Evaluation of Spartalizumab, Docetaxel, Cisplatin, and Fluorouracil with Radiotherapy in Metastatic Squamous Cell Anal Carcinoma: A Phase IIA Study
- Trial ID
- 2024-516005-23-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate the **Progression-Free Survival (PFS)** rate at 1 year in patients with metastatic squamous cell anal carcinoma. This measure is clinically relevant as it provides insight into the efficacy of the treatment regimen, which includes **spartalizumab**, mDCF (docetaxel, cisplatin, and 5-fluorouracil), and radiotherapy, in delaying disease progression. The study aims to determine the potential of this combination therapy to improve patient outcomes by extending the period during which the disease does not worsen.
Participants
The clinical trial focuses on individuals diagnosed with **metastatic squamous cell anal carcinoma**. The study population includes both male and female participants aged 18 years and older. Participants are required to have a performance status of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) criteria, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial does not involve a vulnerable population. Participants must have histologically confirmed metastatic or locally advanced recurrent squamous cell carcinoma of the anus, with an evaluable lesion as per RECIST v1.1 criteria. They should be eligible for the mDCF regimen and have not received prior systemic treatment, including immunotherapy or chemotherapy. Adequate organ and marrow function is necessary, as defined by specific laboratory criteria. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the trial details. Key inclusion criteria include a life expectancy of at least 12 months and the ability to comply with the study protocol. Participants must also be affiliated with or beneficiaries of the French social security system. The trial aims to evaluate the Progression-Free Survival (PFS) rate at 1 year.
Plans and Procedures
The clinical trial is designed to evaluate the **Progression-Free Survival** (PFS) rate at one year in patients with metastatic squamous cell anal carcinoma. This is a Phase IIA study employing a randomized, double-blind, controlled trial design. The trial is expected to run from June 2022 to June 2026, with participant involvement lasting up to 16 months. The study involves the administration of **spartalizumab**, **docetaxel**, **cisplatin**, **mitomycin**, and **fluorouracil**, all delivered via intravenous infusion, except for mitomycin, which is administered intravesically.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, performance status, and adequate organ function. The inclusion visit will also involve imaging assessments, including CT and PET scans, conducted within 30 days prior to inclusion. Following the screening, participants will attend regular follow-up visits to monitor treatment response and adverse events. The end-of-study visit will assess the primary endpoint, which is the PFS rate at one year, evaluated using RECIST criteria v1.1.
Participants are expected to remain in the study for the full duration unless specific conditions necessitate early termination. These conditions include significant adverse reactions, disease progression, or withdrawal of consent. The trial's primary endpoint is the PFS rate at one year, defined as the proportion of patients alive without progression at one year. The study aims to provide valuable insights into the efficacy of the treatment regimen in improving PFS in this patient population.
Treatment
**Docetaxel** is administered as a **solution for infusion** and is used in this clinical trial as an experimental medication. The active substance, docetaxel, is of chemical origin. The maximum daily dose is 40 mg/m², with a total maximum dose of 160 mg/m² over a treatment period of up to 12 weeks. The route of administration is **intravenous use**. Participant compliance is monitored through regular assessments of infusion administration and dosage adherence.
**Spartalizumab**, identified by the sponsor product code PDR001, is provided as a **concentrate for solution for infusion**. It is a protein-based substance and is administered intravenously. The maximum daily and total dose is 400 mg, with a treatment duration of up to 12 weeks. This investigational drug is produced by Novartis Pharma AG and is monitored for compliance through infusion records and participant follow-up.
**Cisplatin** is utilized as a **solution for infusion** in this study. The active substance, cisplatin, is chemically derived. The maximum total dose is 40 mg/m², administered over a period of up to 16 weeks. The administration route is via infusion, and compliance is ensured through scheduled dosing and monitoring of infusion sessions.
**Mitomycin** is administered as a **solution for intravesical use**. The active substance, mitomycin, is of chemical origin. The maximum total dose is 40 mg/m², with a treatment period extending up to 16 weeks. The administration is intravesical, and participant adherence is tracked through treatment logs and regular evaluations.
**Fluorouracil** is provided as a **solution for infusion**. The active substance, fluorouracil, is chemically based. The maximum total dose is 1200 mg/m², with a treatment duration of up to 16 weeks. The route of administration is via infusion, and compliance is monitored through infusion records and participant assessments.
Efficacy
The efficacy of the clinical trial will be assessed primarily through the evaluation of the **Progression-Free Survival (PFS)** rate at 1 year. This primary endpoint is defined as the proportion of patients who are alive without disease progression at the 1-year mark, as determined by the RECIST criteria version 1.1. The PFS rate will be calculated by dividing the number of patients who have not experienced disease progression by the total number of patients evaluable for PFS status at 1 year.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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
- No previous systemic (immunotherapy or chemotherapy) treatment.
- CT scan performed within 30 days prior inclusion,
- PET scan performed within 30 days prior inclusion
- 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: a. Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support. b. White blood cell count ≥ 2500/mm3 (≥ 2.5 GI/L). c. Platelets ≥ 100,000/mm3 (≥ 100 GI/L) without transfusion. d. Hemoglobin ≥ 9 g/dL (≥ 90 g/L). e. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN), or ≤ 5 x ULN with documented liver metastases. f. Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert’s disease ≤ 3 x ULN). g. Serum albumin ≥ 2.8 g/dl. h. Calculated creatinine clearance ≥ 60 mL/min (using the MDRD formula): i. Urine protein/creatinine ratio (UPCR) ≤ 1 g/g
- Signed and dated informed consent, to participate indicating that the subject has understood the purpose and the procedures required by the study and that he agrees to participate in the study and to comply with the requirements and restrictions inherent in this study
- Patient affiliated to or beneficiary of French social security system
- Ability to comply with the study protocol, in the Investigator’s judgment
Exclusion Criteria
- HIV positive patient , CD4 count < 400 cells/mm3 (HIV test mandatory before inclusion)
- Diagnosis of additional malignancy within 2 years prior to the inclusion with the exception for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy,
- Any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study,
- Current participation in a study of an investigational agent or in the period of exclusion,
- 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 7.5 months in women and 4.5 months in men 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
- Pre-existing neuropathy, hearing problem, or cardiorespiratory pathology, which prevent the administration of cisplatin.
- clinically significant active heart disease or myocardial infarction within 6 months
- recent or concomitant treatment with brivudine
- persistent toxicities related to prior treatment of grade greater than 1
- History or current interstitial lung disease or non-infectious pneumonitis
- History of major surgery within 28 days before treatment
- Active infection
- Active Hepatitis B infection (HBsAg positive)
- Active hepatitis C (HCV RNA positive)
- Pregnant or nursing (lactating) women confirmed by a positive hCG laboratory test within 72 hours prior to initiating study treatment. Note: Low levels of hCG may also be considered a tumor marker, therefore if low hCG levels are detected, another blood sample at least 4 days later must be taken to assess the kinetics of the increase and transvaginal ultrasound must be performed to rule out pregnancy.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 7.5 months after stopping treatment with Spartalizumab.
- Complete or partial deficit in dihydropyrimidine dehydrogenase (DPD) activity
- Active inflammatory bowel disease
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 09 Jun 2022 | 34 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
DOCETAXEL | Test | — | INTRAVENOUS USE | 40 | 12 | SUB12492MIG |
PDR001 | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 400 | 12 | PRD6759834 |
CISPLATIN | Other | — | SOLUTION FOR INFUSION | 0 | 16 | SUB07483MIG |
MITOMYCIN | Other | — | INTRAVESICAL USE | 0 | 16 | SUB09006MIG |
FLUOROURACIL | Test | — | SOLUTION FOR INFUSION | 0 | 16 | SUB07721MIG |