Clinical trial NCT00542958: Study of NK012 in Patients With Refractory Solid Tumors
Official title: A Phase I Dose-escalation Study of NK012 Administered Intravenously as a Single Dose Every Three Weeks in Patients With Refractory Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: Cancer
Refractory solid tumor
Lead sponsor: Nippon Kayaku Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2007-10-12
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Dose-limiting toxicity of NK012 in patients with UGT1A1*28 (wt/wt and wt/*28) genotype
timeFrame: At the end of Cycle 1 (each cycle is 21 days)
measure: Maximum tolerated dose of NK012 in patients with UGT1A1*28 (wt/wt and wt/*28) genotype
timeFrame: At the end of Cycle 1 (each cycle is 21 days)
measure: Recommended phase II dose of NK012 in patients with UGT1A1*28 (wt/wt and wt/*28) genotype
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
Secondary outcomes:
measure: Toxicity profile of NK012 in all patients
timeFrame: 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.
measure: Antitumor activity of NK012 according to RECIST criteria in all patients
timeFrame: 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.
measure: Pharmacokinetic parameter: Maximum concentration (Cmax)
timeFrame: 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.
measure: Pharmacokinetic parameter: Time to reach the maximum concentration (Tmax)
timeFrame: 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.
measure: Pharmacokinetic parameter: Terminal-phase half life (T1/2z)
timeFrame: 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.
measure: Pharmacokinetic parameter: Area under the concentration-time curve for time zero to infinity (AUCinf)
timeFrame: 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.
measure: Pharmacokinetic parameter: Total body clearance (CLtot)
timeFrame: 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.
measure: Pharmacokinetic parameter: Volume of distribution at steady-state (Vss)
timeFrame: 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.
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: SCRI Development Innovations, LLC
name: Howard A. Burris, III, MD
role: PRINCIPAL_INVESTIGATOR
References: