Advanced Solid TumorsPhase 1NCT01238939
Study of NK012 and 5-FU/LV in Solid Tumors Followed by Dose Expansion in Colorectal Cancer
A Phase 1 study testing NK012 and 5-FU in people with Advanced Solid Tumors and Metastatic Colorectal Cancer, run by Nippon Kayaku Co., Ltd. at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Metastatic Colorectal Cancer
- What is being tested?
- NK012 and 5-FU
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2010to Mar 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- For the dose expansion at MTD/RD only:
- 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.
- 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.
- Patients must have measurable disease by RECIST (version 1.1).
- Patient must have recovered from all acute adverse effects of prior therapies, excluding alopecia.
Show all 16Show fewer
- For patients enrolled in the dose escalation phase, no more than 4 prior cytotoxic regimens in the metastatic setting.
- Prior irradiation to no more than 25% of the bone marrow.
- ECOG performance status of 0-1.
- Life expectancy of at least 12 weeks.
- Patients are at least 18 years of age.
- Adequate bone marrow function as defined by ANC ≥ 1500/mm^3 and platelet count ≥ 100,000/mm^3.
- AST and ALT ≤ 3.0 x ULN (5 x ULN if documented liver metastases) and total bilirubin ≤ 1.5 x ULN.
- 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
- Able to understand and show willingness to sign a written informed consent document.
Who cannot join
- 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.
- Concurrent use of other investigational agent.
- 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.
- Concurrent serious infections requiring parenteral antibiotic therapy.
- 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.
- 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.
Show all 9Show fewer
- 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.
- History of allergic reactions attributed to compounds of topoisomerase I inhibitors.
- Prior treatment with irinotecan.
Trial locations and contacts
1 site in 1 country.
United States1 site
Sarah Cannon Research Institute
Nashville, Tennessee
About this study
Official title: 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.
Read the 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.)
- Being tested
- NK012 and 5-FU
- Keywords
- solid tumors, colorectal cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NK012 and 5-FUDrug
NK012 infusion on Day 1 of each 28 day cycle 5-FU continuous infusion on Days 1 and 15 of each 28 day cycle
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Not described Receives: Drug: NK012 and 5-FU |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with dose-limiting toxicity as determinant of the maximum tolerated dose/recommended dose
Measured: From date of first dose to off-study (or 30 days since last dose)
Secondary outcomes (4)
Number of patients with adverse events as a measure of safety and tolerability
Measured: From date of first dose to off-study (or 30 days since last dose)
Tumor measurements, as a measure of efficacy
Efficacy, based on RECIST 1.1, will be assessed in all solid tumors, and in a specific subset of patients with colorectal cancer
Measured: Baseline, then every on average every 2 months until off-study
Area under the plasma concentration versus time curve (AUC) of NK012 and fluorouracil
Measured: 15,30min, 1,6,24,46.5,48,72hrs, Wk1,2,3,4 of cycle 1
Peak Plasma Concentration (Cmax) of NK012 and fluorouracil
Measured: 15,30min, 1,6,24,46.5,72hrs, week 1,2,3,4 of cycle 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2010 (estimated)
- Study startAug 2010
- Primary completionDec 2013
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nippon Kayaku Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01238939
- Sponsor's protocol ID
- A6012113US
- Status last verified
- Nov 2014
- First submitted
- 2 Nov 2010
- Last updated
- 13 Nov 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01238939
- Acronym / sponsor ID
- A6012113US
- Keywords
- solid tumors, colorectal cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Nippon Kayaku Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Aug 2010
- Primary completion
- Dec 2013 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 11 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: NK012 and 5-FU |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
- For the dose expansion at MTD/RD only:
- Patient must have recovered from all acute adverse effects of prior therapies, excluding alopecia.
- For patients enrolled in the dose escalation phase, no more than 4 prior cytotoxic regimens in the metastatic setting.
- Prior irradiation to no more than 25% of the bone marrow.
Key exclusion criteria (9 listed)
- 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.
- Concurrent use of other investigational agent.
- 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.
- Concurrent serious infections requiring parenteral antibiotic therapy.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NK012 and 5-FUNK012 infusion on Day 1 of each 28 day cycle 5-FU continuous infusion on Days 1 and 15 of each 28 day cycle | Drug | Treatment |
Primary outcome
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)
4 secondary outcomes
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)
Tumor measurements, as a measure of efficacy
Time frame: 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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2014.
Related trials for Advanced Solid Tumors
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NK012 and 5-FU in people with Advanced Solid Tumors and Metastatic Colorectal Cancer, run by Nippon Kayaku Co., Ltd. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2014; AzTrials last refreshed its copy on 6 Nov 2026.