DURVALUMAB for Unresectable oesophageal cancer | Oesophageal adenocarcinoma | Oesophageal squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- Histologically proven squamous cell carcinoma or adenocarcinoma of the oesophagus,\n- Unresectable disease due to anatomical consideration or medical condition, (patient unfit for surgical procedure),\n- Presence of at least one measurable lesion >10 mm with spiral CT scan,\n- No prior therapy for pathology investigated including chemotherapy or radiotherapy prior to the study, except anterior out of field radiotherapy, received for treatment of another primary tumor considered in remission in the past 5 years,\n- Age ≥18 years old,\n- WHO performance status <2 (i.e., 0 or 1),\n- Body weight >35 kg,\n- Life expectancy of at least 12 weeks ,\n- Adequate haematology laboratory data within the 7 days before randomization,\n- Adequate Biochemistry laboratory data within the 7 days before randomization,\n- Adequate haemostasis laboratory data within 7 days prior to randomization: prothrombin time (PT) within the normal range,\n- Adequate values for calcium, potassium and magnesium levels measured within 7 days prior to randomization,\n- Women should be post-menopaused or willing to accept the use an effective contraceptive regimen during the treatment period and for at least 6 months after the end of the study. All non-menopausal women should have a negative pregnancy test within 72 h prior to randomization. Men should accept to use an effective contraception during treatment period and at least 6 months after the end of the study especially after the last dose of oxaliplatin treatment.,\n- Patients must have provided consent for the study by signing and dating a written informed consent form prior to any study specific procedures, sampling, or analyses,\n- Patient affiliated to a social security regimen.,\n- Uracilemia < 16ng/ml,\n- Forced expiratory volume (FEV) >1 liter or > 50% of the theoretical value"}

Exclusion criteria

• {"criterion_text":"- Previous treatment with another PD-1, PD-L1 including durvalumab or CTLA-4 inhibitor\n- Metastatic disease,\n- Patients should not receive live vaccine 30 days prior to study drug\n- Female patients who are pregnant or breastfeeding\n- Uncontrolled intercurrent illness including, but not limited to diabetes, hypertension, pulmonary failure, chronic renal or hepatic diseases, active peptic ulcer disease or gastritis, active bleeding, diatheses... (non-exhaustive list),\n- Clinically significant cardiac disease or impaired cardiac function,\n- Current or prior use of immunosuppressive medication within 28 days before the first administration of durvalumab (exception: systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or equivalent are allowed as well as steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) - Topical, inhaled, nasal, and ophthalmic steroids are allowed,\n- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]).\n- Known primary immunodeficiency or active HIV,\n- Patient with a dihydropyrimidine dehydrogenase (DPD) deficiency (Uracilemia ≥ 16 ng/ml, the test should be done for all patients before 5-FU administration)* ,\n- Known active or chronic viral hepatitis or history of any type of hepatitis within the last 6 months indicated by positive HBS antibody test for hepatitis B or hepatitis C virus ribonucleic acid (HCV antibody),\n- History of organ transplantation requiring the use of immunosuppressive medication, including allogenic stem cell transplant,\n- History of active tuberculosis or latent disease capable of reactivation,\n- Current pneumonitis or interstitial lung disease,\n- Other invasive malignancy within 2 years prior to entry into the study, except for those treated with surgical therapy only,\n- History of severe allergic reactions or hypersensitivity to any unknown allergens or any components of the study drug (refer to IB of durvalumab section 5.5.1.11).\n- Any prior corticosteroid-refractory immune-related adverse event (irAE),\n- Oeso-tracheal or oeso-bronchial fistulae,\n- Major surgery within 28 days prior to the first dose of study treatment\n- Toxicities of grade ≥1 from any previous therapy\n- Peripheral sensory neuropathy with functional impairment\n- Severe infection requiring parenteral antibiotic treatment\n- Patients treated with sorivudine or analogues as brivudine\n- Patients treated with phenytoin for prophylaxis\n- Participation in another therapeutic trial within the 30 days prior to study inclusion,\n- Patients deprived of liberty or under guardianship,\n- Patients unable to adhere to the protocol for geographical, social, or psychological reasons."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is defined by a blinded independent centralized revue of progression free survival. cPFS is defined as the time from randomization until progression or death; patients alive and without documented progression at last follow-up news have PFS censored at this date or at initiation of new anticancer treatment (if applicable). Progression will be assessed by a blinded independent centralized revue of TDM per RECIST criteria 1.1","definition_or_measurement_approach":"cPFS defined as time from randomization until progression or death; progression assessed by blinded independent centralized review of CT scans (TDM) per RECIST v1.1. Patients alive without documented progression at last follow-up are censored at that date or at initiation of new anticancer treatment."}

Secondary endpoints

• {"endpoint_text":"- Progression-Free Survival (PFS) is defined as the time from randomization until progression or deaths; patients alive and without progression at last follow-up news are censored at this date.","definition_or_measurement_approach":"PFS: time from randomization to progression or death; censoring at last known progression-free date."}
• {"endpoint_text":"- Overall survival (OS): OS is defined by the delay between randomization and the occurrence of death due to any cause. Patients still alive at the time of analysis (including lost of follow-up) will be censored at the last known alive date.","definition_or_measurement_approach":"OS: time from randomization to death from any cause; censoring at last known alive date."}
• {"endpoint_text":"- Safety: safety will be assessed by the toxicity grading of the National Cancer Institute (NCI-CTCAE v 5.0, appendix 3). Adverse event (AE) occurrence will be detected by changes occurring in the course of treatment observed during clinical examination, in particular on vital signs (artery pressure, pulse, body temperature), in electrocardiogram (ECG) and biological tests (biochemistry, hematology). Use of concomitant treatments will be also taken into account.","definition_or_measurement_approach":"Safety measured by NCI-CTCAE v5.0 grading of adverse events; detection via clinical exam (vitals), ECG, laboratory tests (biochemistry, hematology) and recording concomitant treatments."}
• {"endpoint_text":"- Quality of life: Quality of life (QL) assessed by the European Organization for Research and Treatment of Cancer (EORTC) core QL questionnaire, the EORTC QLQ-C30 and Oes18 (Oesophageal Cancer Module).","definition_or_measurement_approach":"Quality of life assessed using EORTC QLQ-C30 and the Oes18 esophageal cancer module."}

France

Earliest CTIS Part Ii Submission Date

03-05-2024

Latest Decision Or Authorization Date

28-05-2024

Processing Time Days

25

Number Of Sites

23

Number Of Participants

120

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"AstraZeneca","duties_or_roles":"Source of monetary support","organisation_type":""}