Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Capecitabine

Mitomycins

Mitomycin

Panitumumab

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

Antineoplastic Agents, Immunological

RADIOTHERAPY: daily fraction dose of 1.8Gy , 5 days a week between day 1 and 45 Intensity modulated radiotherapy (IMRT), using a linac based facility or helical tomotherapy, is obligatory.

The first treatment sequence consists of a total dose of 36 Gy in 20 daily fractions of 1.8 Gy on five days a week.

The second treatment sequence consists of a total dose of 23.4 Gy in 13 daily fractions of 1.8 Gy on five days a week.

PANITUMUMAB: 6 mg/kg IV over 60 min infusion on days 1, 15 and 29

MITOMYCIN: 10 mg/m2 IV over 15 min infusion on days 1 and 29

CAPECITABINE: 825 mg/m2 oral twice daily on days 1 to 45

External beam radiotherapy (daily fraction dose 1.8Gy) on Monday through Friday starting on study day 1.

* Days 1-28, dose of 36 Gy in 1.8 Gy/fraction (20 fractions) to the clinical target volume 1 (CTV1) including the primary tumor and involved lymph nodes and areas at risk for metastatic spread (which includes gross tumour volumes (GTV) and a 1-cm expansion, mesorectal space, inguinal, femoral, external iliac, internal iliac, and common iliac vessels).
* Days 29-45, a boost dose of 23.4 Gy in 1.8 Gy/fraction (13 fractions) to the GTV.

RADIOTHERAPY

6 mg/kg IV administered over 60 min infusion on days 1,15 and 29.

PANITUMUMAB

10 mg/m2 IV administered over 15 min infusion on days 1 and 29.

MITOMYCIN

825mg/m2 orally twice daily on study days 1 through 45.

CAPECITABINE

Oscar Matzinger, MD

There is increasing evidence of a role of EGFR, treatment with EGFR-inhibitors in anal cancer and synergies of EGFR-inhibitors with radiotherapy. Addition of the human anti-EGFR antibody Panitumumab to chemoradiotherapy seems therefore solidly justified. This trial investigates concurrent panitumumab/capecitabine/mitomycin concurrent to IMRT-radiotherapy. Treatment components used in this study have been selected on scientific rationale. The trial regimen should be feasible with acceptable toxicity and outcome similar to historic series.

OBJECTIVES:

Primary:

-To assess efficacy of treatment regimen composed of capecitabine, mitomycin, panitumumab, and radiotherapy in terms of locoregional control rate in patients with stage II-IIIB squamous-cell carcinoma of the anal canal.

Secondary:

* To further assess efficacy of this regimen based on complete response (CR) rate, colostomy-free survival, functional colostomy-free survival, overall survival (OS), and progression-free survival (PFS).
* To assess the tolerability and safety profile of this regimen.
* To assess the role of PET for staging and outcome prediction (for those patients who had PET following local standards).

Phase II Study of Concomitant Intensity-modulated Radiotherapy Combined to Capecitabine, Mitomycin and Panitumumab in Patients With Stage II-IIIB Squamous-cell Carcinoma of the Anal Canal

Tumor assessment will be done by the investigator according to the RECIST 1.1. criteria.

2-year colostomy-free survival (patients without colostomy two-years after treatment start).

2-year functional colostomy-free survival (patients without colostomy and without stool incontinence or other sphincter symptoms interfering with activities of daily life two years after treatment start, which correspond to grade 3 toxicity according to common toxicity criteria National Cancer Institute-Common Toxicity Criteria for Adverse Event (NCI-CTCAE) version 4.0.

2-year overall survival (proportion of patients alive two years after treatment start) and median overall survival (median of the interval (days) between treatment start and death for any cause).

2-year PFS (proportion of patients progression-free two years after treatment start) and median PFS according to the RECIST 1.1 criteria. PFS is defined as the interval (days) between registration and the date of progression (based on the actual tumor assessment date), or death for any cause, whichever comes first. The death of a patient without a reported progression will be considered as an event on the date of death. Patients who have neither progressed nor died will be censored on the date of last evaluable tumor assessment. Patients who had no post-baseline assessments and did not have an event will be censored at the time of registration.

Toxicities will be assessed according to the NCI-CTCAE (version 4.0).

Predictive value of PET for PFS. Comparison of PET for determination of complete response with radiologic response and clinical response.

Spots Global Cancer Trial Database for carcinoma of anal canal