Combination of Spartalizumab, mDCF and Radiotherapy in Patients With Metastatic Squamous Cell Anal Carcinoma

NCT04894370 | Recruiting Phase 2 DMC

• 1 other identifier: 2020/538
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 5

Brief Summary

This study evaluates the feasibility of the combination of radiotherapy, chemotherapies (docetaxel, cisplatin and 5-fluorouracil) and spartalizumab (anti-PD-1 therapy) in patients with metastatic squamous cell anal carcinoma

Conditions

Squamous Cell Anal Carcinoma; Metastatic Squamous Cell Carcinoma

Keywords

immunotherapy; chemotherapy; radiotherapy; anti-PD1

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) rate at 1 year.

  PFS rate at 1 year is defined as the number of patients alive without progression at 1 year divided by the overall number of patients evaluable for PFS status at 1 year. A patient is evaluable for PFS status at 1 year if he dies during the 1 year of follow up or if he is alive with a RECIST evaluation available at 1 year.

  12 months from enrollment

Secondary Outcomes (3)

• Objective response rate (ORR)

  12 months from enrollment

• Overall survival (OS)

  through study completion, an average of 3 years

• Progression-Free Survival (PFS) median.

  through study completion, an average of 3 years

Study Arms (1)

Experimental

EXPERIMENTAL

Phase 1: Radiotherapy (8 Gy on target lesions) Phase 2: Combination immunotherapy and mDCF regimen mDCF regimen every 2 weeks for 8 cycles * Docetaxel (40 mg/m², day 1), * Cisplatin (40 mg/m², day 1) * 5-FU (1200 mg/m²/day for 2 days) Spartalizumab: 400 mg intravenous will be administrated every 4 weeks Phase 3 : Multimodal treatment of residual disease The multimodal treatment is recommended in oligometastatic anal cancer. The support by ablative treatment (surgery, hypofractionnated radiotherapy or by radiofrequency) improve survival. In absence of progression disease: * Ablative treatment: surgery, hypofractionnated radiotherapy or by radiofrequency of residual metastases * and Chemo-radiotherapy (CRT) for local disease Phase 4: Maintenance treatment with Spartalizumab 400 mg intravenous every 4 weeks for 12 months from enrolment maximum

Biological: Sample collection

Interventions

Sample collection BIOLOGICAL

PBMC collection at baseline, after radiotherapy 8 Gy (gray), at 6 months and at 12 months from inclusion: 6 EDTA tubes of 6 ml of peripheral blood mononuclear cell \[PBMC\] will be sent to the central laboratory (Biomonitoring Platform of Besançon, CHRU de Besançon located at Etablissement Français du Sang) at room temperature within 24 hours via an approved carrier for their processing, storage and immunomonitoring analysis. A sending sheet of the samples will be attached to each single sample. Plasma collection at baseline, after radiotherapy 8 Gy, at 6 months and at 12 months from inclusion: One 6 ml EDTA tube should be frozen in each investigation center for plasma collection. Plasma for circulating tumoral DNA (ctDNA) collection at baseline, at 2, 6 and 12 months from inclusion: two EDTA tube of 4 ml should be frozen in each investigation center for ctDNA collection.

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged ≥18 years,
• Performance status Eastern Cooperative Oncology Group World Health Organization (ECOG-WHO) ≤1,
• Histologically proven metastatic or locally advanced recurrent squamous cell carcinoma of anus (SCCA)
• Presence of a evaluable lesion on CT-scan/MRI assessed by RECIST v1.1 criteria,
• Patient eligible to the mDCF regimen
• Life expectancy ≥12 months,
• Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
• Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support.
• White blood cell count ≥ 2500/mm3 (≥ 2.5 GI/L).
• Platelets ≥ 100,000/mm3 (≥ 100 GI/L) without transfusion.
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN), or ≤ 5 x ULN with documented liver metastases.
• Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN).
• Serum albumin ≥ 2.8 g/dl.
• Calculated creatinine clearance ≥ 60 mL/min (using the MDRD formula):

You may not qualify if:

• Any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study,
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment,
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible,
• Pregnancy, breast-feeding or absence/refusal of adequate contraception for fertile patients during the period of treatment and for 6 months from the last treatment administration,
• Patient under guardianship, curatorship or under the protection of justice.
• Inability to perform radiotherapy
• Untreated or symptomatic central nervous system (CNS) lesion. However, patients are eligible if: a) all known CNS lesions have been treated with radiotherapy or surgery and b) patient remained without evidence of CNS disease progression ≥ 4 weeks after treatment and c) patients must be off corticosteroid therapy for ≥ 2 weeks
• Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF, M-CSF), thrombopoietin mimetics or erythroid stimulating agents ≤ 2 weeks prior start of study treatment. If erythroid stimulating agents were initiated more than 2 weeks prior to the first dose of study treatment and the patient is on a stable dose, they can be maintained.
• Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment
• Elevated Cardiac troponin T (cTnT) or cardiac troponin I (cTnI) elevation \> 2x ULN
• Systemic chronic steroid therapy (\> 10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date of first dose of study treatment.
• Note: Topical, inhaled, nasal and ophthalmic steroids are allowed. For patients with adrenal insufficiency, replacement dose of prednisone \> 10 mg/ day or equivalent are permitted
• Active, known or suspected autoimmune disease or a documented history of autoimmune disease Note: Patients with vitiligo, controlled type I diabetes mellitus on stable insulin dose, residual autoimmune-related hypothyroidism only requiring hormone replacement or psoriasis not requiring systemic treatment are permitted.
• Allogenic bone marrow or solid organ transplant
• History of severe hypersensitivity reactions to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead
• National Cancer Institute, France: collaborator
• Novartis: collaborator

Study Sites (5)

Centre Hospitalier Universitaire de Besançon

Besançon, 25000, France

RECRUITING

Centre Georges-François Leclerc (CGFL)

Dijon, France

RECRUITING

Hôpital Franco-Britannique

Levallois-Perret, France

WITHDRAWN

Centre Léon Bérard

Lyon, 69000, France

WITHDRAWN

Hôpital Nord Franche Comté

Montbéliard, France

RECRUITING

Related Publications (3)

• Kim S, Francois E, Andre T, Samalin E, Jary M, El Hajbi F, Baba-Hamed N, Pernot S, Kaminsky MC, Bouche O, Desrame J, Zoubir M, Ghiringhelli F, Parzy A, De La Fouchardiere C, Smith D, Deberne M, Spehner L, Badet N, Adotevi O, Anota A, Meurisse A, Vernerey D, Taieb J, Vendrely V, Buecher B, Borg C. Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (Epitopes-HPV02): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2018 Aug;19(8):1094-1106. doi: 10.1016/S1470-2045(18)30321-8. Epub 2018 Jul 2.

  PMID: 30042063 BACKGROUND

• Kim S, Meurisse A, Spehner L, Stouvenot M, Francois E, Buecher B, Andre T, Samalin E, Jary M, Nguyen T, El Hajbi F, Baba-Hamed N, Pernot S, Kaminsky MC, Bouche O, Desrame J, Zoubir M, Ghiringhelli F, Parzy A, de la Fouchardiere C, Boulbair F, Lakkis Z, Klajer E, Jacquin M, Taieb J, Vendrely V, Vernerey D, Borg C. Pooled analysis of 115 patients from updated data of Epitopes-HPV01 and Epitopes-HPV02 studies in first-line advanced anal squamous cell carcinoma. Ther Adv Med Oncol. 2020 Dec 4;12:1758835920975356. doi: 10.1177/1758835920975356. eCollection 2020.

  PMID: 33329760 BACKGROUND

• Kim S, Buecher B, Andre T, Jary M, Bidard FC, Ghiringhelli F, Francois E, Taieb J, Smith D, de la Fouchardiere C, Desrame J, Samalin E, Parzy A, Baba-Hamed N, Bouche O, Tougeron D, Dahan L, El Hajbi F, Jacquin M, Rebucci-Peixoto M, Spehner L, Vendrely V, Vernerey D, Borg C. Atezolizumab plus modified docetaxel-cisplatin-5-fluorouracil (mDCF) regimen versus mDCF in patients with metastatic or unresectable locally advanced recurrent anal squamous cell carcinoma: a randomized, non-comparative phase II SCARCE GERCOR trial. BMC Cancer. 2020 Apr 25;20(1):352. doi: 10.1186/s12885-020-06841-1.

  PMID: 32334548 BACKGROUND

MeSH Terms

Conditions

Anus Neoplasms; Carcinoma, Squamous Cell

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Central Study Contacts

Stefano KIM, Pr

CONTACT

+33 (0)3 81 47 99 99; stefanokim@gmail.com

Christophe BORG, Pr

CONTACT

+33 (0)3 81 47 99 99; christophe.borg@efs.sante.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: May 20, 2021
• Study Start: June 9, 2022
• Primary Completion: June 1, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 22, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)