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Irinotecan, Cisplatin, and Radiation Therapy With or Without Celecoxib in Treating Patients With Stage II, Stage III, or Stage IV Esophageal Cancer

16. mai 2012 oppdatert av: UNC Lineberger Comprehensive Cancer Center

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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert 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.

Studietype

Intervensjonell

Registrering (Faktiske)

14

Fase

  • Fase 2

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Aktiv komparator: Cohort 1
Induction chemotherapy and chemoradiation without celecoxib
Legemiddel: CPT- 11
65mg/m2 given on days 1, 8 ,22 and 29 prior to surgery
Andre navn:
  • Irinotekan
Legemiddel: Cisplatin
Cisplatin 30mg/m2 will be administered on days 1, 8, 22 and 29 prior to surgery
Andre navn:
  • Cis-diammine-dichloro-platinum
Stråling: Radiation
4,500 cGy in 180 cGy fractions 5 days per week, over a period of 5 weeks
Fremgangsmåte: Surgery
Surgery will occur prior to chemoradiation therapy for those patients with resectable disease
Eksperimentell: Cohort 2
Induction chemotherapy and chemoradiation with celecoxib
Legemiddel: CPT- 11
65mg/m2 given on days 1, 8 ,22 and 29 prior to surgery
Andre navn:
  • Irinotekan
Legemiddel: Cisplatin
Cisplatin 30mg/m2 will be administered on days 1, 8, 22 and 29 prior to surgery
Andre navn:
  • Cis-diammine-dichloro-platinum
Stråling: Radiation
4,500 cGy in 180 cGy fractions 5 days per week, over a period of 5 weeks
Fremgangsmåte: Surgery
Surgery will occur prior to chemoradiation therapy for those patients with resectable disease
Legemiddel: Celecoxib
400 mg, orally, twice per day beginning on day minus 3 and continue until the end of chemoradiation with CPT-11 and Cisplatin

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
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
Tiltaksbeskrivelse
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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

UNC Lineberger Comprehensive Cancer Center

Samarbeidspartnere

National Cancer Institute (NCI)

Etterforskere

  • Hovedetterforsker: Bert H. O'Neil, MD, UNC Lineberger Comprehensive Cancer Center

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. mars 2005

Primær fullføring (Faktiske)

1. november 2006

Studiet fullført (Faktiske)

1. september 2010

Datoer for studieregistrering

Først innsendt

21. august 2007

Først innsendt som oppfylte QC-kriteriene

21. august 2007

Først lagt ut (Anslag)

23. august 2007

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

18. mai 2012

Siste oppdatering sendt inn som oppfylte QC-kriteriene

16. mai 2012

Sist bekreftet

1. mai 2012

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • LCCC 0203
  • CDR0000561610 (Annen identifikator: NCI PDQ identifier)

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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