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Neoadjuvant Accelerated Short Course Radiation Therapy With Photons and Capecitabine for Resectable Pancreatic Cancer

12. april 2018 oppdatert av: Harvey Mamon, MD, PhD, Dana-Farber Cancer Institute

Phase I/II Study of Neoadjuvant Accelerated Short Course Radiation Therapy With Photons and Capecitabine for Resectable Pancreatic Cancer

The purpose of this research study is to determine if it is possible to deliver high dose radiation in one week while also giving the drug capecitabine for the treatment of pancreatic cancer prior to surgery, to determine if this treatment can be given safely for the treatment of pancreatic cancer prior to surgery and, to determine if this treatment can improve the local control pancreatic cancer prior to surgery compared to historical controls of standard treatment.

Studieoversikt

Status

Avsluttet

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

OBJECTIVES:

Primary

  • Phase I: To determine the feasibility and tolerability of radiation therapy for pancreatic cancer delivered with high dose external beam radiation in a one week accelerated schedule with concurrent capecitabine
  • Phase II: To demonstrate a grade 3 or greater (any) toxicity rate of less than 20%

Secondary

  • To determine local control and recurrence patterns of pancreatic cancer relative to a standard regimen of 50.4 Gy as seen in historical controls
  • To determine the pathologic response rate
  • To determine the progression-free survival
  • To determine the surgical morbidity
  • To determine 30-day post-operative mortality after pancreatic resection

Studietype

Intervensjonell

Registrering (Faktiske)

10

Fase

  • Fase 2
  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • Massachusetts
      • Boston, Massachusetts, Forente stater, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, Forente stater, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, Forente stater, 02214
        • Massachusetts General Hospital

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

Inclusion Criteria:

  • Cytologic or histologic proof of pancreatic ductal carcinoma is required prior to treatment.
  • No evidence of metastatic disease as determined by chest CT scan, abdominal CT scan (or MRI with gadolinium and/or manganese), and all patients must be staged with a physical exam, chest CT, and abdominal CT with intravenous contrast.
  • Only potentially resectable patients are eligible. Potentially resectable is defined as: a)no extrapancreatic disease, b)no evidence (on CT) of involvement of the celiac axis or superior mesenteric artery, and c)no evidence (on CT or MRI) of occlusion of the superior mesenteric vein or superior mesenteric-portal venous confluence.
  • 18 years of age or older
  • ECOG Performance status of 0 or 1
  • Women of child bearing potential must practice adequate contraception and to refrain from breast feeding. Female patients must have a negative pregnancy test within 7 days of treatment
  • Lab values as specified in the protocol

Exclusion Criteria:

  • Patients cannot have hepatic or peritoneal metastases detected by imaging or laparoscopy prior to chemoradiation
  • Serious concomitant systemic disorders incompatible with the study, such as significant cardiac or pulmonary morbidity, or ongoing infection as manifested by fever
  • Pregnant or lactating women
  • Life expectancy < 3 months
  • Serious, uncontrolled, concurrent infection(s)
  • Any prior chemotherapy or radiation for treatment of the patient's pancreatic tumor
  • Treatment for other cancers within the last five years, except cured non-melanoma skin cancer and treated in situ cervical cancer
  • Clinically significant cardiac disease or myocardial infarction within the last 12 months
  • Other serious uncontrolled medical conditions that the investigator feels might compromise study participation
  • Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
  • Known, existing uncontrolled coagulopathy
  • Unwillingness to participate or inability to comply with the protocol for the duration of the study
  • Any prior fluoropyrimidine therapy (unless given in an adjuvant setting and completed at least 6 months earlier)
  • Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil or known DPD deficiency
  • Participation in any investigational drug study within 4 weeks preceding the start of study treatment
  • History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intake
  • Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery
  • Patients should not be on cimetidine as it can decrease the clearance of 5-FU. Another H2-blocker or proton pump inhibitor may be substituted before study entry

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: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Phase 1 Cohort 1: Photon Rad (30 Gy/12 days)+Capecitabine

Neoadjuvant Short-Course Photon Radiation:

At dose level 1, a total dose of 30 Gy in 10 fractions (3 Gy/day) was prescribed to the 95% isodose and administered 5 days per week over 12 days.

Chemotherapy:

Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.

Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
Legemiddel: Capecitabin
Andre navn:
  • Xeloda
Stråling: Neoadjuvant Short-Course Photon Radiation
Eksperimentell: Phase I Cohort 2: Photon Rad (25 Gy/11 days)+Capecitabine

Neoadjuvant Short-Course Photon Radiation:

At dose level 2, a total dose of 25 Gy in 5 fractions was prescribed to the 95% isodose and administered at 5 Gy per fraction over 11 days.

Chemotherapy:

Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.

Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
Legemiddel: Capecitabin
Andre navn:
  • Xeloda
Stråling: Neoadjuvant Short-Course Photon Radiation
Eksperimentell: Phase I Cohort 3: Photon Rad (25 Gy/5 days)+Capecitabine

Neoadjuvant Short-Course Photon Radiation:

At dose level 3, a total dose of 25 Gy in 5 fractions was prescribed to the 95% isodose and administered at 5 Gy per fraction over 5 days.

Chemotherapy:

Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.

Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
Legemiddel: Capecitabin
Andre navn:
  • Xeloda
Stråling: Neoadjuvant Short-Course Photon Radiation
Eksperimentell: All Phase I: Photon Rad+Capecitabine

Neoadjuvant Short-Course Photon Radiation:

All Phase I participants received the radiation regimen according to the established dose escalation schedule.

Chemotherapy:

Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.

Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
Legemiddel: Capecitabin
Andre navn:
  • Xeloda
Stråling: Neoadjuvant Short-Course Photon Radiation
Eksperimentell: Phase II: Photon Rad (MTD)+Capecitabine

Neoadjuvant Short-Course Photon Radiation:

Phase II participants received the radiation regimen established in the Phase I study (MTD).

Chemotherapy:

Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.

Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.
Legemiddel: Capecitabin
Andre navn:
  • Xeloda
Stråling: Neoadjuvant Short-Course Photon Radiation

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Neoadjuvant Short-Course Photon Radiation Therapy Maximum Tolerated Dose (MTD) [Phase I]
Tidsramme: within 3 weeks of the start of chemoradiation therapy
Neoadjuvant short-course photon radiation therapy MTD in combination with capecitabine 825 mg/m2 orally BID for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If none of 3 initial patients or only 1 of 6 patients have a DLT on dose level 3 then 6 additional patients are treated at this dose. If during this expansion, the rate of DLT exceeds 30% then the next lower dose level is declared the MTD. If no DLTs are observed, the MTD is not reached.
within 3 weeks of the start of chemoradiation therapy
Dose Limiting Toxicity (DLT) [Phase I]
Tidsramme: within 3 weeks of the start of chemoradiation therapy
DLT occurring within 3 weeks of the start of chemoradiation therapy was defined as: Grade 3 non-hematologic or hematologic toxicity requiring interruption of >7 days (d) of chemo or >3d chemoradiation; Grade 4 non-hematologic; Grade 4 neutropenia or thrombocytopenia; Treatment-related death; Delays in surgery >3 weeks due to treatment-related toxicity. A 30% increase in any surgical complication rate beyond those previously established rates (readmission rate: 16%; pancreatic fistula/intra-abdominal abscess/infection rate: 27%, major intra-abdominal bleeding requiring return to OR: 1.6%, delayed gastric emptying: 4.4%, and superficial wound infection rate: 8%) was also considered a DLT.
within 3 weeks of the start of chemoradiation therapy
Grade 3-5 Toxicity Rate [Phase II]
Tidsramme: within 3 weeks of the start of chemoradiation therapy
All Grade 3-5 events based on CTCAEv3 related to the accelerated dose (attribution possible, probable, definite) as reported on case report forms.
within 3 weeks of the start of chemoradiation therapy

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Local Recurrence Rate [Phase II]
Tidsramme: Disease was assessed radiologically at baseline and after treatment every 6 months for first 2 years and annually in years 3-5.
Local recurrence rate is defined as the proportion of patients with evidence of tumor recurrence within the radiation field based on RECIST criteria. Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Disease was assessed radiologically at baseline and after treatment every 6 months for first 2 years and annually in years 3-5.
Pathologic Response Rate [Phase II]
Tidsramme: Assessed after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy
Pathologic response rate is the proportion of patients with the pathologic specimen absent any viable tumor cell. Pathological review of the pancreaticoduodenectomy specimen will be performed according to the AJCC Staging Classification, 6th edition. Initial gross evaluation and identification of resection margins will be performed jointly by the surgeon and the pathologist.
Assessed after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy
Progression-Free Survival (PFS) [Phase II]
Tidsramme: Disease was assessed radiologically at baseline and after treatment every 6 months for first 2 years and annually in years 3-5.
Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Patients alive whose disease had not progressed are censored at date of last disease evaluation
Disease was assessed radiologically at baseline and after treatment every 6 months for first 2 years and annually in years 3-5.
Surgical Morbidity Rate [Phase II]
Tidsramme: Assessed after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy
The proportion of patients experienced any grade 3-4 adverse event based on CTCAEv3 related to the surgery (attribution possible, probable, definite) as reported on case report forms.
Assessed after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy
Surgical Mortality Rate [Phase II]
Tidsramme: Assessed up to 30 days after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy
The proportion of patients with a death related to the surgery (CTCAEv3 attribution possible, probable, definite).
Assessed up to 30 days after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy

Samarbeidspartnere og etterforskere

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

Sponsor

Dana-Farber Cancer Institute

Samarbeidspartnere

Massachusetts General Hospital
Brigham and Women's Hospital

Etterforskere

  • Hovedetterforsker: Harvey Mamon, MD, PhD, Brigham and Women's Hospital/Dana-Farber Cancer Institute

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

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 (Faktiske)

1. desember 2009

Primær fullføring (Faktiske)

30. desember 2011

Studiet fullført (Faktiske)

30. desember 2011

Datoer for studieregistrering

Først innsendt

27. april 2009

Først innsendt som oppfylte QC-kriteriene

27. april 2009

Først lagt ut (Anslag)

28. april 2009

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

11. mai 2018

Siste oppdatering sendt inn som oppfylte QC-kriteriene

12. april 2018

Sist bekreftet

1. april 2018

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 08-375

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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