Inoperable œsophageal CancerPhase 2CRUCIALNCT03437200
Combination of Chemoradiation With Immunotherapy in Inoperable œsophageal Cancer
A Phase 2 study testing Nivolumab, Ipilimumab and Chemoradiation in people with Inoperable œsophageal Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 7 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Inoperable œsophageal Cancer
- What is being tested?
- Nivolumab, Ipilimumab and Chemoradiation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 17 Jan 2019to 7 Oct 2022
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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.
Show all 20Show fewer
- 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.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
Spain5 sites
Hospital Del Mar
Barcelona, 08003
Institut Catala d'Oncologia - ICO Badalona - Hospital De Mataro
Barcelona, 08304
Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)
Barcelona, 08908
Hospital Universitario de Gran Canaria Doctor Negrin
Las Palmas de Gran Canaria, 35019
Hospital Universitario 12 De Octubre
Madrid, 28041
France2 sites
Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere
Paris, 75651
Institut Gustave Roussy
Villejuif, 94805
About this study
Official title: 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).
- Conditions
- Inoperable œsophageal Cancer
- Being tested
- Nivolumab, Ipilimumab, Chemoradiation
- Keywords
- œsophageal cancer nivolumab ipilimumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
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.
IpilimumabDrug
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.
ChemoradiationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Chemoradiation + Nivolumab | Experimental | 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. Receives: Drug: Nivolumab; Other: Chemoradiation |
| Arm B: Chemoradiation + Nivolumab + Ipilimumab | Experimental | 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 Receives: Drug: Nivolumab; Drug: Ipilimumab; Other: Chemoradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 3.8 years from first patient in
Secondary outcomes (8)
Best overall response according to RECIST 1.1
Measured: 3.8 years from first patient in
Pattern of first cause of progression (either local relapse/progression,either regional relapse/progression, either distant metastasis)
Measured: 3.8 years from first patient in
Progression-free survival using RECIST 1.1
Measured: 3.8 years from first patient in
Failure-free survival
Measured: 3.8 years from first patient in
Overall survival
Measured: 3.8 years from first patient in
Percentage of patients receiving the planned chemoradiation
Measured: 3.8 years from first patient in
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.
Measured: 3.8 years from first patient in
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.
Measured: 3.8 years from first patient in
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study start17 Jan 2019
- Primary completion7 Oct 2022
- Study completion7 Oct 2022
Why it stopped: Poor accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inoperable œsophageal CancerStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Eric Deutsch, Principal investigator, INSTITUT GUSTAVE ROUSSY, Paris, FranceMarkus Moehler, Principal investigator, UNIVERSITY MEDICAL CENTER MAINZ, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03437200
- Sponsor's protocol ID
- EORTC-1714
- Other IDs
- 2018-000053-53, 2018
- Acronym
- CRUCIAL
- Status last verified
- Feb 2023
- First submitted
- 6 Feb 2018
- Last updated
- 21 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No