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

Unicancer

Status and phase

Terminated

Phase 2

Conditions

Anal Cancer

Treatments

Other: laboratory biomarker analysis

Drug: fluorouracil

Radiation: radiation therapy

Drug: cisplatin

Biological: cetuximab

Study type

Interventional

Funder types

Other

Identifiers

NCT00955240

2007-007029-38 (EudraCT Number)

EU-20941 (Other Identifier)

CDR0000642638

FRE-FNCLCC-ACCORD-16-0708 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

16 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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