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

Sponsor

Niiki Pharma Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01415297

Collaborator

(none)

Enrollment

Locations

Arm

Actual Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: NKP-1339	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

46 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

May 1, 2012

Actual Study Completion Date :

Jan 1, 2016

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	TGEN Clinical Research Services at Scottsdale Healthcare	Scottsdale	Arizona	United States	85258
2	The Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203

Sponsors and Collaborators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Niiki Pharma Inc.

ClinicalTrials.gov Identifier:

NCT01415297

Other Study ID Numbers:

NKP-1339-09-002

First Posted:

Aug 11, 2011

Last Update Posted:

May 19, 2017

Last Verified:

May 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Keywords provided by Niiki Pharma Inc.

Phase 1

advanced solid tumors

Additional relevant MeSH terms:

Neoplasms

Study Results

No Results Posted as of May 19, 2017