NIVOLUMAB for Esophageal cancer | Adenocarcinoma of the esophagus or gastroesophageal junction | Squamous cell carcinoma of the esophagus

Inclusion criteria

• {"criterion_text":"- Age > 18 years\n- Specific inclusion criteria - Cohort A: 1. Eligible for palliative fractionated radiotherapy of the esophageal- or gastroesophageal cancer as determined by the multidisciplinary team (MDT) meeting. 2. Expected survival >3 months. 3. Not bulky disease, i.e. palliative radiotherapy towards the primary tumor is intended to palliate dysphagia and/or pain and systemic treatment could be delayed to AFTER protocol therapy if possible.\n- Specific inclusion criteria – Cohort B: 1. Eligible for definitive chemoradiation of localized but inoperable esophageal- or gastroesophageal cancer as determined by the multidisciplinary team (MDT) meeting. 2. Regional disease, i.e. no metastasis outside the radiation field (PTV). 3. Considered candidate/ able to adhere to the intended chemoradiotherapy\n- Specific inclusion criteria – Cohort C: 1. Eligible for neoadjuvant chemoradiotherapy and surgery of the esophageal- or gastroesophageal cancer as determined by the multidisciplinary team (MDT) meeting. 2. Regional disease, i.e. no metastasis outside the radiation field (PTV). 3. Considered candidate and able to adhere to the intended neoadjuvant chemoradiotherapy and planned surgery.\n- Patients should have previously untreated histologically proven squamous cell carcinoma or adenocarcinoma of the esophagus or the gastroesophageal junction (GEJ), Siewert I, II or III\n- Must be ambulatory with a performance status ECOG 0 or 1\n- Adequate organ function based on clinical examiniation and lab values as defined in the below: Absolute neutrophil count: ≥ 1,5 x109/L Platelets: ≥ 100 x109/L Hemoglobin: ≥ 9 x109/L Creatinine ≤ 1,5 upper limit normal (ULN) OR measured/calculaterd GFR≥60 mL/min Albumin ≥ 30 g/L Total bilirubin ≤ 1,5 ULN ASAT and ALAT ≤ 2,5 ULN, or ≤ 5 ULN for subjects with liver mets. International Normalized Ratio (INR) ≤ 1,5 ULN and Activated Partial Thromboplastin Time (TT) ≤ 1,5 ULN unless subject is receiving anticoagulant therapy. Such therapy (if indicated) should be converted to adequate therapy with low-molecular weight heparin such as Dalteparin before chemotherapy or treatment with IMP.\n- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 28 days prior to the start of study drug (screening phase). Women must not be breastfeeding.\n- WOCBP should use highly effective adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for Nivolumab to undergo five half-lives) after the last dose of investigational drug. Adequate methods are described in Appendix I.\n- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception during the study treatment period and until 7 months after last dose of Nivolumab\n- Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.\n- If Dysphagia score >2, a nasogastric feeding tube should be inserted during the aid of gastroscopy, and nasogastric tube feeding started before radiotherapy."}

Exclusion criteria

• {"criterion_text":"- Previous treatment with radiotherapy towards volumes within the thoracic cavity\n- History of prior malignancy within the last 5 years, excluding curatively treated basal cell or squamous cell carcinoma of the skin.\n- Known history of brain metastases\n- Need to use immunosuppressive drugs including, but not limited to: Glukocorticoids, everolimus, sirolimus, disease-modifying anti-rheumatic drugs (DMARDS)\n- Positive pregnancy test (positive hCG blood test)\n- Known allergy, hypersensitivity, or contraindication to the investigational product Nivolumab, or the drugs paclitaxel and docetaxel used in the standard chemoradiotherapy protocols (Cohorts B and C) or any components used in their preparation or has a contraindication to taxane therapy.\n- Any reason why, in the opinion of the investigator, the patient should not participate.\n- Previous treatment with any PD-1 or PD-L1/2 inhibitor\n- Hypersensitivity to the investigational product or any of the drug formula contents\n- Esophageal stenting\n- T4b if infiltration into the aorta or the trachea\n- History of prior autoimmune disorders requiring systemic therapy (excluding Insulin or Thyroid replacement therapy)\n- History of HIV 1 /2, Hepatitis B or C infection\n- History of Immunodeficiency disorders (i.e. immunoglobulin deficiency or white blood cell lineage depletion disorders)\n- Participation in any other interventional clinical trial with an investigational product"}

Primary endpoints

• {"endpoint_text":"- Safety: The primary end point in this study is safety measurements done to determine the safety profile of the treatment; safety parameters included adverse events, biochemistry, hematology, vital signs and performance status. Adverse events are recorded according to CTCAE v5.0 (CTCAE grade 2-5 rate).","definition_or_measurement_approach":"Safety parameters: adverse events, biochemistry, hematology, vital signs and performance status. Adverse events recorded according to CTCAE v5.0 (CTCAE grade 2-5 rate)."}
• {"endpoint_text":"- Feasibility: The feasibility of conducting the study will be reported as number of patients screened, and number of patients successfully included into the study per one year of accrual time.","definition_or_measurement_approach":"Feasibility measured as number of patients screened and number of patients successfully included into the study per one year of accrual time."}

Secondary endpoints

• {"endpoint_text":"- Overall Survival: The time from onset of treatment (day 1) to death from any cause.","definition_or_measurement_approach":"Measured from onset of treatment (day 1) to death from any cause."}
• {"endpoint_text":"- Infield and Outfield Response to Treatment: The response rate as measured by RECIST 1.1 and immune-related RECIST (ir-RECIST) within the irradiated volume (infield) verses outside the irradiated volume (outfield).","definition_or_measurement_approach":"Response rates assessed by RECIST v1.1 and ir-RECIST for infield (irradiated volume) vs outfield (outside irradiated volume)."}
• {"endpoint_text":"- Progression Free Survival (Only Cohort B): The time from treatment start (day -21) until the disease progresses (PD) as determined by investigators from tumor assessments per RECIST or death from any cause.","definition_or_measurement_approach":"Measured from treatment start to documented progression per RECIST or death; applies to Cohort B only."}
• {"endpoint_text":"- Disease Free Survival (Only Cohort C): The time from surgery until recurrency or occurrence of disease progression as determined by investigators from tumor assessments per RECIST.","definition_or_measurement_approach":"Measured from date of surgery to recurrence or disease progression per RECIST; applies to Cohort C only."}
• {"endpoint_text":"- Pathology Complete Response Rate (Only Cohort C): The complete response rate in the surgical specimen by Chirieac grading by pathologist.","definition_or_measurement_approach":"Assessed on surgical specimen using Chirieac grading by pathologist; applies to Cohort C only."}
• {"endpoint_text":"- Quality of Life:Quality of Life Questionnaires (QLQ) by patient reported outcomes EORTC QLQ-C30, EORTC QLQ-OG25 and EQ-5D.","definition_or_measurement_approach":"Patient-reported QOL using EORTC QLQ-C30, EORTC QLQ-OG25 and EQ-5D instruments."}

Norway

Earliest CTIS Part Ii Submission Date

09-09-2024

Latest Decision Or Authorization Date

19-12-2025

Processing Time Days

466

Number Of Sites

1

Number Of Participants

30

Primary sponsor

Full Name

Oslo University Hospital HF

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway