Assessment of Metabolic & Path Response w/ RCT & ImT Before Surgery in Locally Advanced Esoph and Gastro-esoph Jction CA

NCT03307941 | Withdrawn Phase 1

• 2 other identifiers: IJB-GASTON-002-ARTEMIS-Eso2016-000935-42
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

ARTemIS-Eso is a phase I-II, three-level, open-label trial with a dose-expansion cohort at recommended schedule in both esophageal cancer histological groups (squamous cell carcinoma and adenocarcinoma) of RCT and ImT administered prior to surgery.

Conditions

Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Squamous Cell Carcinoma of the Esophagus

Outcome Measures

Primary Outcomes (2)

• Phase I: determine the feasibility to administer monalizumab

  Successful and safe administration of the combination of radio-chemotherapy and at least 2 doses of immunotherapy

  From date of randomization until the date of first documented disease recurrence, assessed up to 28 months

• Phase II: pCR rate

  Defined by the absence of any tumoral cells on the surgical specimen post esophagectomy

  At date of surgery, assessed at 16 weeks post randomization

Secondary Outcomes (7)

• Phase I: pCR rate

  At date of surgery, assessed at 16 weeks post randomization

• Phase I: DFS and OS at 2 years after surgery

  From date of randomization until the date of first documented event, assessed up to 28 months

• Phase I: Human Anti-Human Antibodies against monalizumab (HAHA) in serum

  Week 5 to 3 months post surgery

• Phase II: Two year-disease free survival (DFS) and two year-overall survival (OS)

  2 years after the date the last patient had his surgery provided the trial objectives have been met

• Phase II: Toxicity profile according to CTCAE v.4.03

  From date of randomization until the date of first documented event, assessed up to 28 months

Study Arms (1)

Single arm (classic 3+3 design)

OTHER

Drug: Monalizumab; Drug: Oxaliplatin; Drug: 5-Fluorouracil; Radiation: Metabolic; Other: Metabolic; Procedure: Surgery

Interventions

Monalizumab DRUG

Monalizumab (IPH2201) is given at the recommended dose of 10 mg/kg, intravenously (infusion during 60 minutes) every two weeks

Also known as: IPH2201

Single arm (classic 3+3 design)

Oxaliplatin DRUG

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

Single arm (classic 3+3 design)

5-Fluorouracil DRUG

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

Single arm (classic 3+3 design)

Metabolic RADIATION

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.

Single arm (classic 3+3 design)

Surgery PROCEDURE

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

Single arm (classic 3+3 design)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old
• ECOG performance status ≤ 1
• Female and Male
• 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.
• At least classified clinical T3Nx or any T, N+ according to cTNM version 7.
• Negative serum pregnancy test (for women of childbearing potential) within 7 (+/-1) days prior to the beginning of treatment.
• 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.
• 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.
• 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
• 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

You may not qualify if:

• Subjects meeting one of the following criteria are not eligible for this study:
• 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
• Uncontrolled concurrent illness or any significant disease that, in the investigator's opinion, would exclude the patient from the study.
• 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.
• Pregnant and/or lactating women.
• Uncontrolled diabetes.
• 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.
• 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.

Sponsors & Collaborators

• Jules Bordet Institute: lead
• Innate Pharma: collaborator

Study Sites (1)

Institut Jules Bordet

Brussels, 1000, Belgium

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Squamous Cell Carcinoma

Interventions

monalizumab; Oxaliplatin; Fluorouracil; Metabolic Networks and Pathways; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Metabolism

Study Officials

• Amelie Deleporte, Physician

  Jules Bordet Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2016
• First Posted: October 12, 2017
• Study Start: July 20, 2017
• Primary Completion: December 11, 2017
• Study Completion: December 11, 2017
• Last Updated: December 19, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)