Clinical trial NCT00227747: Radiation Therapy and Capecitabine With or Without Oxaliplatin in Treating Patients Who Are Undergoing Surgery for Stage II or Stage III Rectal Cancer
Official title: Randomized Phase III Trial Comparing in a Preoperative Schedule the Result of Two Concurrent Chemoradiation Schemes (45 Gy + Capecitabine vs 50 Gy + Capecitabine - Oxaliplatin) on the Rate of Sterilization of the Operative Specimen in Resectable Rectal Carcinomas T3-4 No-2 Mo
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: adenocarcinoma of the rectum
stage II rectal cancer
stage III rectal cancer
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2005-09-28
Enrollment: 598
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving radiation therapy together with combination chemotherapy before surgery may shrink the tumor so it can be removed. It is not yet known whether giving radiation therapy together with capecitabine is more effective with or without oxaliplatin before surgery in treating rectal cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy, capecitabine, and oxaliplatin to see how well they work compared to radiation therapy and capecitabine in treating patients who are undergoing surgery for stage II or stage III rectal cancer.

Detailed description: OBJECTIVES:

Primary

* Compare the efficacy of neoadjuvant chemoradiotherapy comprising radiotherapy and capecitabine with vs without oxaliplatin followed by total mesorectal excision, in terms of the rate of complete surgical resection, in patients with resectable stage II or III rectal cancer.

Secondary

* Compare overall and disease-free survival of patients treated with these regimens.
* Compare clinical tumor response in patients treated with these regimens.
* Compare acute and late toxicity of these regimens in these patients.
* Determine biological parameters that predict tumor response and treatment-related toxicity in patients treated with these regimens.
* Compare sphincter preservation and function in patients treated with these regimens.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo radiotherapy once daily 5 days a week and receive capecitabine once daily 5 days a week in weeks 1-5.
* Arm II: Patient undergo radiotherapy and receive capecitabine as in arm I. Patients also receive oxaliplatin once weekly in weeks 1-5.

All patients undergo total mesorectal excision 6 weeks after completion of chemoradiotherapy.

PROJECTED ACCRUAL: A total of 590 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed adenocarcinoma of the rectum

  * T3-4, N0-2, M0 disease by endorectal ultrasound

    * T2 disease located in the low rectum allowed provided lower pole is ≤ 6 cm from the anal verge
* Tumor must be accessible to digital rectal examination (i.e., tumor located at low- or mid-rectum)
* Resectable disease treatable with chemoradiotherapy

  * No unresectable disease (i.e., T4 disease with high risk for incomplete gross resection \[i.e., R2\])

PATIENT CHARACTERISTICS:

Age

* 18 to 80

Performance status

* ECOG 0-2

Life expectancy

* Not specified

Hematopoietic

* WBC ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin \> 10 g/dL

Hepatic

* Alkaline phosphatase normal
* Bilirubin normal

Renal

* Creatinine ≤ 130 μmol/L
* No severe renal insufficiency

Cardiovascular

* No cardiac insufficiency
* No symptomatic coronary artery disease

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No contraindication to study treatment
* Prior acute intestinal obstruction allowed provided patient underwent surgical diversion with stoma
* No history of other cancer except basal cell skin cancer or carcinoma in situ of the cervix
* No peripheral neuropathy
* No uncontrolled diabetes
* No other uncontrolled severe disease
* No geographical, social, or psychological condition that would preclude study follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No prior chemotherapy for cancer
* No other concurrent chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* No prior radiotherapy for cancer

Surgery

* Not specified

Other

* No concurrent phenytoin
* No concurrent participation in another clinical trial of an experimental medical treatment

Primary outcomes:
measure: Rate of complete surgical resection
Secondary outcomes:
measure: Overall survival
measure: Disease-free survival
measure: Sphincter preservation
measure: Sphincter function
measure: Biological parameters that predict tumor response and treatment-related toxicity
measure: Acute and late toxicity
Other outcomes:
Locations:
city: Abbeville
country: France
facility: Centre Hospitalier d'Abbeville
city: Altkirch
country: France
facility: Centre Hospitalier
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Avignon
country: France
facility: Hopital Duffaut
city: Beziers
country: France
facility: Hopital de Beziers
city: Blois
country: France
facility: Centre Hospitalier de Blois
city: Bordeaux
country: France
facility: Hopital Saint Andre
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Bordeaux
country: France
facility: Clinique Tivoli
city: Boulogne Sur Mer
country: France
facility: Centre Hospitalier Docteur Duchenne
city: Bourgoin-Jallieu
country: France
facility: Centre Hospitalier Pierre Oudot
city: Caen
country: France
facility: CHU de Caen
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Chalon Sur Saone
country: France
facility: Clinique Sainte Marie
city: Chartres
country: France
facility: Hopital Louis Pasteur
city: Colmar
country: France
facility: Hopital Louis Pasteur
city: Creteil
country: France
facility: Centre Hospitalier Universitaire Henri Mondor
city: Dijon
country: France
facility: Hopital Drevon
city: Dijon
country: France
facility: Hopital Du Bocage
city: Gap
country: France
facility: Centre Hospitalier de Gap
city: Hyeres
country: France
facility: Clinique Sainte-Marguerite
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Departemental
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Libourne
country: France
facility: Hopital Robert Boulin
city: Lille
country: France
facility: Centre Oscar Lambret
city: Limoges
country: France
facility: Centre Hospital Regional Universitaire de Limoges
city: Limoges
country: France
facility: Hopital Jean Bernard
city: Longjumeau
country: France
facility: Centre Hospitalier General
city: Lormont
country: France
facility: Polyclinique des Quatre Pavillons
city: Lyon
country: France
facility: Centre Leon Berard
city: Macon
country: France
facility: Clinique J. B. Menis
city: Marseille
country: France
facility: Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
city: Marseille
country: France
facility: CHU de la Timone
city: Metz
country: France
facility: Hopital Notre-Dame de Bon Secours
city: Montbeliard
country: France
facility: Centre Hospitalier General Andre Boulloche
city: Montfermeil
country: France
facility: Centre Hospitalier Intercommunal Le Raincy - Montfermeil
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Montpellier
country: France
facility: Clinique Clementville
city: Mougins
country: France
facility: Clinique Plein Ciel
city: Mulhouse
country: France
facility: Centre Hospitalier de Mulhouse
city: Nantes-Saint Herblain
country: France
facility: Centre Regional Rene Gauducheau
city: Neuilly sur Seine
country: France
facility: Clinique Hartmann
city: Nevers
country: France
facility: Polyclinique du Val de Loire
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nimes
country: France
facility: C.H.U. de Nimes - Groupe Hospitals-Universitaire Caremeau
city: Orleans
country: France
facility: CHR D'Orleans - Hopital de la Source
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Paris
country: France
facility: Hopital Bichat - Claude Bernard
city: Paris
country: France
facility: Hopital Saint-Louis
city: Paris
country: France
facility: CHU Pitie-Salpetriere
city: Paris
country: France
facility: Hopital Tenon
city: Pau
country: France
facility: Centre Hospitalier - Pau
city: Perpignan
country: France
facility: Clinique Saint - Pierre
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Reims
country: France
facility: Institut Jean Godinot
city: Reims
country: France
facility: CHU - Robert Debre
city: Reims
country: France
facility: Polyclinique De Courlancy
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rodez
country: France
facility: Centre Hospitalier de Rodez
city: Saint Brieuc
country: France
facility: Clinique Armoricaine De Radiologie
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Saint Priest en Jarez
country: France
facility: Institut de Cancerologie de la Loire
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Toulouse
country: France
facility: Clinique Pasteur - Toulouse
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
city: Vannes
country: France
facility: Centre d'Oncologie Saint-Yves
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre Antoine Lacassagne
name: Jean-Pierre Gerard, MD
role: STUDY_CHAIR
References:
citation: Gerard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, Francois E, de La Roche G, Bouche O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahe MA, Becouarn Y, Dupuis O, Lledo G, Montoto-Grillot C, Conroy T. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol. 2010 Apr 1;28(10):1638-44. doi: 10.1200/JCO.2009.25.8376. Epub 2010 Mar 1.
citation: Azria D, Doyen J, Jarlier M, Martel-Lafay I, Hennequin C, Etienne P, Vendrely V, Francois E, de La Roche G, Bouche O, Mirabel X, Denis B, Mineur L, Berdah J, Mahe M, Becouarn Y, Dupuis O, Lledo G, Seitz J, Bedenne L, Gourgou-Bourgade S, Juzyna B, Conroy T, Gerard J. Late toxicities and clinical outcome at 5 years of the ACCORD 12/0405-PRODIGE 02 trial comparing two neoadjuvant chemoradiotherapy regimens for intermediate-risk rectal cancer. Ann Oncol. 2017 Oct 1;28(10):2436-2442. doi: 10.1093/annonc/mdx351.