Phase III Study Evaluating Induction Chemotherapy Followed by Chemoradiotherapy Compared to Standard Chemoradiotherapy for Locally Advanced SCCA
KANALRAD
PRODIGE 85- KANALRAD : Prospective Randomized Phase III Study Evaluating Induction Chemotherapy (Modified DCF 4 Cycles) Followed by Chemoradiotherapy Compared to Standard Chemoradiotherapy for Locally Advanced Anal Squamous Cell Carcinoma (T3-4 or N1a, b or c)
1 other identifier
interventional
310
2 countries
114
Brief 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Feb 2024
Longer than P75 for phase_3
114 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 5, 2024
CompletedFirst Posted
Study publicly available on registry
January 17, 2024
CompletedStudy Start
First participant enrolled
February 26, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 1, 2030
September 2, 2025
February 1, 2025
4.9 years
January 5, 2024
August 29, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Disease-related event free survival (DREFS) at 2 years
DREFS will be compared between the two arms . An event is defined as :progression, residual tumor at 6 months requiring APR, recurrence (local or metastatic) or death
2 years after last patient completed treatment
Study Arms (2)
Control arm
ACTIVE COMPARATORPelvic chemoradiotherapy 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 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
Exeprimental arm
EXPERIMENTALInduction chemotherapy with mDCF (4 cycles) followed by pelvic chemoradiotherapy 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) Chemoradiotherapy is the same as described above in control arm
Interventions
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)
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
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
Eligibility Criteria
You may qualify if:
- Anal Squamous cell carcinoma histologically proven
- Locally advanced tumors without metastases
- Stage T3 or T4
- Stage N1 (a, b or c) - any T (T1 to T4)
- Age ≥18 and ≤ 75 or \> 75 in case of score G8 \> 14 or favourable oncogeriatric assessment
- Measurable tumor on MRI
- Able to receive chemotherapy and radiotherapy
- No major comorbidity that may preclude the delivery of treatment
- Adequate hematologic function: absolute neutrophil count ≥ 1500/mm3, platelet count ≥ 100 000/mm3, Hb ≥ 9g/dl
- Adequate renal function: creatinine clearance (according to MDRD formula) ≥ 60 ml/min
- Adequate hepatic function: AST and ALT ≤ 2.5 × Upper Limit of Normal and total bilirubin ≤ 1.5 × ULN
- WHO performance status \< 2
- Signature of informed consent
- Female patients postmenopausal for at least one year or surgically infertile for at least 6 weeks, or effective contraception for male (until 6 months after the end of the investigational treatments) and female patients of childbearing potential (until 7.5 months after the end of treatment with cisplatine)
- Patient to be covered by a regimen of French Social Security system.
You may not qualify if:
- Presence of metastases
- Stage T1N0 or T2N0
- History of pelvic radiotherapy
- Complete or partial Dihydropyrimidine dehydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)
- Positive HIV serology with CD4 \< 400 / mm3
- Presence of neuropathy \> grade 2 according to NCIC-CTC 4.0
- Contraindication for chemotherapy and/or radiotherapy
- Concomitant treatment with CYP3A4 inhibitors or inducers
- Symptomatic cardiac or coronary insufficiency
- Progressive active infection or any unbalanced progressive severe condition in the last 6 months
- No contraindication to MRI imaging
- Other cancer treated within the last 3 years except in situ cervical carcinoma or basocellular/ spinocellular carcinoma or any other carcinoma in situ considered as cured
- breastfeeding woman.
- Persons deprived of liberty or under guardianship or incapable of giving consent
- Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol or follow-up schedule.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Federation Francophone de Cancerologie Digestivelead
- Fondation ARCADcollaborator
Study Sites (114)
AGEN-Cromg
Agen, France
Clinique Calabet
Agen, France
AIX EN PROVENCE CH Pays d'Aix
Aix-en-Provence, France
Amiens - Clinique de L'Europe
Amiens, France
ANTONY Hôpital Privé
Antony, France
Argenteuil - Ch
Argenteuil, France
ARRAS Les Bonnettes
Arras, France
ARRAS Marie Curie
Arras, France
AURILLAC-Henri Mondor
Aurillac, France
Centre Medico Chirurgical
Aurillac, France
AUXERRE CH GHT Unyon
Auxerre, France
Avignon Icap
Avignon, France
Avranches - Hopital Prive de La Baie
Avranches, France
Bayonne- Clinique Belharra
Bayonne, France
BEAUVAIS-Simone Veil
Beauvais, France
Besancon Chu
Besançon, France
Beuvry - Clinique Ambroise Pare
Beuvry, France
Beuvry Pierre Curie
Beuvry, France
Bordeaux - Privé - Tivoli
Bordeaux, France
BORDEAUX-Institut Bergonié
Bordeaux, France
Institut Bergonié
Bordeaux, France
Pessac - Chu -Haut Leveque
Bordeaux, France
Ch Duchenne
Boulogne-sur-Mer, France
BREST Pasteur Lanroze
Brest, France
CAEN Polyclinique du Parc
Caen, France
CAEN-François Baclesse
Caen, France
Cahors -Ch
Cahors, France
Caluire Et Cuire-Infirmerie Protestante
Caluire-et-Cuire, France
Chalon-Sur-Saone Hopital Sainte Marie
Chalon-sur-Saône, France
Chambery Ch
Chambéry, France
Chambray Les Tours-Roc37
Chambray-lès-Tours, France
Centre Jean Perrin
Clermont-Ferrand, France
Chu Estaing
Clermont-Ferrand, France
Centre de Radiothérapie Savoie Nord
Contamine-sur-Arve, France
Clinique de Flandre
Coudekerque-Branche, France
CRETEIL-Henri Mondor CHU
Créteil, France
DAX CH
Dax, France
DECHY-Léonard de Vinci
Dechy, France
Dijon - Chu François Mitterrand
Dijon, France
DIJON-GF Leclerc
Dijon, France
DIJON-Institut de Cancérologie de Bourgogne
Dijon, France
Ghm Grenoble - Institut Daniel Hollard
Grenoble, France
LA ROCHE-SUR-YON CHD Vendée
La Roche-sur-Yon, France
Guillaume Le Conquérant
Le Havre, France
LE HAVRE-l'Estuaire
Le Havre, France
LE MANS-CH Victor Hugo
Le Mans, France
Lille - Hopital Prive La Louviere
Lille, France
Limoges - Polyclinique Francois Chenieux
Limoges, France
Limoges-Chu Dupuytren
Limoges, France
LONGJUMEAU-GHNE Hôpital d'Antony
Longjumeau, France
Lorient - Groupe Hospitalier Bretagne Sud - Site Du Scorff
Lorient, France
LYON Jean Mermoz
Lyon, France
LYON- Léon Bérard
Lyon, France
LYON-Saint Joseph
Lyon, France
MARSEILLE Institut Paoli Calmettes
Marseille, France
MARSEILLE Saint-Joseph
Marseille, France
MARSEILLE-Hôpital la Timone
Marseille, France
Montbeliard Ch
Montbéliard, France
MONTPELLIER-ICM Val d'Aurelle
Montpellier, France
Mougins Cac
Mougins, France
MULHOUSE CH Emile Muller
Mulhouse, France
Nantes - Hopital Prive Du Confluent
Nantes, France
NEUILLY-SUR-SEINE GH Hartmann
Neuilly-sur-Seine, France
NICE-Antoine LACASSAGNE
Nice, France
Centre Hospitalier
Niort, France
Nimes Chu
Nîmes, France
ORLEANS Centre Hospitalier Régional
Orléans, France
OSNY-CHP Sainte-Marie
Osny, France
Paris - Ap-Hp - Hopital Tenon
Paris, France
Paris - Chu -Saint Louis Aphp
Paris, France
PARIS GHD Croix Saint-Simon
Paris, France
PARIS Hopital Europeen Georges-Pompidou
Paris, France
PARIS Institut Curie
Paris, France
PARIS-Saint Joseph
Paris, France
Pau Groupe de Radiotherapie Et D'Oncologie Des Pyrenees
Pau, France
PERIGUEUX-Hôpital Francheville
Périgueux, France
Plerin Hopital Prive Des Cotes D'Armor - Centre Cario
Plérin, France
POITIERS- CHU la Miletrie
Poitiers, France
PRINGY-Annecy Genevois CH
Pringy, France
REIMS-CHU Robert Debré
Reims, France
REIMS-Jean Godinot
Reims, France
Rennes - Centre Eugene Marquis
Rennes, France
Rennes Chu Pontchaillou
Rennes, France
RODEZ CH
Rodez, France
Hopitaux Prives Rouennais - Clinique Mathilde
Rouen, France
ROUEN-Frédéric Joliot
Rouen, France
Saint Denis Ch
Saint-Denis, France
CHU
Saint-Etienne, France
Saint Herblain Ico
Saint-Herblain, France
SAINT NAZAIRE CM l'Estuaire
Saint-Nazaire, France
Centre Hospitalier
Saint-Quentin, France
SARCELLES - Institut de Cancérologie Paris Nord
Sarcelles, France
Clinique Cote d'Emeraude
St-Malo, France
Saint Malo Ch
St-Malo, France
Strasbourg Icans
Strasbourg, France
STRASBOURG Sainte Anne
Strasbourg, France
Tarbes - Lourdes - Ch
Tarbes, France
Tarbes - Polyclinique de L'Ormeau
Tarbes, France
Thonon Les Bains - Hopitaux Du Leman
Thonon-les-Bains, France
Centre de Radiothérapie Saint-Louis
Toulon, France
TOULON-Sainte Anne
Toulon, France
Toulouse - Oncopole Institut Claudius Regaud
Toulouse, France
Toulouse Chu - Hopital Rangueil
Toulouse, France
TOULOUSE-Clinique Pasteur
Toulouse, France
TOURS CHU Trousseau
Tours, France
Valence - Centre Marie Curie
Valence, France
Valence Ch
Valence, France
VALENCE Drôme-Ardèche
Valence, France
Vandoeuvre Les Nancy-Ic Lorraine
Vandœuvre-lès-Nancy, France
VILLEJUIF Gustave Roussy
Villejuif, France
Centre de Radiothérapie Bayard
Villeurbanne, France
Villeurbanne Medipole Hopital Mutualiste Lyon
Villeurbanne, France
Reunion - Chu Sud
Saint-Pierre, Reunion
La Reunion - Clinique Prive Sainte Clotilde
Sainte-Clotilde, Reunion
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Veronique Vendrely, Md-pHD
University Hospital, Bordeaux
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 5, 2024
First Posted
January 17, 2024
Study Start
February 26, 2024
Primary Completion (Estimated)
February 1, 2029
Study Completion (Estimated)
February 1, 2030
Last Updated
September 2, 2025
Record last verified: 2025-02