Clinical Trials Logo

Clinical Trial Summary

The RADIANCE multicenter, randomized phase II trial will assess the efficacy of durvalumab, a PD-L1 immune checkpoint inhibitor, in combination with primary mitomycin C (MMC)/5-fluorouracil (5-FU)-based radiochemotherapy (RCT) in patients with locally-advanced anal squamous cell carcinoma (ASCC).


Clinical Trial Description

Anal squamous cell carcinomas (ASCC) are increasing in frequency across the developed world. There is a strong rationale for combining the PD-L1 immune checkpoint inhibitor durvalumab with radiochemotherapy (RCT) in patients with ASCC. First, although primary RCT with concurrent mitomycin C and 5-fluorouracil (MMC/5-FU) is the standard treatment for ASCC, the 3-year DFS in patients with locally-advanced disease is only in the range of 60%. Second, approximately 80-90% of patients with ASCC are human papilloma virus (HPV)-positive, which is associated with higher tumor "immunogenicity" in this malignancy that is known to correlate with better response to RCT as well as PD-1/PD-L1 immune checkpoint inhibitors. Also, PD-L1 expression was observed in 33%-62% of patients with locally advanced non-metastatic ASCC that correlated with tumor stage. Third, inhibition of the PD-1/PD-L1 axis showed encouraging responses in recurrent/metastatic ASCC in two phase Ib/II trials. Fourth, several data indicate complementary roles between R(C)T and immunotherapy. Fifth, R(C)T can induce PD-L1 upregulation with resulting dysfunction in CD8+ T-cells, and addition of anti-PD-L1 to R(C)T can overcome T-cell suppression to reinvigorate immune surveillance. First clinical studies have demonstrated promising findings for the combination of RCT and immunotherapies. Thus, based on the above data, RCT combined with durvalumab is expected to be more effective than primary RCT alone. Altogether, the hereby proposed RADIANCE multicenter, randomized phase II trial aims to improve the current standard treatment by incorporating durvalumab to the primary MMC/5-FU-based RCT in patients with locally-advanced ASCC (T2=>4cm Nany, stage IIB-IIIC). ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04230759
Study type Interventional
Source Goethe University
Contact
Status Active, not recruiting
Phase Phase 2
Start date January 7, 2020
Completion date March 31, 2027

See also
  Status Clinical Trial Phase
Enrolling by invitation NCT05060471 - PD-1 Blockade Combined With Chemotherapy Followed by Concurrent Immunoradiotherapy for Locally Advanced SCCA Patients Phase 2
Active, not recruiting NCT02135419 - Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Lesions Phase 3
Completed NCT05518201 - Evaluate the Safety and Immunogenicity of a 9-valent HPV Vaccine in Chinese Healthy Male Aged 9-45 Year-old Phase 1
Withdrawn NCT02857608 - A Prospective, Open-Label, Multi-center Comparison of Lymphoseek Identified Lymph Nodes and Clinically Identified Lymph Nodes of Subjects With Known Cancer of the Anus Phase 2
Active, not recruiting NCT02546973 - Quality of Life in Patients With Anal Cancer
Terminated NCT00903396 - Palonosetron Hydrochloride in Preventing Nausea and Vomiting Caused by Radiation Therapy in Patients With Primary Abdominal Cancer Phase 2
Terminated NCT00896467 - Psychological and Emotional Impact in Patients Undergoing Treatment For Metastatic Cancer Either in a Clinical Trial or as Standard Off-Trial Therapy N/A
Completed NCT00550589 - Cidofovir in Treating HIV-Infected Patients With High-Grade Squamous Intraepithelial Lesions of the Skin Near the Anus Phase 2
Completed NCT00324415 - Combined Modality Therapy for Patients With With HIV and Stage I, Stage II, or Stage III Anal Cancer Phase 2
Terminated NCT00568425 - QOL & Functional Outcomes After Combined Modality Tx for Anal CA: Comparison of Conventional vs IMRT
Terminated NCT00267787 - Molecular Genetic and Pathological Studies of Anal Tumors
Completed NCT00066430 - Infrared Coagulation in Preventing Anal Cancer in Patients With HIV Who Have Anal Neoplasia Phase 1
Completed NCT04083053 - High-Resolution Anoscopy Perceived Discomfort Study N/A
Completed NCT03506529 - Identification of Predictive Factors for Physiological Hypermetabolism of the Anal Canal in 18F-FDG PET / CT
Recruiting NCT05835947 - Anal Cancer Risk In Women
Not yet recruiting NCT03947775 - HPV-SAVE_Merck_Sub-Study for Preventing Recurrence of HSIL Phase 2
Recruiting NCT04857528 - Detecting HPV DNA in Anal and Cervical Cancers
Recruiting NCT04708470 - A Phase I/II Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies, Small Bowel, and Colon Cancers Phase 1/Phase 2
Recruiting NCT04907643 - Virtual Reality for GI Cancer Pain to Improve Patient Reported Outcomes N/A
Active, not recruiting NCT01937780 - Anal Cancer Radiotherapy Study