Inoperable œsophageal Cancer Clinical Trial
— CRUCIALOfficial title:
Phase II Trial in Inoperable œsophageal Cancer Evaluating the Feasibility of the Combination of Definitive Chemoradiation With the Immune Checkpoint Blockers Nivolumab +/- Ipilimumab
| Verified date | February 2023 |
| Source | European Organisation for Research and Treatment of Cancer - EORTC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The main objective of the trial is to assess the feasibility and the safety of the addition of immunotherapy with PD-1 antibody nivolumab +/- CTLA-4 antibody ipilimumab to concomitant chemoradiation therapy (CRT) in inoperable patients with early or locally advanced oesophageal cancer and to select the more promising experimental arm among the two possible combinations in terms of activity (based on progression free survival (PFS) at 12 months according to RECIST 1.1) for further evaluation in a phase III trial. The secondary objectives will aim to evaluate progression-free survival, failure-free survival and overall survival and pattern of progression (including incidence of distance metastasis).
| Status | Terminated |
| Enrollment | 8 |
| Est. completion date | October 7, 2022 |
| Est. primary completion date | October 7, 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Histologically proven oesophageal squamous cell carcinoma or adenocarcinoma - Both early stage and locally advanced tumor patients (according to TNM staging version 8): - T1, N1-3, M0 after complete work-up - T2, N0-3, M0 after complete work-up - T3, N0-3, M0 - Patient eligible for definitive chemoradiation and not considered for primary surgery after multidisciplinary meeting decision or patient refuses to undergo surgery - Subject must be previously untreated with systemic treatment given as primary therapy for advanced or metastatic disease - At least one measurable lesion by CT scan or MRI based on RECIST version 1.1 with radiographic tumor assessment performed within 28 days prior to randomization - Availability of adequate tissue in terms of quality and quantity for immunohistochemical staining for PDL-1 - WHO performance status 0 or 1 - Adequate organ function within 14 days prior to randomization Exclusion Criteria: - Cancer of cervical oesophagus (15 to 19 cm from dental ridge) - Known Her2 positive adenocarcinoma - Weight loss > 15 % over the last 3 months without improvement after nutritional support - Patient with cardiac dysfunction e.g. symptomatic congestive heart failure, uncontrolled hypertension - Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS), hepatitis B or hepatitis C. - Any prior treatment for advanced disease including treatment with an anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, anti-cytotoxic T lymphocyte associated antigen-4 (anti-CTLA-4) antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. - Live vaccines within 30 days prior to the first dose of study therapy. Examples of live vaccines include, but are not limited to the following: measles, mumps, rubella, chicken pox, yellow fever, H1N1 flu, rabies, BCG, and typhoid vaccine - History of hypersensitivity to study drugs or any excipient (refer to SmPCs for ipilimumab, nivolumab, 5-FU and oxaliplatin) - Current participation or treatment with an investigational agent or use of an investigational agent within 4 weeks of the first dose of study treatment - Serious comorbidity or life expectancy less than one year - Contraindication to chemoradiation therapy - Treatment history of radiotherapy - Child-Pugh B/C and patients with history of acute or chronic pancreatitis - Patient with Type I diabetes mellitus, or skin disorders - Known severe systemic autoimmune disease affecting the lungs or the bowel - Known contraindication to CT scans with IV contrast - Chronic use of immunosuppressive agents and/or systemic corticosteroids or any use in the last 15 days prior to enrollment - Active autoimmune disease that has required systemic treatment in past 2 years - Autoimmune paraneoplastic syndrome requiring immunosuppressive or dedicated treatment - History of any other hematologic or primary solid tumor malignancy, unless in remission for at least 5 years. |
| Country | Name | City | State |
|---|---|---|---|
| France | Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere | Paris | |
| France | Institut Gustave Roussy | Villejuif | |
| Spain | Hospital Del Mar | Barcelona | |
| Spain | Institut Catala d'Oncologia - ICO Badalona - Hospital De Mataro | Barcelona | |
| Spain | Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia) | Barcelona | |
| Spain | Hospital Universitario de Gran Canaria Doctor Negrin | Las Palmas De Gran Canaria | |
| Spain | Hospital Universitario 12 De Octubre | Madrid |
| Lead Sponsor | Collaborator |
|---|---|
| European Organisation for Research and Treatment of Cancer - EORTC |
France, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 12-Month Progression-free survival using RECIST 1.1 | The analysis of the 12-Month Progression-free survival rate (PFS-12) will be done when all patients achieved at least 15 months follow-up (12 months for the primary endpoint plus 100 days after the end of the protocol treatment). | 3.8 years from first patient in | |
| Secondary | Best overall response according to RECIST 1.1 | 3.8 years from first patient in | ||
| Secondary | Pattern of first cause of progression (either local relapse/progression,either regional relapse/progression, either distant metastasis) | 3.8 years from first patient in | ||
| Secondary | Progression-free survival using RECIST 1.1 | 3.8 years from first patient in | ||
| Secondary | Failure-free survival | 3.8 years from first patient in | ||
| Secondary | Overall survival | 3.8 years from first patient in | ||
| Secondary | Percentage of patients receiving the planned chemoradiation | 3.8 years from first patient in | ||
| Secondary | Relative dose intensity of oxaliplatinum | The dose intensity and relative dose intensity of treatments will be presented by drug and by treatment arm using median, range and interquartile range. | 3.8 years from first patient in | |
| Secondary | Relative dose intensity of 5FU | The dose intensity and relative dose intensity of treatments will be presented by drug and by treatment arm using median, range and interquartile range. | 3.8 years from first patient in |