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

Phase 1

Completed

• Conditions: Solid Tumors
• Interventions: Drug: NKP-1339

• Registration Number: NCT01415297
• Lead Sponsor: Niiki Pharma Inc.

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.

Study Timeline

• Study Start: 2009-10
• Study First Submitted: 2011-08-03
• Study First Submitted QC: 2011-08-10
• Study First Posted: 2011-08-11
• Primary Completion: 2012-05
• Study Completion: 2016-01
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-18
• Last Update Posted: 2017-05-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NKP-1339	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Composite of pharmacokinetics	0, 0.25, 0.5, 1, 2, 4, 6, 10 and 24 hours	Plasma and urine samples will be analyzed to determine Cmax, Tmax, AUC, terminal elimination rate, elimination half-life, clearance,and volume of distribution.
To report any responses to NKP-1339 in subjects with advanced tumors	>8 weeks	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.
To explore pharmacodynamic endpoints which may be of use in the further development of NKP-1339	8 weeks	Transferrin, transferrin receptor and GRP-78 in plasma.

Trial Locations

Locations (2)

TGEN Clinical Research Services at Scottsdale Healthcare; 🇺🇸 Scottsdale, Arizona, United States

The Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States