Radiation Therapy, Cisplatin, Fluorouracil, and Cetuximab in Treating Patients With Locally Advanced Anal Cancer

Phase II Nonrandomized Multicenter Study of the Impact of Radiochemotherapy (65 Gy + Cisplatin + 5FU) Combined With Cetuximab in Patients Presenting With Locally Advanced Anal Cancer

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as fluorouracil and cisplatin, 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 may kill more tumor cells.

PURPOSE: This phase II trial is studying giving radiation therapy together with cisplatin, fluorouracil, and cetuximab to see how well it works in treating patients with locally advanced anal cancer.

Study Overview

• Status: Terminated
• Conditions: Anal Cancer
• Intervention / Treatment: Drug: fluorouracil; Radiation: radiation therapy; Other: laboratory biomarker analysis; Drug: cisplatin; Biological: cetuximab

Detailed Description

OBJECTIVES:

Primary

• Evaluate the objective response (complete and partial) 8 weeks after completion of study treatment comprising radiotherapy, chemotherapy (fluorouracil and cisplatin), and cetuximab followed by additional radiotherapy in patients with locally advanced anal cancer.

Secondary

• Evaluate colostomy-free survival.
• Evaluate the local control rate (objective response and stabilization) at 8 weeks.
• Evaluate relapse-free survival at 5 years.
• Evaluate the intermediate objective response at the end of week 5 of radiotherapy.
• Evaluate overall survival at 5 years.
• Evaluate the duration of response.
• Evaluate acute toxicities according to CTCAE v3.0.
• Evaluate late toxicities at 5 years according to CTCAE v3.0.
• Study the tumor markers associated with response (survival without relapse) and toxicity.
• Study the genotypes of Fc-receptor immunoglobulins (FCGR2A and FCGR3) and their association with skin toxicity, objective survival, and relapse-free survival.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV on days 0, 7, 14, 21, 28, and 35; fluorouracil IV on days 7-10 and 35-38; and cisplatin IV over 2 hours on days 7 and 35. Beginning on day 7, patients also undergo radiotherapy 5 days a week for 5 weeks (weeks 2-6). Two weeks after finishing this treatment, patients undergo additional radiotherapy* 5 days a week for 2 weeks (weeks 9 and 10).

NOTE: *Some patients may undergo brachytherapy.

Blood and tissue samples are collected for further analysis.

After completion of study treatment, patients are followed up for 4 years.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Institut Bergonié
  • Brest, France, 29609
    • CHU Hopital A. Morvan
  • Caen, France, 14076
    • Centre Regional Francois Baclesse
  • La Roche Sur Yon, France, F-85025
    • Centre Hospitalier departemental
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Limoges, France, 87042
    • Centre Hospital Regional Universitaire de Limoges
  • Lyon, France, 69373
    • Centre Leon Berard
  • Montpellier, France, 34298
    • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
  • Nantes-Saint Herblain, France, 44805
    • Centre Regional Rene Gauducheau
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Paris, France, 75970
    • Hopital Tenon
  • Paris, France, 75475
    • Hopital Saint-Louis
  • Paris, France, 75248
    • Institut Curie Hopital
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Rouen, France, 76031
    • Hopital Charles Nicolle
  • Saint-Gregoire, France, 35768
    • Centre Hospitalier Prive Saint-Gregoire
  • Toulouse, France, 31078
    • Clinique du parc
  • Toulouse, France, 31300
    • Groupe Oncorad Garonne
  • Vandoeuvre-les-Nancy, France, 54511
    • Centre Alexis Vautrin
  • Villejuif, France, F-94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed anal cancer

  • Squamous cell disease
  • Locally advanced, non-metastatic disease

  • One of the following clinical TNM stages:

    • T2, N0, M0 (largest diameter ≥ 3 cm)
    • T3-T4, N0, M0
    • Any T, N1-N3, M0
• No undifferentiated small cell carcinoma or adenocarcinoma
• Measurable disease according to RECIST criteria
• Undergone endorectal ultrasound or MRI to evaluate the primary tumor
• Undergone thoraco-abdomino-pelvic scan to evaluate tumor extension
• Disease suitable to receive radiotherapy and chemotherapy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Leukocytes ≥ 4,000/mm^3
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• Creatinine clearance > 60 mL/min
• ALT and AST ≤ 5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN
• Total bilirubin ≤ 1.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• No history of cancer within the past 8 years except for in situ cervical cancer or previously treated basal cell carcinoma of the skin
• No contraindications to any component of study therapy
• No serious uncontrolled illness
• No symptomatic grade 1 angina pectoris or angina pectoris ≥ grade 2
• No congestive heart failure
• No peripheral sensory neuropathy
• No uncontrolled diabetes
• No HIV positivity
• No geographical, social, or psychological situations that preclude medical follow up
• Affiliated with a social security system
• No patient deprived of liberty or under trusteeship

PRIOR CONCURRENT THERAPY:

• Patients with a diverting colostomy are eligible
• No prior excision of this tumor
• No prior chemotherapy or radiotherapy for the treatment of this cancer or any other history of radiotherapy or pelvic brachytherapy
• No concurrent coumarin anticoagulants, phenytoin, sorivudine or brivudine, antacids, or allopurinol
• Not registered in another clinical trial with an experimental drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Objective response (complete and partial) according to RECIST criteria at 8 weeks after completion of study treatment

Secondary Outcome Measures

Outcome Measure
Duration of objective response
Survival rate at 3 and 5 years
Colostomy-free survival at 3 and 5 years

Collaborators and Investigators

• Sponsor: UNICANCER
• Investigators: Principal Investigator: Eric Deutsch, MD, Gustave Roussy, Cancer Campus, Grand Paris

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): November 26, 2010
• Study Completion (Actual): November 26, 2010

Study Registration Dates

• First Submitted: August 7, 2009
• First Submitted That Met QC Criteria: August 7, 2009
• First Posted (Estimate): August 10, 2009

Study Record Updates

• Last Update Posted (Actual): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 7, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: stage II anal cancer; stage IIIA anal cancer; stage IIIB anal cancer; squamous cell carcinoma of the anus
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Anus Diseases; Anus Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Cisplatin; Fluorouracil; Cetuximab
• Other Study ID Numbers: CDR0000642638; FRE-FNCLCC-ACCORD-16-0708 (Other Identifier: LNCLCC); EU-20941 (Other Identifier: European union); 2007-007029-38 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No