- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00541112
Radiation Therapy, Chemotherapy, and Cetuximab Followed by Surgery, Chemotherapy, and Cetuximab in Treating Patients With Locally Advanced or Metastatic Rectal Cancer That Can Be Removed by Surgery
Phase II Multicenter Study of the Impact of the Therapeutic Sequence of Radiochemotherapy (50 Gy + Capecitabine + Oxaliplatin + Cetuximab) Followed by Total Mesorectal Excision Surgery Then Post-surgery Chemotherapy (FOLFOX 4 + Cetuximab) in Synchronous Locally Advanced or Metastatic Cancers of the Rectum With Metastases Resectable From the Start (T3-4 Nx or T2 N+ M1).
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as capecitabine, oxaliplatin, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving radiation therapy together with combination chemotherapy and cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy and cetuximab after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase II clinical trial is studying how well giving radiation therapy together with chemotherapy and cetuximab followed by surgery, chemotherapy, and cetuximab works in treating patients with locally advanced or metastatic rectal cancer that can be removed by surgery.
Studieoversikt
Status
Forhold
Detaljert beskrivelse
OBJECTIVES:
Primary
- Determine the complete remission rate at 6 months after neoadjuvant radiotherapy, capecitabine, and oxaliplatin (XELOX), and cetuximab followed by surgery, adjuvant FOLFOX 4, and cetuximab in patients with synchronous locally advanced or metastatic cancer of the rectum with resectable metastases (T3-4 Nx or T2 N+ M1).
Secondary
- Determine progression-free survival.
- Determine overall survival.
- Assess toxicities.
- Evaluate objective response in patients with measurable metastases.
- Determine the rate of local recurrence.
- Evaluate the downstaging and downsizing of patients with operable disease.
- Evaluate surgical complications in patients with operable disease.
- Evaluate biological markers predictive of response to cetuximab.
OUTLINE: This is a multicenter study.
- Neoadjuvant therapy: Patients undergo radiotherapy for 5 weeks and receive concurrent oral capecitabine twice daily on days 1-5 of each week and oxaliplatin IV over 2 hours on day 1 of each week (XELOX). Patients also receive cetuximab IV on day 1 of the first week and on days 1-7 of weeks 2-5.
- Surgery: At 6 weeks after completing chemoradiotherapy, patients with resectable disease undergo surgery comprising total mesorectal excision. Patients with progressive disease, nonresectable tumor, or who require R2 surgery are removed from the study.
- Adjuvant therapy: Patients who undergo surgery, with or without removal of metastases, receive FOLFOX 4, comprising oxaliplatin IV over 2 hours, fluorouracil IV over 46 hours, and leucovorin calcium IV on day 1, and cetuximab IV. Treatment repeats every 2 weeks for up to 6 courses (approximately 3 months). Patients who have not undergone prior surgical resection of metastases may have surgery to remove metastases after completing this second regimen of chemotherapy.
After completion of study therapy, patients are followed periodically for up to 5 years.
Studietype
Registrering (Faktiske)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
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-
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Bordeaux, Frankrike, 33076
- Institut Bergonie
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Dijon, Frankrike, 21079
- Centre de Lutte Contre le Cancer Georges-Francois Leclerc
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Lille, Frankrike, 59020
- Centre Oscar Lambret
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Lyon, Frankrike, 69373
- Centre Leon Berard
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Montpellier, Frankrike, 34298
- Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
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Nice, Frankrike, 06189
- Centre Antoine Lacassagne
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Pierre Benite, Frankrike, 69495
- Centre Hospitalier Lyon Sud
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Saint Cloud, Frankrike, 92210
- Centre René Huguenin
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Vandoeuvre-les-Nancy, Frankrike, 54511
- Centre Alexis Vautrin
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Villejuif, Frankrike, F-94805
- Institut Gustave Roussy
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-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
DISEASE CHARACTERISTICS:
Histologically confirmed adenocarcinoma of the rectum
Locally advanced (T3-4 Nx) or metastatic (T2 N+ M1) synchronous disease
- Metastases must be resectable
- Primary tumor examined by endorectal echography and MRI
- Measurable disease by thoraco-abdomino-pelvic scanner
- Disease considered susceptible to treatment with radiotherapy and chemotherapy
- No diffuse metastases considered nonresectable
- No acute occlusion not caused by colostomy
PATIENT CHARACTERISTICS:
Inclusion criteria:
- ECOG performance status 0-2
- WBC ≥ 4,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 10 g/dL
- Creatinine ≤ 130 µmol/L
- Transaminases ≤ 5 times upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients of must use effective contraception
Exclusion criteria:
- Contraindication to therapy with capecitabine, oxaliplatin, cetuximab, and/or radiotherapy
- Impossible to perform translational analyses
- Uncontrolled severe illness
- Severe renal or hepatic insufficiency
- Cardiac insufficiency or symptomatic coronary disease
- Sensitive peripheral neuropathy
- Uncontrolled diabetes
- Other malignancy within the past 10 years except previously treated basal cell skin cancer or carcinoma in situ of the cervix
- Impossible to participate in study due to geographic, social, or psychiatric reasons
- Patients who are under supervision or incarcerated
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior anticancer chemotherapy or radiotherapy for this cancer
- No therapy with coumarin anticoagulants, phenytoin, sorivudine, brivudine, antacids, or allopurinol
- No concurrent participation in another therapeutic study or receiving another experimental drug
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Hva måler studien?
Primære resultatmål
Resultatmål |
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Complete remission at ≥ 6 months by abdomino-pelvic-thoracic scan and a pelvic MRI
|
Sekundære resultatmål
Resultatmål |
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Progresjonsfri overlevelse
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Total overlevelse
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Seksuell funksjon
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Sen toksisitet
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Kirurgiske komplikasjoner
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Sphincter funksjon
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Preoperative clinical response
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Early toxicity before surgery
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Early toxicity due to surgery (mortality at 30 days, postoperative complications, surgical recovery)
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Late radiotherapy toxicity by CTC AE v. 3.0
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Objective response of measurable metastases by RECIST
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Downstaging and downsizing of patients with operable disease
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Predictive biomarkers of response to cetuximab
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Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: David Azria, MD, PhD, Institut du Cancer de Montpellier - Val d'aurelle
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
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 (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Sykdommer i fordøyelsessystemet
- Neoplasmer
- Neoplasmer etter nettsted
- Gastrointestinale neoplasmer
- Neoplasmer i fordøyelsessystemet
- Gastrointestinale sykdommer
- Kolonsykdommer
- Tarmsykdommer
- Intestinale neoplasmer
- Rektale sykdommer
- Kolorektale neoplasmer
- Rektale neoplasmer
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Antimetabolitter, antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Beskyttende agenter
- Antineoplastiske midler, immunologiske
- Mikronæringsstoffer
- Vitaminer
- Kalsiumregulerende hormoner og midler
- Motgift
- Vitamin B kompleks
- Fluorouracil
- Capecitabin
- Oksaliplatin
- Leucovorin
- Kalsium
- Levoleucovorin
- Cetuximab
Andre studie-ID-numre
- CDR0000565937
- FRE-FNCLCC-ACCORD-14/0604 (Annen identifikator: FNCLCC)
- EU-20759
- 2006-003336-30 (EudraCT-nummer)
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
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