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

Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01415297
• Other study ID #: NKP-1339-09-002
• Status: Completed
• Phase: Phase 1
• First received: August 3, 2011
• Last updated: May 18, 2017
• Start date: October 2009
• Est. completion date: January 2016

Study information

• Verified date: May 2017
• Source: Intezyne Technologies, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: January 2016
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Solid Tumors

Intervention

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.

Locations

Country	Name	City	State
United States	The Sarah Cannon Research Institute	Nashville	Tennessee
United States	TGEN Clinical Research Services at Scottsdale Healthcare	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Niiki Pharma Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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