Dose Escalation Study of NKP-1339 to Treat Advanced Solid Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: NKP-1339

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • TGen Clinical Research Services at Scottsdale Healthcare
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NKP-1339; NKP-1339 will be administered in single patient cohorts until ≥ Grade 2 toxicity encountered, at which time cohorts converted to a standard 3 + 3 dose escalation scheme. When MTD is reached, an expanded cohort of up to 25 patients will be enrolled at the MTD.	Drug: NKP-1339; NKP-1339 is administered as a 30-90 minute IV infusion (based on volume to be infused) on days 1, 8, and 15 of a 28 day cycle.; Other Names: IT-139

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with related adverse events	The incidence and severity of related adverse events and laboratory abnormalities will be used to assess the safety and tolerability of NKP-1339.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of pharmacokinetics	Plasma and urine samples will be analyzed to determine Cmax, Tmax, AUC, terminal elimination rate, elimination half-life, clearance,and volume of distribution.	0, 0.25, 0.5, 1, 2, 4, 6, 10 and 24 hours
To report any responses to NKP-1339 in subjects with advanced tumors	Tumor assessments every 2 cycles if patients continue treatment beyond 2 Cycles. Treatment is allowed beyond 2 cycles in patients who achieved at least stable disease, at the discretion of investigator and consent of the patient.	>8 weeks
To explore pharmacodynamic endpoints which may be of use in the further development of NKP-1339	Transferrin, transferrin receptor and GRP-78 in plasma.	8 weeks

Collaborators and Investigators

• Sponsor: Niiki Pharma Inc.
• Investigators: Principal Investigator: Daniel D. Von Hoff, MD, TGen Clinical Research Services at Scottsdale Healthcare; Principal Investigator: Howard A. Burris, III, MD, The Sarah Cannon Research Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2009
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: August 3, 2011
• First Submitted That Met QC Criteria: August 10, 2011
• First Posted (Estimate): August 11, 2011

Study Record Updates

• Last Update Posted (Actual): May 19, 2017
• Last Update Submitted That Met QC Criteria: May 18, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Phase 1; advanced solid tumors
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NKP-1339-09-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided