- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03437200
Combination of Chemoradiation With Immunotherapy in Inoperable œsophageal Cancer (CRUCIAL)
Phase II Trial in Inoperable œsophageal Cancer Evaluating the Feasibility of the Combination of Definitive Chemoradiation With the Immune Checkpoint Blockers Nivolumab +/- Ipilimumab
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).
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: EORTC HQ
- Phone Number: +32 2 7744 1611
- Email: 1714@gmail.com
Study Locations
-
-
-
Paris, France, 75651
- Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere
-
Villejuif, France, 94805
- Institut Gustave Roussy
-
-
-
-
-
Barcelona, Spain, 08003
- Hospital del Mar
-
Barcelona, Spain, 08908
- Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)
-
Barcelona, Spain, 08304
- Institut Catala d'Oncologia - ICO Badalona - Hospital De Mataro
-
Las Palmas De Gran Canaria, Spain, 35019
- Hospital Universitario de Gran Canaria Doctor Negrin
-
Madrid, Spain, 28041
- Hospital Universitario 12 de octubre
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A: Chemoradiation + Nivolumab
All patients will receive standard fractionation radiation therapy (RT) scheme: 50Gy in 25 fractions over 5 weeks (i.e. 2Gy per fraction), concurrently with 3 cycles of 2 weeks of FOLFOX followed by 3 cycles of 2 weeks of FOLFOX without RT. Induction phase: Nivolumab IV 240 mg on days 1, 15 and 29 followed by a maintenance phase (to start on day 43) of Nivolumab IV 240 mg q2 weekly for up to 1 year. |
Induction phase: Nivolumab IV 240 mg on days 1, 15 and 29 followed by a maintenance phase (to start on day 43) of Nivolumab IV 240 mg q2 weekly for up to 1 year.
All patients will receive standard fractionation radiation therapy (RT) scheme: 50Gy in 25 fractions over 5 weeks (i.e.
2Gy per fraction), concurrently with 3 cycles of 2 weeks of FOLFOX (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, bolus fluorouracil 400 mg/m2, and infusional fluorouracil 1600 mg/m2 over 48 h), followed by 3 cycles of 2 weeks of FOLFOX without RT.
|
Experimental: Arm B: Chemoradiation + Nivolumab + Ipilimumab
Same as arm A + induction phase: Ipilimumab IV 1 mg/kg on day 1 followed by a maintenance phase (to start on day 43) of Ipilimumab IV 1 mg/kg q6 weekly for up to 1 year
|
Induction phase: Nivolumab IV 240 mg on days 1, 15 and 29 followed by a maintenance phase (to start on day 43) of Nivolumab IV 240 mg q2 weekly for up to 1 year.
All patients will receive standard fractionation radiation therapy (RT) scheme: 50Gy in 25 fractions over 5 weeks (i.e.
2Gy per fraction), concurrently with 3 cycles of 2 weeks of FOLFOX (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, bolus fluorouracil 400 mg/m2, and infusional fluorouracil 1600 mg/m2 over 48 h), followed by 3 cycles of 2 weeks of FOLFOX without RT.
Induction phase: Ipilimumab IV 1 mg/kg on day 1 followed by a maintenance phase (to start on day 43) of Ipilimumab IV 1 mg/kg q6 weekly for up to 1 year.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
12-Month Progression-free survival using RECIST 1.1
Time Frame: 3.8 years from first patient in
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Best overall response according to RECIST 1.1
Time Frame: 3.8 years from first patient in
|
3.8 years from first patient in
|
|
Pattern of first cause of progression (either local relapse/progression,either regional relapse/progression, either distant metastasis)
Time Frame: 3.8 years from first patient in
|
3.8 years from first patient in
|
|
Progression-free survival using RECIST 1.1
Time Frame: 3.8 years from first patient in
|
3.8 years from first patient in
|
|
Failure-free survival
Time Frame: 3.8 years from first patient in
|
3.8 years from first patient in
|
|
Overall survival
Time Frame: 3.8 years from first patient in
|
3.8 years from first patient in
|
|
Percentage of patients receiving the planned chemoradiation
Time Frame: 3.8 years from first patient in
|
3.8 years from first patient in
|
|
Relative dose intensity of oxaliplatinum
Time Frame: 3.8 years from first patient in
|
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
|
Relative dose intensity of 5FU
Time Frame: 3.8 years from first patient in
|
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
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Head and Neck Neoplasms
- Esophageal Diseases
- Esophageal Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
- Ipilimumab
Other Study ID Numbers
- EORTC-1714
- 2018-000053-53 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Inoperable œsophageal Cancer
-
Novartis PharmaceuticalsTerminatedMetastatic Breast Cancer (MBC) | Inoperable Locally Advanced Breast CancerFrance, Spain
-
AstraZenecaRecruitingLocally Advanced (Inoperable) or Metastatic Breast CancerUnited States, Spain, Denmark, Korea, Republic of, Germany, Belgium, Vietnam, United Kingdom, France, Japan, Brazil, Canada, China, Malaysia, Taiwan, Thailand, Australia, Turkey, Argentina, India, Poland, Sweden, Italy
-
Yonsei UniversityCompleted
-
BeiGeneCompletedAdvanced or Inoperable Gastric CancerUnited States, Hungary, Spain, China, Hong Kong, Japan, Australia, Taiwan, Belgium, Czechia, Singapore, France, Poland, United Kingdom, Romania, Russian Federation, Georgia
-
Hoffmann-La RocheRecruitingInoperable, Locally Advanced or Metastatic, ER-positive Breast CancerUnited States, Korea, Republic of, Spain, Australia, Israel
-
AstraZenecaActive, not recruitingLocally Advanced (Inoperable) or Metastatic Breast CancerUnited States, Italy, Spain, Belgium, Hungary, Poland, Canada, France, Germany, Korea, Republic of, Japan, Peru, Russian Federation, United Kingdom, China, Taiwan, Israel, Australia, Argentina
-
University of Texas Southwestern Medical CenterCelgeneCompletedSTAGE IIIA/B NSCLC / INOPERABLE LUNG CANCERUnited States
-
AstraZenecaTerminatedInoperable Locally Advanced or Metastatic Biliary Tract CancerJapan
-
Eisai Co., Ltd.CompletedInoperable or Recurrent Breast CancerJapan
-
The First People's Hospital of LianyungangThe East Hospital of Lianyungang; Donghai People's Hospital; People's Hospital...UnknownInoperable Esophageal Cancer Stage I-IIIChina
Clinical Trials on Nivolumab
-
Universitair Ziekenhuis BrusselNot yet recruiting
-
Brown UniversityBristol-Myers Squibb; The Miriam Hospital; Rhode Island Hospital; Women and Infants...Terminated
-
Bristol-Myers SquibbRecruitingMelanomaSpain, United States, Italy, Chile, Greece, Argentina
-
Baptist Health South FloridaBristol-Myers Squibb; NovoCure Ltd.TerminatedRecurrent GlioblastomaUnited States
-
Jason J. Luke, MDArray BioPharmaActive, not recruitingMelanoma | Renal Cell Carcinoma | Solid Tumor | Non-small Cell Lung Cancer | Head and Neck Squamous Cell CarcinomaUnited States
-
HUYABIO International, LLC.Bristol-Myers SquibbRecruitingUnresectable or Metastatic Melanoma | Progressive Brain MetastasisSpain, United States, Italy, Japan, Belgium, France, New Zealand, Brazil, Korea, Republic of, Australia, Germany, Singapore, Czechia, Austria, South Africa, United Kingdom, Puerto Rico
-
Michael B. Atkins, MDBristol-Myers Squibb; Hoosier Cancer Research NetworkActive, not recruitingAdvanced Renal Cell CarcinomaUnited States
-
Bristol-Myers SquibbCompletedLung CancerItaly, United States, France, Russian Federation, Spain, Argentina, Belgium, Brazil, Canada, Chile, Czechia, Germany, Greece, Hungary, Mexico, Netherlands, Poland, Romania, Switzerland, Turkey, United Kingdom
-
IRCCS San RaffaeleBristol-Myers SquibbRecruiting
-
National Health Research Institutes, TaiwanNational Taiwan University Hospital; Mackay Memorial Hospital; China Medical... and other collaboratorsRecruitingHepatocellular Carcinoma (HCC)Taiwan