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: TGEN Clinical Research Services at Scottsdale Healthcare
state: Arizona
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: TGEN Clinical Research Services at Scottsdale Healthcare
name: Daniel D. Von Hoff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Sarah Cannon Research Institute
name: Howard A. Burris, III, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Burris HA, Bakewell S, Bendell JC, Infante J, Jones SF, Spigel DR, Weiss GJ, Ramanathan RK, Ogden A, Von Hoff D. Safety and activity of IT-139, a ruthenium-based compound, in patients with advanced solid tumours: a first-in-human, open-label, dose-escalation phase I study with expansion cohort. ESMO Open. 2017 Feb 23;1(6):e000154. doi: 10.1136/esmoopen-2016-000154. eCollection 2016.