- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00520091
Irinotecan, Cisplatin, and Radiation Therapy With or Without Celecoxib in Treating Patients With Stage II, Stage III, or Stage IV Esophageal Cancer
A Pilot Study of the Biologic Efficacy and Safety of the Addition of Celecoxib to a Program of Induction Chemotherapy and Neo-Adjuvant Chemo-Radiotherapy for the Treatment of Esophageal Cancer
RATIONALE: Drugs used in chemotherapy, such as irinotecan and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy and radiation therapy together with celecoxib may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving irinotecan and cisplatin together with radiation therapy with or without celecoxib works in treating patients with stage II, stage III, or stage IV esophageal cancer.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
OBJECTIVES:
Primary
- To measure the rates of cellular apoptosis and proliferation at baseline and during chemoradiotherapy with and without celecoxib using biopsy samples from patients with stage II, III, or IV esophageal cancer.
- To determine if an acceptable rate of pathologic complete remission can be achieved in a subset of patients with potentially resectable esophageal cancer.
Secondary
- To assess the safety of the addition of daily celecoxib to chemoradiotherapy.
- To estimate the median overall survival in a subset of patients with resectable disease.
- To quantitate expression of cyclooxygenase (COX)-2 and formation of prostaglandin E2 (PGE2) in patients with esophageal cancer.
- To assess the ability of celecoxib to decrease formation of PGE2 in tumor tissue by measuring pre- and post-treatment tumor concentrations of PGE2.
- To quantitate downstream effects of inhibition of COX-2 function in the setting of treatment with chemotherapy.
- To measure the radiographic response rate in patients with unresectable esophageal cancer.
OUTLINE: This is a multicenter study. Patients are sequentially enrolled into 1 of 2 treatment groups.
- Group 1: Patients receive cisplatin IV over 1 hour and irinotecan hydrochloride IV over 90 minutes on days 1, 8, 22, 29, 43, 50, 64, and 71. Patients also undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 43.
- Group 2: Patients receive chemoradiotherapy as in group 1. Patients also receive oral celecoxib twice daily beginning 3 days before the initiation of chemotherapy and continuing until the completion of chemoradiotherapy.
In both groups, patients with potentially resectable disease undergo surgery no more than 12 weeks after completion of chemoradiotherapy.
Endoscopic tumor biopsy specimens are collected at baseline and on day 3 of radiotherapy. Samples are analyzed for cyclooxygenase (COX)-2 gene and protein expression; PGE2 secretion; apoptotic activity; caspase-3 activation; cytochrome c translocation; VEGF mRNA quantitation; and cellular proliferation. Laboratory techniques used include RT-PCR, IHC, enzyme immunoassay, TUNEL assay, colorimetric assay, and northern blotting.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 34 patients (8-10 in group 1 and 24 in group 2) will be accrued for this study.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
DISEASE CHARACTERISTICS:
Biopsy proven squamous cell carcinoma or adenocarcinoma of the esophagus
- Lesions including the gastroesophageal junction allowed provided the tumor involves less than 2 cm of gastric cardia
Meets 1 of the following criteria:
Clinical stage II, III, or IV disease AND planning to receive chemoradiotherapy either for preoperative or palliative indications (group 1)
- Suitable candidate for bimodality (palliative intent) or trimodality (curative intent) therapy
Clinical stage II or III disease AND candidate to receive chemoradiotherapy for preoperative indication followed by planned esophagectomy or esophagogastrectomy (group 2)
- Suitable candidate for trimodality (curative intent) therapy
- No tracheoesophageal fistula on bronchoscopy
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy > 3 months (group 1)
- Not pregnant
- Adequate nutrition
- WBC ≥ 4,000/μL
- ANC ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Serum creatinine ≤ 1.5 mg/dL
- Bilirubin ≤ 1.5 mg/dL
No other prior or concurrent malignancy other than curatively treated carcinoma in situ of the cervix; localized prostate cancer that was previously treated with local therapy more than 2 years ago with a PSA of less than 4 ng/mL; basal cell carcinoma of the skin; or superficial transitional cell carcinoma of the bladder
- Patients who have had a prior malignancy are eligible if they have been free of disease for ≥ 5 years
- No serious medical or psychiatric illnesses that would preclude giving informed consent or otherwise limit survival to less than 2 years
- No history of known NSAID-induced gastrointestinal bleeding
- No current peptic ulcer disease
- No active coronary artery disease
- No myocardial infarction or cerebrovascular accident within the past 3 months
- No history of refractory congestive heart failure or cardiomyopathy
PRIOR CONCURRENT THERAPY:
- More than 1 week since prior major surgery (group 1)
- More than 2 weeks since prior major surgery (group 2)
- No prior chemotherapy or radiotherapy
More than 30 days since prior cyclooxygenase-2 inhibitors (selective or non-selective), including, but not limited to, any of the following:
- Acetylsalicylic acid (aspirin)
- Piroxicam
- Diclofenac
- Meloxicam
- Indomethacin
- Fenoprofen
- Sulindac
- Flurbiprofen
- Tolmetin
- Ibuprofen
- Celecoxib
- Ketoprofen
- Rofecoxib
- Ketoprofen ER
- Valdecoxib
- Naproxen
- Meclofenamate
- Oxaprozin
- Mefenamic acid
- Etodolac
- Nabumetone
- Ketorolac
- No concurrent seizure medications
- No concurrent amifostine or other such agents
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Aktiv komparator: Cohort 1
Induction chemotherapy and chemoradiation without celecoxib
|
65mg/m2 given on days 1, 8 ,22 and 29 prior to surgery
Andre navne:
Cisplatin 30mg/m2 will be administered on days 1, 8, 22 and 29 prior to surgery
Andre navne:
4,500 cGy in 180 cGy fractions 5 days per week, over a period of 5 weeks
Surgery will occur prior to chemoradiation therapy for those patients with resectable disease
|
Eksperimentel: Cohort 2
Induction chemotherapy and chemoradiation with celecoxib
|
65mg/m2 given on days 1, 8 ,22 and 29 prior to surgery
Andre navne:
Cisplatin 30mg/m2 will be administered on days 1, 8, 22 and 29 prior to surgery
Andre navne:
4,500 cGy in 180 cGy fractions 5 days per week, over a period of 5 weeks
Surgery will occur prior to chemoradiation therapy for those patients with resectable disease
400 mg, orally, twice per day beginning on day minus 3 and continue until the end of chemoradiation with CPT-11 and Cisplatin
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Rates of cellular apoptosis and proliferation
Tidsramme: 5 weeks
|
Measure the rates of cellular apoptotis and proliferation in esophageal cancers from biopsy samples pre-study and during chemoradiation with and without celecoxib therapy
|
5 weeks
|
Rate of pathologic complete remission in patients with resectable disease
Tidsramme: 4 years
|
To determine if an acceptable rate of pathologic complete remissions can be achieved in a cohort of patients with potentially resectable esophageal carcinoma
|
4 years
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Number of subjects experiencing adverse events
Tidsramme: 30 days post radiation
|
Adverse events/toxicity will graded per the CTCAE criteria
|
30 days post radiation
|
Median overall survival of patients with resectable disease
Tidsramme: 4 years
|
Follow up for survival will occur at 3 month intervals during the first two years, then every 6 months during years 3 and 4.
|
4 years
|
Formation of prostaglandin E2 (PGE2) in tumor tissue
Tidsramme: 12 weeks
|
The ability of celecoxib to decrease formation of prostaglandin E2 (PGE2) in tumor tissue will be analyzed using a Wilcoxon signed rank test on the difference (log scale) of the pre- and post-treatment tumor concentrations of PGE2
|
12 weeks
|
Downstream effects of inhibition of cyclooxygenase 2 function
Tidsramme: 12 weeks
|
A difference in location of the mRNA expression of the two cohorts will be tested for using the Wilcoxon rank sum test.
A difference in the immunohistochemistry staining of the two cohorts will be tested for using polytomous logistic regression
|
12 weeks
|
Response Rate
Tidsramme: 4 years
|
Radiographic repsonse will be measured using RECIST critera in patients with unresectable esophageal cancer.
|
4 years
|
Samarbejdspartnere og efterforskere
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Bert H. O'Neil, MD, UNC Lineberger Comprehensive Cancer Center
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Sygdomme i fordøjelsessystemet
- Neoplasmer
- Neoplasmer efter sted
- Gastrointestinale neoplasmer
- Neoplasmer i fordøjelsessystemet
- Gastrointestinale sygdomme
- Neoplasmer i hoved og hals
- Esophageale sygdomme
- Esophageale neoplasmer
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Agenter fra det perifere nervesystem
- Enzymhæmmere
- Analgetika
- Sensoriske systemagenter
- Anti-inflammatoriske midler, ikke-steroide
- Analgetika, ikke-narkotisk
- Anti-inflammatoriske midler
- Antirheumatiske midler
- Cyclooxygenase-hæmmere
- Antineoplastiske midler
- Topoisomerasehæmmere
- Cyclooxygenase 2-hæmmere
- Topoisomerase I-hæmmere
- Celecoxib
- Irinotecan
Andre undersøgelses-id-numre
- LCCC 0203
- CDR0000561610 (Anden identifikator: NCI PDQ identifier)
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
produkt fremstillet i og eksporteret fra U.S.A.
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
Kliniske forsøg med Spiserørskræft
-
The Methodist Hospital Research InstituteAfsluttetEsophageal eller gastrisk perforering | Esophageal eller gastrisk lækageForenede Stater
-
Federal University of São PauloUkendtEsophageal forsnævring | Ætsende esophageal forsnævring | Peptisk esophageal forsnævring | Post-kirurgisk esophageal strikturBrasilien
-
Johns Hopkins UniversityTrukket tilbageEsophageal Perforation | Esophageal fistel | Forsnævring af spiserøret | Esophageal lækage | Endostitch | Esophageal stentForenede Stater
-
Mayo ClinicNational Cancer Institute (NCI)Aktiv, ikke rekrutterendeStadie III lungekræft AJCC v8 | Stadie II lungekræft AJCC v8 | Stadie IIA lungekræft AJCC v8 | Stadie IIB lungekræft AJCC v8 | Stadie IIIA Lungekræft AJCC v8 | Stadie IIIB Lungekræft AJCC v8 | Stadie I lungekræft AJCC v8 | Stadie IA1 Lungekræft AJCC v8 | Stadie IA2 Lungekræft AJCC v8 | Stadie IA3 lungekræft... og andre forholdForenede Stater
-
Mayo ClinicAfsluttetEsophageal Dilatation | Refraktær benign esophageal forsnævringForenede Stater
-
The Cleveland ClinicMedtronic - MITGAfsluttetEsophageal læsionForenede Stater
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)AfsluttetStadium IIIA Esophageal Adenocarcinom | Stadium IIIB Esophageal Adenocarcinom | Stadie IIIC Esophageal Adenocarcinom | Stadium IIB Esophageal Adenocarcinom | Stadium IB Esophageal Adenocarcinom | Stadie IIA Esophageal AdenocarcinomForenede Stater
-
University Medical Center GroningenAfsluttet
-
Mayo ClinicAfsluttetAchalasia | Esophageal Achalasia | Achalasia, esophagealForenede Stater
-
NYU Langone HealthTrukket tilbage
Kliniske forsøg med CPT- 11
-
Daiichi Sankyo Co., Ltd.AfsluttetMetastatisk tyktarmskræftJapan
-
University of California, San FranciscoAfsluttetGlioblastom | Gliosarkom | Anaplastisk astrocytom | Anaplastisk oligodendrogliomForenede Stater
-
Kazuhiko YoshimatsuHuman Genome Center, Institute of Medical Science, University of TokyoAfsluttetKolorektal cancerJapan
-
Icahn School of Medicine at Mount SinaiRekruttering
-
JenKem Technology Co., Ltd.Afsluttet
-
Assiut UniversityAktiv, ikke rekrutterende
-
National Cancer Institute (NCI)AfsluttetIldfast malignt fast neoplasma | Pineoblastom | Tilbagevendende malignt fast neoplasma | Tilbagevendende medulloblastom | Tilbagevendende neuroblastom | Tilbagevendende rhabdomyosarkom | Refraktær medulloblastom | Refraktær neuroblastom | Refraktær Rhabdomyosarkom | Embryonal tumor i centralnervesystemet med... og andre forholdForenede Stater, Canada
-
National Cancer Institute (NCI)Aktiv, ikke rekrutterendeVoksen fast neoplasmaForenede Stater
-
City of Hope Medical CenterNational Cancer Institute (NCI)Aktiv, ikke rekrutterendeTilbagevendende glioblastom | Tilbagevendende malignt gliom | Tilbagevendende WHO Grade III Gliom | Tilbagevendende gliosarkom | Tilbagevendende anaplastisk astrocytom | Tilbagevendende anaplastisk oligoastrocytom | Tilbagevendende Anaplastisk OligodendrogliomForenede Stater
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Trukket tilbageTilbagevendende Ewing-sarkom | Metastatisk Ewing-sarkomForenede Stater