Assessment of Metabolic & Path Response w/ RCT & ImT Before Surgery in Locally Advanced Esoph and Gastro-esoph Jction CA
NCT ID: NCT03307941
Last Updated: 2017-12-19
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
WITHDRAWN
PHASE1/PHASE2
INTERVENTIONAL
2017-07-20
2017-12-11
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
The study consists of 2 parts:
Phase I of the study is composed of the 3 following levels, corresponding to changes in the schedule and the number of administrations of monalizumab:
Level 1: monalizumab (ImT) administration starts 2 weeks after the end of RCT (Total of 3 ImT doses). A maximum of 7 days delay is allowed.
Level 2: monalizumab administration starts directly at the end of RCT (Total of 4 ImT doses). The first dose of monalizumab should be given on the following working day after the last radiotherapy administration.
Level 3: monalizumab administration starts 2 weeks after the start of RCT (total of 6 ImT doses). A maximum of 7 days delay is allowed.
Phase II (Expansion cohort): At the recommended level determined in phase I and according to the number of patients already accrued, approximately 48-51 additional patients (half-SCC and half-ADC) are included with the aim of assessing the activity of the recommended combination.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Single arm (classic 3+3 design)
Monalizumab
Monalizumab (IPH2201) is given at the recommended dose of 10 mg/kg, intravenously (infusion during 60 minutes) every two weeks
Oxaliplatin
A total of 4 cycles of FOLFOX is administrated every 2 weeks with one cycle 15 days prior to the radiotherapy and 3 cycles during the radiotherapy whatever the level
5-Fluorouracil
A total of 4 cycles of FOLFOX is administrated every 2 weeks with one cycle 15 days prior to the radiotherapy and 3 cycles during the radiotherapy whatever the level
Metabolic
Radiation therapy must start the first day of FOLFOX chemotherapy. Radiation is given once daily for 5 consecutive days; on the days that the patient receives chemotherapy (and monalizumab when applicable), chemotherapy (and monalizumab) should be given prior to radiotherapy.
Metabolic
18-FDG-PET scan will be performed just before the beginning of radio-chemotherapy (D10-D14) and will be blinded for investigators and patients. Another 18-FDG-PET will be performed before surgery (surgery Day-5 to surgery Day -1) to exclude metastatic evolution
Surgery
Surgery is performed preferably 8 weeks after the completion of the radio-chemotherapy, and it should not be performed less than one week after the last dose of monalizumab
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Monalizumab
Monalizumab (IPH2201) is given at the recommended dose of 10 mg/kg, intravenously (infusion during 60 minutes) every two weeks
Oxaliplatin
A total of 4 cycles of FOLFOX is administrated every 2 weeks with one cycle 15 days prior to the radiotherapy and 3 cycles during the radiotherapy whatever the level
5-Fluorouracil
A total of 4 cycles of FOLFOX is administrated every 2 weeks with one cycle 15 days prior to the radiotherapy and 3 cycles during the radiotherapy whatever the level
Metabolic
Radiation therapy must start the first day of FOLFOX chemotherapy. Radiation is given once daily for 5 consecutive days; on the days that the patient receives chemotherapy (and monalizumab when applicable), chemotherapy (and monalizumab) should be given prior to radiotherapy.
Metabolic
18-FDG-PET scan will be performed just before the beginning of radio-chemotherapy (D10-D14) and will be blinded for investigators and patients. Another 18-FDG-PET will be performed before surgery (surgery Day-5 to surgery Day -1) to exclude metastatic evolution
Surgery
Surgery is performed preferably 8 weeks after the completion of the radio-chemotherapy, and it should not be performed less than one week after the last dose of monalizumab
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. ECOG performance status ≤ 1
3. Female and Male
4. Must have histologically confirmed esophageal ADC or SCC or gastro-esophageal junction ADC (Siewert I and II) eligible for a curative intent resection (recommended exploration by EUS and diagnostic laparoscopy in gastro-esophageal junctions) without restriction in age and sex and candidate for neoadjuvant RCT.
5. At least classified clinical T3Nx or any T, N+ according to cTNM version 7.
6. Negative serum pregnancy test (for women of childbearing potential) within 7 (+/-1) days prior to the beginning of treatment.
7. Women of childbearing potential must agree to use one highly effective method of contraception at study entry (if this is not already the case, put in place within 1 week after ICF signature, and at the very latest before 1st administration of study treatment), during the study treatment administration and at least 5 months after the last administration of study treatment.
8. Men must agree to use condom during the course of this study and for at least 5 months after the last administration of the study treatment.
9. Adequate bone marrow function as defined below:
* Absolute neutrophil count ≥1500/µL or 1.5x109/L
* Hemoglobin ≥ 9 g/dL
* Platelets ≥100000/µL or 100x109/L
10. Adequate liver function as defined below:
* Serum total bilirubin ≤ 1.5 x ULN. In case of known Gilbert's syndrome \< 3xUNL is allowed
* AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN
* Alkaline phosphatase ≤ 2.5 x ULN
11. Adequate renal function as defined:
* Creatinine ≤ 1.5 x UNL or creatinine clearance \>60 mL/min
12. Participants must have normal cardiac and pulmonary functions defined with ultrasonography (LVEF\>50%) and pulmonary function tests (including DLCO (diffusing capacity factor of the lung for carbon monoxide)).
13. Completion of all necessary screening procedures within 28 days prior to enrolment.
14. Accessible tumour for biopsies through upper gastro-intestinal endoscopy (for translational research activities).
15. Signed Informed Consent form (ICF) obtained prior to any study related procedure and study treatment.
16. For the phase II expansion cohort only, significant FDG uptake at the primary tumour on baseline PET/CT, performed not more than 7 days before the beginning of the first course of CT, defined as SUVmax \> 2x the mean liver uptake.
Exclusion Criteria
1. Patient ineligible for curative intent surgery:
* T4 with involvement of mediastinal structures as tracheobronchial, recurrent nerve, aorta over 90° of its circumference, vertebral body
* Tumour ≥ 4cm in diameter developed above the carina
* Visceral metastasis
* Metastatic lymph nodes: supraclavicular and/or lombo-aortic
* Cervical esophageal cancer defined as a tumor involving the lower border of the cricoid cartilage (at the level of the sixth cervical vertebra) to the thoracic inlet 5cm down under, generally between 18 and 20 cm from the dental arcade
2. Uncontrolled concurrent illness or any significant disease that, in the investigator's opinion, would exclude the patient from the study.
3. Absolute contraindication for surgery: respiratory failure (VEMS \< 1000mL), weight loss\> 20%, renal failure: creatinine \> 1.5 ULN, myocardial infarct \< 6 months, evolutive cardiopathy, ECOG 3 and 4, non-compensated cirrhosis.
4. Pregnant and/or lactating women.
5. Uncontrolled diabetes.
6. Individuals with a history of a different malignancy within the last 5 years are ineligible except cervical cancer in situ, and early stage basal cell or squamous cell carcinoma of the skin.
7. Patients with active, known or suspected autoimmune disease or condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive systemic treatment.
* (Exception: patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring immunosuppressive systemic treatment, or conditions not expected to recur in the absence of an external trigger, are permitted to be enrolled.
* Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active/autoimmune disease.
8. Patients with diseases known for hypersensitivity to radiotherapy.
9. Prior treatment for esophageal cancer: surgery, radiotherapy, chemotherapy or immunotherapy (in particular but not limited to anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumour vaccines or other immuno-stimulatory anti-tumour agents.
10. Positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (ribonucleic acid or HCV antibody) indicating acute or chronic infection.
11. Positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
12. History of allergy to study drug components or excipients.
13. Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Innate Pharma
INDUSTRY
Jules Bordet Institute
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Amelie Deleporte, Physician
Role: STUDY_CHAIR
Jules Bordet Institute
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Institut Jules Bordet
Brussels, , Belgium
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2016-000935-42
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
IJB-GASTON-002-ARTEMIS-Eso
Identifier Type: -
Identifier Source: org_study_id