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Preoperative Chemoradiation Followed by Chemotherapy for Locally Advanced Rectal Cancer (PREPARE)

12 september 2017 uppdaterad av: Sun Young Kim, National Cancer Center, Korea

A Randomized Phase II Trial of Preoperative Chemoradiation (Preop CRT) Followed by CapOx (Capecitabine Plus Oxaliplatin) Versus Preop CRT Alone for Locally Advanced Rectal Cancer (LARC)

The current standard treatment of locally advanced rectal cancer (clinical stage II or III) is preoperative radiation with chemotherapy (CRT) followed by surgery. But this approach can be suboptimal for patients with high risk features (more deeply-seated tumor or many regional lymph nodes involved)that are associated with recurrence. This study test a hypothesis that CRT followed by chemotherapy before surgery can improve efficacy of preoperative treatment.

Studieöversikt

Status

Okänd

Betingelser

Intervention / Behandling

Detaljerad beskrivning

Downstaging rate with CRT using fluoropyrimidine monotherapy is usually 30-40%.In MRI-defined high-risk patients, downstaging rate with conventional fluoropyrimidine-based monotherapy with radiation has not been shown. We assume that the downstaging rate of chemoradiation arm (control arm) would be 30%, and that addition of CapOx after CRT (experimental arm) may increase downstaging rate 30% to 50%. A sample size of 52 patients per group is needed have 85% power to detect downstaging rate = 50% as compared to 30% with type I error rate of 15%. We will perform one interim futility analysis when half of the patients are recruited and evaluated for the primary endpoint. O'Brien-Fleming boundary will be considered. Therefore, when 26 patients per arm are evaluated, the interim futility analysis will be performed, and when the Z score at the interim is less than -0.09192 (one-sided p-value greater than 0.5366192), the study will be stopped for futility. Considering 5% follow-up loss, a sample size of 55 per arm (a total of 110 patients) will be studied.

Studietyp

Interventionell

Inskrivning (Faktisk)

110

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Korea, Republiken av
      • Anyang, Korea, Republiken av
        • Hallym University Sacred Heart Hospital
      • Gangneung, Korea, Republiken av
        • Gangneung Asan Hospital
      • Seoul, Korea, Republiken av, 03722
        • Severance Hospital
      • Seoul, Korea, Republiken av, 05505
        • Asan Medical Center
      • Seoul, Korea, Republiken av, 06973
        • Chung-Ang University Hospital
    • Gyeonggi-do
      • Goyang, Gyeonggi-do, Korea, Republiken av, 410-769
        • National Cancer Center
      • Seongnam, Gyeonggi-do, Korea, Republiken av, 13620
        • Seoul National University Bundang Hospital

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

20 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  • histologically confirmed adenocarcinoma of the rectum
  • distal margin of tumor located from 0 to 12 cm from anal verge measured by digital rectal examination

  • high risk clinical stage II or III in MRI (satisfying at least one of the followings)

    • circumferential resection margin < 1 mm involved
    • low-lying tumor below anal verge 3 cm
    • T3 > 5 mm extramural spread
    • T4 (involving surrounding structures or peritoneum)
    • cN2 (4 or more mixed signal intensity or irregularly bordered node or tumor deposit)
  • age 20 years or more
  • ECOG (Eastern Cooperative Oncology Group) performance status 0-2
  • No prior chemotherapy, radiotherapy to pelvis
  • Adequate bone marrow function
  • Adequate renal function
  • Adequate hepatic function
  • patients must sign the informed consent indicating that they were aware of the investigational nature of the study in keeping with the policy of the hospital

Exclusion Criteria:

  • malignant disease of the rectum other than adenocarcinoma or arisen from chronic inflammatory bowel disease
  • any unresected synchronous colon cancer
  • any distant metastases
  • intestinal obstruction or impending obstruction, but decompressing colostomy is permitted
  • any previous or concurrent malignancy withih 5 years other than non-melanoma skin cancer / in situ cancer of uterine cervix / early gastric cancer / thyroid cancer of low risk
  • any other morbidity or situation with relative contraindication for chemoradiotherapy
  • patients with history of significant gastric or small bowel resection, or malabsorption syndrome, or other lack of integrity of the upper gastrointestinal tract that may compromise the absorption of capecitabine
  • pregnant or lactating women or patients of childbearing potential not predicting adequate contraception

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: chemoradiation followed by CapOx
preoperative chemoradiation 50.4Gy with capecitabine or 5-fluorouracil/leucovorin (pelvic radiation capecitabine 5-fluorouracil) followed by 2 cycles of chemotherapy (Capecitabine Oxaliplatin - CapOx) and surgery (total mesorectal excision)
Läkemedel: Capecitabine Oxaliplatin
after completion of chemoradiation, two cycles of capecitabine (850mg/m2 twice daily from D1 evening to D15 morning) and oxaliplatin (100mg/m2 on D1) will be administered every 3 weeks.
Andra namn:
  • Xeloda
  • Oxalitin
Strålning: pelvic radiation capecitabine 5-fluorouracil
50.4Gy of pelvic radiation with capecitabine or 5-fluorouracil
Andra namn:
  • xeloda
  • preoperative chemoradiation
Aktiv komparator: chemoradiation
preoperative chemoradiation 50.4Gy with capecitabine or 5-fluorouracil/leucovorin (pelvic radiation capecitabine 5-fluorouracil) followed by rest for 8 weeks and surgery (total mesorectal excision)
Strålning: pelvic radiation capecitabine 5-fluorouracil
50.4Gy of pelvic radiation with capecitabine or 5-fluorouracil
Andra namn:
  • xeloda
  • preoperative chemoradiation

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
downstaging rate
Tidsram: expected average of 15 weeks after start of study treatment
downstaging rate is defined as the proportion of patients with ypStage (pathologic stage after preoperative treatment) 0 or I (from pathologic findings after preoperative treatment and surgery) out of all patients who were assigned to each arm.
expected average of 15 weeks after start of study treatment

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
pathologic response
Tidsram: expected average of 15 weeks after start of study treatment
pathologic response is assessed by Dworak's grading system from postoperative specimen.
expected average of 15 weeks after start of study treatment
radiologic response rate
Tidsram: expected average of 14 weeks after start of study treatment
radiologic response will be assessed according to RECIST (Response Evaluation Criteria in Solid Tumors) guideline 1.1
expected average of 14 weeks after start of study treatment
toxicity profile
Tidsram: expected average of 35 weeks after start of study treatment
Toxicities or any adverse events during study treatment, surgery and follow-up period will be assessed according to NCI CTCAE (Common Terminology Criteria for Adverse Events) version 4.0
expected average of 35 weeks after start of study treatment
pattern of failure
Tidsram: 3 years after surgery
if any recurrent lesion is noticed, anatomic sites of recurrent lesions and the date and the name of exam or imaging study (physical exam, CT or MRI…) will be recorded in case report form.
3 years after surgery
local control rate
Tidsram: 3 years after surgery
Local recurrence is defined as tumor recurrence confined in radiation field (pelvic cavity). Cumulative incidence of local recurrence will be suggested.
3 years after surgery
relapse-free survival
Tidsram: 3 years after surgery
Time from date of operation to date of recurrence of disease or deaths due to recurrence or progression of disease.
3 years after surgery
Disease-free survival
Tidsram: 3 years after surgery
time from date of operation to date of recurrence of disease, a new occurrence of secondary colorectal cancer, a new occurrence of other malignancy, or deaths from any cause.
3 years after surgery
overall survival
Tidsram: 3 years after surgery
time from date of operation to date of death due to any cause.
3 years after surgery
quality of life
Tidsram: before study treatment, 7 weeks after completion of chemoradiation, and at 4 weeks after surgery
quality of life will be measured with FACT-C
before study treatment, 7 weeks after completion of chemoradiation, and at 4 weeks after surgery

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

National Cancer Center, Korea

Samarbetspartners

Korean Cancer Study Group

Utredare

  • Studiestol: Sun Young Kim, MD, Asan Medical Center

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 juni 2014

Primärt slutförande (Faktisk)

1 september 2017

Avslutad studie (Förväntat)

1 december 2019

Studieregistreringsdatum

Först inskickad

11 september 2013

Först inskickad som uppfyllde QC-kriterierna

25 september 2013

Första postat (Uppskatta)

30 september 2013

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

13 september 2017

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

12 september 2017

Senast verifierad

1 september 2017

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • KCSG CO14-03

Plan för individuella deltagardata (IPD)

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