Study of NK012 in Patients With Refractory Solid Tumors

Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00542958
• Other study ID #: N06-10089
• Status: Completed
• Phase: Phase 1
• Start date: March 2007
• Est. completion date: December 2011

Study information

• Verified date: March 2013
• Source: Nippon Kayaku Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether NK012 is safe and effective in the treatment of refractory solid tumors

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 information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: December 2011
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• NK012
9.0, 12.0, 16.0, 21.0, 28.0 mg/m^2, and to be determined. Intravenous infusion

Locations

Country	Name	City	State
United States	Sarah Cannon Research Institute	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Nippon Kayaku Co., Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	Recommended phase II dose of NK012 in patients with UGT1A1*28 (wt/wt and wt/*28) genotype	After MTD was determined, the administration schedule was changed to every 28 days per cycle, considering patient safety.	At the end of Cycle 1 (each cycle is 28 days)
Secondary	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.
Secondary	Antitumor activity of NK012 according to RECIST criteria in all patients	Overall response will be evaluated every 2 cycles	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.