- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT01238939
Study of NK012 and 5-FU/LV in Solid Tumors Followed by Dose Expansion in Colorectal Cancer
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
Studieoversikt
Status
Intervensjon / Behandling
Detaljert beskrivelse
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.)
Studietype
Registrering (Forventet)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
-
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Tennessee
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Nashville, Tennessee, Forente stater
- Sarah Cannon Research Institute
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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.
- 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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Eksperimentell: Behandling
|
NK012 infusion on Day 1 of each 28 day cycle 5-FU continuous infusion on Days 1 and 15 of each 28 day cycle
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
---|---|
Antall pasienter med dosebegrensende toksisitet som determinant for maksimal tolerert dose/anbefalt dose
Tidsramme: Fra dato for første dose til off-studie (eller 30 dager siden siste dose)
|
Fra dato for første dose til off-studie (eller 30 dager siden siste dose)
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Antall pasienter med uønskede hendelser som mål på sikkerhet og tolerabilitet
Tidsramme: Fra dato for første dose til off-studie (eller 30 dager siden siste dose)
|
Fra dato for første dose til off-studie (eller 30 dager siden siste dose)
|
|
Tumor measurements, as a measure of efficacy
Tidsramme: 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
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Area under the plasma concentration versus time curve (AUC) of NK012 and fluorouracil
Tidsramme: 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
Tidsramme: 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
|
Samarbeidspartnere og etterforskere
Sponsor
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- A6012113US
Legemiddel- og utstyrsinformasjon, studiedokumenter
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