Clinical trial 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
Official title: 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).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage III rectal cancer
stage IV rectal cancer
adenocarcinoma of the rectum
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2007-10-08
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Complete remission at ≥ 6 months by abdomino-pelvic-thoracic scan and a pelvic MRI
Secondary outcomes:
measure: Preoperative clinical response
measure: Progression-free survival
measure: Overall survival
measure: Early toxicity before surgery
measure: Early toxicity due to surgery (mortality at 30 days, postoperative complications, surgical recovery)
measure: Late toxicity
measure: Late radiotherapy toxicity by CTC AE v. 3.0
measure: Objective response of measurable metastases by RECIST
measure: Sexual function
measure: Downstaging and downsizing of patients with operable disease
measure: Surgical complications
measure: Sphincter function
measure: Predictive biomarkers of response to cetuximab
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonie
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer Georges-Francois Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Leon Berard
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Institut du Cancer de Montpellier - Val d'Aurelle
name: David Azria, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: