Informations générales (source: ClinicalTrials.gov)
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) (KANALRAD)
Interventional
Phase 3
Federation Francophone de Cancerologie Digestive (Voir sur ClinicalTrials)
février 2024
février 2030
05 avril 2025
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).
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 10/04/2025 13:12:06 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Jerome DURAND-LABRUNIE | 22/06/2024 21:11:02 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Pessac - Chu -Haut Leveque - Bordeaux - France | Véronique Vendrely, mdphd | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
1. Anal Squamous cell carcinoma histologically proven
2. Locally advanced tumors without metastases
- Stage T3 or T4
- Stage N1 (a, b or c) - any T (T1 to T4)
3. Age ≥18 and ≤ 75 or > 75 in case of score G8 > 14 or favourable oncogeriatric
assessment
4. Measurable tumor on MRI
5. Able to receive chemotherapy and radiotherapy
6. No major comorbidity that may preclude the delivery of treatment
7. Adequate hematologic function: absolute neutrophil count ≥ 1500/mm3, platelet count
≥ 100 000/mm3, Hb ≥ 9g/dl
8. Adequate renal function: creatinine clearance (according to MDRD formula) ≥ 60
ml/min
9. Adequate hepatic function: AST and ALT ≤ 2.5 × Upper Limit of Normal and total
bilirubin ≤ 1.5 × ULN
10. WHO performance status < 2
11. Signature of informed consent
12. A negative pregnancy test for inclusion in the study for all female patients of
child-bearing potential. In case of a "urine pregnancy test", it must be a highly
sensitive urine pregnancy test, in accordance with the recommendations of the CTFG
regarding pregnancy risk management (Recommendations related to contraception and
pregnancy testing in clinical trials)
13. 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)
14. Patient to be covered by a regimen of French Social Security system.
1. Anal Squamous cell carcinoma histologically proven
2. Locally advanced tumors without metastases
- Stage T3 or T4
- Stage N1 (a, b or c) - any T (T1 to T4)
3. Age ≥18 and ≤ 75 or > 75 in case of score G8 > 14 or favourable oncogeriatric
assessment
4. Measurable tumor on MRI
5. Able to receive chemotherapy and radiotherapy
6. No major comorbidity that may preclude the delivery of treatment
7. Adequate hematologic function: absolute neutrophil count ≥ 1500/mm3, platelet count
≥ 100 000/mm3, Hb ≥ 9g/dl
8. Adequate renal function: creatinine clearance (according to MDRD formula) ≥ 60
ml/min
9. Adequate hepatic function: AST and ALT ≤ 2.5 × Upper Limit of Normal and total
bilirubin ≤ 1.5 × ULN
10. WHO performance status < 2
11. Signature of informed consent
12. A negative pregnancy test for inclusion in the study for all female patients of
child-bearing potential. In case of a "urine pregnancy test", it must be a highly
sensitive urine pregnancy test, in accordance with the recommendations of the CTFG
regarding pregnancy risk management (Recommendations related to contraception and
pregnancy testing in clinical trials)
13. 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)
14. Patient to be covered by a regimen of French Social Security system.
1. Presence of metastases
2. Stage T1N0 or T2N0
3. History of pelvic radiotherapy
4. Complete or partial Dihydropyrimidine dehydrogenase (DPD) deficiency (uracilemia ≥
16 ng/mL)
5. Positive HIV serology with CD4 < 400 / mm3
6. Presence of neuropathy > grade 2 according to NCIC-CTC 4.0
7. Contraindication for chemotherapy and/or radiotherapy
8. Concomitant treatment with CYP3A4 inhibitors or inducers
9. Symptomatic cardiac or coronary insufficiency
10. Progressive active infection or any unbalanced progressive severe condition in the
last 6 months
11. No contraindication to MRI imaging
12. 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
13. breastfeeding woman.
14. Persons deprived of liberty or under guardianship or incapable of giving consent
15. Any psychological, familial, sociological, or geographical condition potentially
hampering compliance with the study protocol or follow-up schedule.
16. Live attenuated vaccines within 4 weeks before randomization 17. In case of hearing
problem 18. In case of combination with phenytoin with prophylactic aim 19. In case
of recent or concomitant treatment brivudine