Phase III Study Evaluating Induction Chemotherapy Followed by Chemoradiotherapy Compared to Standard Chemoradiotherapy for Locally Advanced SCCA

Summary

Squamous cell carcinoma of the anus is still a rare disease but its incidence increases mostly due to its association with human papillomavirus (HPV). When localized, the standard treatment combines radiotherapy and chemotherapy with 5FU and mitomycin-C. Chemoradiotherapy (CRT) achieves a good outcome for early stage tumors (T1-T2 tumors without nodal involvement), but more advanced tumors (T3-T4 or N1) are associated with a dismal prognosis. About 35 % of such patients relapse within two years after the end of treatment Recently, for metastatic or recurrent tumors after chemoradiotherapy, a chemotherapy combining docetaxel, cisplatin and 5FU (modified DCF protocol) has given very good results with a median overall survival of 39.2 months in 2 French trials (Epitopes HPV01 and 02). Our idea is to propose a new strategy , associating this chemotherapy (mDCF) followed by chemoradiotherapy to improve efficacy of the treatment for patients with locally advanced anal cancers. To this end, The principal investigator propose a national, multicenter, randomized phase 3 clinical trial to compare induction chemotherapy with mDCF followed by chemoradiotherapy versus standard chemoradiotherapy for locally advanced anal canal cancer.

the efficacy of the treatment will be evaluated by comparing disease-related event-free survival at 2 years according to the type of treatment. Other endpoints will also be evaluated such as overall survival and colostomy-free survival, treatment tolerability, response rate and quality of life.

This trial will be offered to patients over 18 years of age with locally advanced anal cancer without metastasis (T3-4 or N1). It is open to patients over 75 years of age subject to a favorable evaluation by an oncogeriatrician. It is also open to immunocompromised patients (HIV+) if their immunity is well controlled under antiretroviral treatment.The standard chemoradiotherapy treatment consists of 33 sessions of radiation, one session per day from Monday to Friday for 6.5 weeks. It is combined with chemotherapy that includes mitomycin during the first and fifth weeks of radiation therapy, as well as capecitabine that are taken on the days of radiation therapy.In the experimental arm, this chemoradiotherapy treatment is preceded by 4 sessions of mDCF chemotherapy performed every 2 weeks.After treatment, patients are followed up at 8 weeks, then every 4 months for 2 years, and every 6 months for the last year with clinical examination and imaging (CT and MRI).

Conditions

• Anal Cancer

Interventions

DRUG

induction chemotherapy (mDCF)

Induction chemotherapy consists of mDCF administered every 2 weeks: * Docetaxel (40 mg/m², day 1), * Cisplatin (40 mg/m², day 1) * 5-FU (1200 mg/m²/day IV for 2 days)

DRUG

Concomitant chemotherapy (Capecitabin + Mitomycin-C)

Concomitant Chemotherapy consists of Mitomycin-C (10 mg/m2 intravenous infusion at D1 and D29) and Capecitabine (1650 mg/m²/day divided in two oral intakes 825 mg/m² twice a day, five days a week). Patients should be counseled to only take capecitabine on the days when radiotherapy is being given

RADIATION

radiotherapy

Radiotherapy consists of conformational intensity-modulated external irradiation with simultaneous integrated boost (IMRT-SIB) with 2 level of dose (30 sessions) * 49.5 Gy (5 x 1.65 Gy/week) to the pelvis * 60 Gy (5 x 2 Gy /week) to the primary tumor and initially involved nodes

Sponsors & Collaborators

• Fondation ARCAD

  collaborator OTHER

• Federation Francophone de Cancerologie Digestive

  lead OTHER

Principal Investigators

• Veronique Vendrely, Md-pHD · University Hospital, Bordeaux

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-02-26

Primary Completion

2029-02-01

Completion

2030-02-01

Countries

• France
• Reunion

Study Locations