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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

Primary Purpose

Colorectal Cancer

Status

Terminated

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

cetuximab

capecitabine

fluorouracil

leucovorin calcium

oxaliplatin

adjuvant therapy

conventional surgery

neoadjuvant therapy

radiation therapy

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage III rectal cancer, stage IV rectal cancer, adenocarcinoma of the rectum

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Institut Bergonie
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Centre Oscar Lambret
Centre Leon Berard
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
Centre Antoine Lacassagne
Centre Hospitalier Lyon Sud
Centre Rene Huguenin
Centre Alexis Vautrin
Institut Gustave Roussy

Outcomes

Primary Outcome Measures

Complete remission at ≥ 6 months by abdomino-pelvic-thoracic scan and a pelvic MRI

Secondary Outcome Measures

Preoperative clinical response

Progression-free survival

Overall survival

Early toxicity before surgery

Early toxicity due to surgery (mortality at 30 days, postoperative complications, surgical recovery)

Late toxicity

Late radiotherapy toxicity by CTC AE v. 3.0

Objective response of measurable metastases by RECIST

Sexual function

Downstaging and downsizing of patients with operable disease

Surgical complications

Sphincter function

Predictive biomarkers of response to cetuximab

Full Information

NCT ID

NCT00541112

First Posted

October 5, 2007

Last Updated

February 7, 2020

Sponsor

UNICANCER

1. Study Identification

Unique Protocol Identification Number

NCT00541112

Brief Title

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

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Terminated

Why Stopped

Toxicity and lack of efficacy

Study Start Date

October 29, 2007 (Actual)

Primary Completion Date

January 29, 2010 (Actual)

Study Completion Date

January 29, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

UNICANCER

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer

Keywords

stage III rectal cancer, stage IV rectal cancer, adenocarcinoma of the rectum

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

19 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

cetuximab

Intervention Type

Drug

Intervention Name(s)

capecitabine

Intervention Type

Drug

Intervention Name(s)

fluorouracil

Intervention Type

Drug

Intervention Name(s)

leucovorin calcium

Intervention Type

Drug

Intervention Name(s)

oxaliplatin

Intervention Type

Procedure

Intervention Name(s)

adjuvant therapy

Intervention Type

Procedure

Intervention Name(s)

conventional surgery

Intervention Type

Procedure

Intervention Name(s)

neoadjuvant therapy

Intervention Type

Radiation

Intervention Name(s)

radiation therapy

Primary Outcome Measure Information:

Title

Complete remission at ≥ 6 months by abdomino-pelvic-thoracic scan and a pelvic MRI

Secondary Outcome Measure Information:

Title

Preoperative clinical response

Title

Progression-free survival

Title

Overall survival

Title

Early toxicity before surgery

Title

Early toxicity due to surgery (mortality at 30 days, postoperative complications, surgical recovery)

Title

Late toxicity

Title

Late radiotherapy toxicity by CTC AE v. 3.0

Title

Objective response of measurable metastases by RECIST

Title

Sexual function

Title

Downstaging and downsizing of patients with operable disease

Title

Surgical complications

Title

Sphincter function

Title

Predictive biomarkers of response to cetuximab

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Azria, MD, PhD

Organizational Affiliation

Institut du Cancer de Montpellier - Val d'Aurelle

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institut Bergonie

City

Bordeaux

ZIP/Postal Code

33076

Country

France

Facility Name

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

City

Dijon

ZIP/Postal Code

21079

Country

France

Facility Name

Centre Oscar Lambret

City

Lille

ZIP/Postal Code

59020

Country

France

Facility Name

Centre Leon Berard

City

Lyon

ZIP/Postal Code

69373

Country

France

Facility Name

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

City

Montpellier

ZIP/Postal Code

34298

Country

France

Facility Name

Centre Antoine Lacassagne

City

Nice

ZIP/Postal Code

06189

Country

France

Facility Name

Centre Hospitalier Lyon Sud

City

Pierre Benite

ZIP/Postal Code

69495

Country

France

Facility Name

Centre Rene Huguenin

City

Saint Cloud

ZIP/Postal Code

92210

Country

France

Facility Name

Centre Alexis Vautrin

City

Vandoeuvre-les-Nancy

ZIP/Postal Code

54511

Country

France

Facility Name

Institut Gustave Roussy

City

Villejuif

ZIP/Postal Code

F-94805

Country

France

12. IPD Sharing Statement

Learn more about this trial

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

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