Study of NK012 in Patients With Refractory Solid Tumors

NCT00542958 | Completed Phase 1

• 1 other identifier: N06-10089
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Cancer

Keywords

Cancer; Refractory solid tumor

Outcome Measures

Primary Outcomes (3)

• 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)

• 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)

• 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 Outcomes (8)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (1)

NK012

EXPERIMENTAL

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.

Drug: NK012

Interventions

NK012 DRUG

9.0, 12.0, 16.0, 21.0, 28.0 mg/m\^2, and to be determined. Intravenous infusion

NK012

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nippon Kayaku Co., Ltd.: lead

Study Sites (1)

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Neoplasms

Study Officials

• Howard A. Burris, III, MD

  SCRI Development Innovations, LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2007
• First Posted: October 12, 2007
• Study Start: March 1, 2007
• Primary Completion: April 1, 2008
• Study Completion: December 1, 2011
• Last Updated: October 28, 2019

Record last verified: 2013-03

Locations

US (1)