Solid Tumors
Conditions
Keywords
Phase 1, advanced solid tumors
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.
Interventions
DRUGNKP-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.
Sponsors
Niiki Pharma Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed