Study of NK012 and 5-FU/LV in Solid Tumors Followed by Dose Expansion in Colorectal Cancer

November 12, 2014 updated by: Nippon Kayaku Co., Ltd.

A Phase I Study of NK012 in Combination With Infusional 5-fluorouracil and Leucovorin in Patients With Advanced Solid Tumors Followed by a Dose Expansion Phase in Patients With Metastatic Colorectal Cancer

The primary objective is to determine the maximum tolerated dose/recommended phase II dose of the combination regimen of NK012 and 5-fluorouracil in patients with advanced solid tumors.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

On Day 1 of each 28 day cycle, NK012 will be administered as a 30 minute IV infusion, followed by continuous infusion of 5-FU over 46 hours. On Day 15 of each cycle, patients again receive 5-FU continuous infusion. Treatment is expected to continue for 6 cycles, unless disease progression or the development of unacceptable toxicity requires discontinuation of the drug. At the discretion of the investigator, patients who show signs of benefit may continue beyond 6 cycles.

Once a MTD/RD has been determined for the combination regimen, a dose expansion cohort of patients with metastatic colorectal cancer will be treated at the determined MTD.

(Prior to Amendment 2, patients were receiving NK012 and 5-FU and leucovorin (LV). The dosing regimen was changed as of Amendment 2 to NK012 and 5-FU.)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
35

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States
        • Sarah Cannon Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Histologically or cytologically confirmed diagnosis of advanced solid tumor for which no efficacious therapy exists, or for which a camptothecin-based regimen would be appropriate.

  2. For the dose expansion at MTD/RD only:

    1. The patient must have failed oxaliplatin-based first line therapy for metastatic colorectal cancer. This includes patients who failed oxaliplatin-based therapy with progressive disease, as well as patients who, based on toxicity or MD/patient discretion, are no longer candidates for oxaliplatin. Patients who failed adjuvant therapy with oxaliplatin-based chemotherapy regimens within one year of last dose of oxaliplatin-based chemotherapy will also be considered eligible for this study.
    2. Patients must have had no more than one prior chemotherapy regimen in the metastatic setting. Patients who had radiosensitizing chemotherapy during radiation treatment will not have this treatment count as a prior chemotherapy regimen.
    3. Patients must have measurable disease by RECIST (version 1.1).
  3. Patient must have recovered from all acute adverse effects of prior therapies, excluding alopecia.
  4. For patients enrolled in the dose escalation phase, no more than 4 prior cytotoxic regimens in the metastatic setting.
  5. Prior irradiation to no more than 25% of the bone marrow.
  6. ECOG performance status of 0-1.
  7. Life expectancy of at least 12 weeks.
  8. Patients are at least 18 years of age.
  9. Adequate bone marrow function as defined by ANC ≥ 1500/mm^3 and platelet count ≥ 100,000/mm^3.
  10. AST and ALT ≤ 3.0 x ULN (5 x ULN if documented liver metastases) and total bilirubin ≤ 1.5 x ULN.

  11. Serum creatinine ≤ 1.5 x ULN, or creatinine clearance ≥ 60 mL/min by Cockcroft-Gault formula* for patients with serum creatinine > 1.5 x ULN.

    *Cockcroft-Gault formula for creatinine clearance (CrCl): Males: CrCl (ml/min) = (140 - age) x wt (kg) / (serum creatinine x 72) Females: Multiply the above result by 0.85

  12. Able to understand and show willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Prior chemotherapy, radiation therapy, or investigational therapy within 4 weeks (exception: 6 weeks for nitrosoureas or mitomycin C); or prior non-cytotoxic therapy within 5 drug half-lives (or 4 weeks, which ever is shorter); or monoclonal antibodies within 4 weeks prior to the first dose of study treatment.
  2. Concurrent use of other investigational agent.
  3. History of brain metastases or spinal cord compression, unless irradiated or treated a minimum of 4 weeks prior to first study treatment and stable without requirement of corticosteroids for > 1 week.
  4. Concurrent serious infections requiring parenteral antibiotic therapy.
  5. Pregnant or of childbearing potential and not using methods to avoid pregnancy. A negative pregnancy test must be documented at baseline for women of childbearing potential. Patients may not breast-feed infants while on this study.
  6. Significant cardiac disease including heart failure that meets NYHA class III and IV definitions, history of myocardial infarction within 6 months of study entry, uncontrolled dysrhythmias or poorly controlled angina.
  7. History of serious ventricular arrhythmia (VT or VF, ≥ 3 beats in a row), QTc ≥ 450 msec for men and 470 msec for women, or LVEF ≤ 40% by MUGA or ECHO.
  8. History of allergic reactions attributed to compounds of topoisomerase I inhibitors.
  9. Prior treatment with irinotecan.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment
Drug: NK012 and 5-FU
NK012 infusion on Day 1 of each 28 day cycle 5-FU continuous infusion on Days 1 and 15 of each 28 day cycle

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Number of patients with dose-limiting toxicity as determinant of the maximum tolerated dose/recommended dose
Time Frame: From date of first dose to off-study (or 30 days since last dose)
From date of first dose to off-study (or 30 days since last dose)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of patients with adverse events as a measure of safety and tolerability
Time Frame: From date of first dose to off-study (or 30 days since last dose)
From date of first dose to off-study (or 30 days since last dose)
Tumor measurements, as a measure of efficacy
Time Frame: Baseline, then every on average every 2 months until off-study
Efficacy, based on RECIST 1.1, will be assessed in all solid tumors, and in a specific subset of patients with colorectal cancer
Baseline, then every on average every 2 months until off-study
Area under the plasma concentration versus time curve (AUC) of NK012 and fluorouracil
Time Frame: 15,30min, 1,6,24,46.5,48,72hrs, Wk1,2,3,4 of cycle 1
15,30min, 1,6,24,46.5,48,72hrs, Wk1,2,3,4 of cycle 1
Peak Plasma Concentration (Cmax) of NK012 and fluorouracil
Time Frame: 15,30min, 1,6,24,46.5,72hrs, week 1,2,3,4 of cycle 1
15,30min, 1,6,24,46.5,72hrs, week 1,2,3,4 of cycle 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nippon Kayaku Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 2, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 9, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 11, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 13, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 12, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • A6012113US

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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