Study of NK012 in Patients With Refractory Solid Tumors
- Registration Number
- NCT00542958
- Lead Sponsor
- Nippon Kayaku Co., Ltd.
- Brief Summary
The purpose of this study is to determine whether NK012 is safe and effective in the treatment of refractory solid tumors
- Detailed Description
This is a Phase I dose-escalation study of the intravenous administration of NK012 in patients with refractory solid tumors. Patients will receive NK012 as an intravenous infusion over 30 minutes on Day 1 followed by a 20-day observation period for a total of 21 days (3 weeks) per cycle. Two patient populations will be evaluated separately: patients with UGT1A1\*28 genotype homozygous wild type (wt/wt) and heterozygous (wt/\*28) variants as one group, and patients with UGT1A1\*28 homozygous variant (\*28/\*28) as another group.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 39
Inclusion Criteria
- Histologically confirmed malignant solid tumor for which there are no known regimens or protocol treatments of higher efficacy or priority
- Failed conventional therapy for the cancer or have a malignancy for which a conventional therapy does not exist
- Recovered from all acute adverse effects of prior therapies, excluding alopecia (hair loss)
- Life expectancy of at least 12 weeks and an EOCG performance status of 0 or 1
- 18 years of age or older
- Adequate kidney, liver, and bone marrow function
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria
- Have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or have not recovered from adverse effects due to agents administered more than 4 weeks earlier
- Receiving any other investigational agent
- History of brain metastases or spinal cord compression, unless irradiated a minimum of 4 weeks before study entry and stable without requirement for corticosteroids for > 1 week
- History of allergic reactions attributed to compounds of similar chemical composition to NK012
- Concurrent serious infections (i.e., requiring an intravenous antibiotic)
- Pregnant women or women of childbearing potential who are not using methods to avoid pregnancy; a negative pregnancy test (urine or serum) must be documented at baseline and before every NK012 administration for women of childbearing potential; no breast-feeding while on study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris or psychiatric illness/social situations that would limit compliance with study requirements
- Significant cardiac disease
- History of serious ventricular arrhythmia
- Positive for anti-HbsAg, anti-HCV, anti-HIV, or anti-syphilis antibodies
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description NK012 NK012 This is a Phase I dose-escalation study of the intravenous administration of NK012 in patients with refractory solid tumors. Patients will receive NK012 as an intravenous infusion over 30 minutes on Day 1 followed by a 20-day observation period for a total of 21 days (3 weeks) per cycle. Two patient populations will be evaluated separately: patients with UGT1A1\*28 genotype homozygous wild type (wt/wt) and heterozygous (wt/\*28) variants as one group, and patients with UGT1A1\*28 homozygous variant (\*28/\*28) as another group. Dose-escalation in each patient population will proceed according to the predefined dose level. For UGT1A1\*28 (wt/wt and wt/\*28) patients, at least 3 evaluable patients will be treated at each dose level. UGT1A1 homozygous (\*28/\*28) patients will be treated at 50% of the current dose level. Patients will receive up to 6 cycles of NK012, unless they experience unacceptable toxicity or disease progression, requiring withdrawal from the study.
- Primary Outcome Measures
Name Time Method Maximum tolerated dose of NK012 in patients with UGT1A1*28 (wt/wt and wt/*28) genotype At the end of Cycle 1 (each cycle is 21 days) Dose-limiting toxicity of NK012 in patients with UGT1A1*28 (wt/wt and wt/*28) genotype At the end of Cycle 1 (each cycle is 21 days) Recommended phase II dose of NK012 in patients with UGT1A1*28 (wt/wt and wt/*28) genotype At the end of Cycle 1 (each cycle is 28 days) After MTD was determined, the administration schedule was changed to every 28 days per cycle, considering patient safety.
- Secondary Outcome Measures
Name Time Method Pharmacokinetic parameter: Time to reach the maximum concentration (Tmax) Sampling during Cycle 1 (first 3 weeks) and up to Day 3 of Cycle 2, if applicable, total 24 days for 21-days cycle or 31 days for 28-day cycle. Toxicity profile of NK012 in all patients Through study completion (6 cycles of study drug administration period and 30 days of follow-up period), an average of 5 months for 21-day cycle or 6 months for 28-days cycle. Pharmacokinetic parameter: Terminal-phase half life (T1/2z) Sampling during Cycle 1 (first 3 weeks) and up to Day 3 of Cycle 2, if applicable, total 24 days for 21-days cycle or 31 days for 28-day cycle. Pharmacokinetic parameter: Area under the concentration-time curve for time zero to infinity (AUCinf) Sampling during Cycle 1 (first 3 weeks) and up to Day 3 of Cycle 2, if applicable, total 24 days for 21-days cycle or 31 days for 28-day cycle. Pharmacokinetic parameter: Total body clearance (CLtot) Sampling during Cycle 1 (first 3 weeks) and up to Day 3 of Cycle 2, if applicable, total 24 days for 21-days cycle or 31 days for 28-day cycle. Pharmacokinetic parameter: Volume of distribution at steady-state (Vss) Sampling during Cycle 1 (first 3 weeks) and up to Day 3 of Cycle 2, if applicable, total 24 days for 21-days cycle or 31 days for 28-day cycle. Antitumor activity of NK012 according to RECIST criteria in all patients Through study completion (6 cycles of study drug administration period and 30 days of follow-up period), an average of 5 months for 21-day cycle or 6 months for 28-days cycle. Overall response will be evaluated every 2 cycles
Pharmacokinetic parameter: Maximum concentration (Cmax) Sampling during Cycle 1 (first 3 weeks) and up to Day 3 of Cycle 2, if applicable, total 24 days for 21-days cycle or 31 days for 28-day cycle.
Trial Locations
- Locations (1)
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States