Safety and Feasibility of Irradiation and Nivolumab in Esophageal Cancer (INEC)

NCT03544736 | Active Not Recruiting Phase 1

• 1 other identifier: CA209-9M9-03
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Three parallel cohort, multicenter, open-label, phase I/II clinical trial to analyze the safety and feasibility of PD-1 inhibition with Nivolumab given concomitantly with standard radiotherapy regimens in the treatment of esophageal cancer

Conditions

Esophageal Cancer

Keywords

Nivolumab; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Safety and Tolerability; Incidence of adverse events using CTCAE 5.0

  From date of treatment allocation until first date of documented disease progression or death assessed during study period or up to at least 100 days after last dose

Secondary Outcomes (6)

• Response to treatment

  From date of treatment allocation and during treatment period up to 2 years

• Overall Survival

  From date of treatment allocation until first date of documented death assessed up to 5 years after completed treatment

• Progression Free Survival

  From date of treatment allocation until first date of documented disease progression or death assessed up to 5 years after completed treatment

• Health Related Quality of Life (EQ-5D)

  From date of treatment allocation until first date of documented disease progression or death assessed up to 5 years after completed treatment

• Health Related Quality of Life (EORTC QLQ-C30)

  From date of treatment allocation until first date of documented disease progression or death assessed up to 5 years after completed treatment

Study Arms (3)

Cohort A

EXPERIMENTAL

Subjects having palliative radiotherapy towards esophageal tumor will receive concomitant therapy With Nivolumab i.v. 240mg Q2W: first 6 patients, 360mg Q3W: Next 6 patients or 480mg Q4W: Last 6 patients, treatment to progression or up to 2 years of treatment. Radiotherapy: 2 Gy / day, (5 fx/week) to a total of 20 - 50 Gy in 25fx (2-4Gy/fx) at the decision of the responsible physician.

Drug: Nivolumab; Radiation: Radiotherapy

Cohort B

EXPERIMENTAL

Subjects receiving definitive chemoradiotherapy for esophageal cancer will receive concomitant therapy with Nivolumab 240mg Q2W, during RT, and continued with 480mg Q4W, treatment to progression or up to 1 year after completion of radiotherapy. 6 patients in total. Chemotherapy: Paclitaxel i.v. 175mg/m2 and Carboplatin AUC5, then after 21 days Radiotherapy 1,8 Gy / day (5 fx/week) up to 50,4 Gy in 28fx and concomitantly Paclitaxel 50mg/m2 and Carboplatin AUC2 Q1W and Nivolumab as described above.

Drug: Nivolumab; Radiation: Radiotherapy; Drug: Chemotherapy

Cohort C

EXPERIMENTAL

Subjects with operable esophageal cancer eligible for neoadjuvant chemoradiotherapy will receive Nivolumab 240mg Q2W, concomitantly with RT Then surgery 4-12 weeks after RT. Within 6-12 months after surgery: Adjuvant Nivolumab 480mg Q4W, for 12 months. 6 patients in total. Neoadjuvant chemotherapy: Concomitantly Paclitaxel 50mg/m2 and Carboplatin AUC2 Q1W and Radiotherapy: 41,4 Gy in 23 fractions.

Drug: Nivolumab; Radiation: Radiotherapy; Drug: Chemotherapy; Procedure: Surgery

Interventions

Nivolumab DRUG

Experimental: Nivolumab

Also known as: Opdivo

Cohort A; Cohort B; Cohort C

Radiotherapy RADIATION

Radiotherapy

Cohort A; Cohort B; Cohort C

Chemotherapy DRUG

Chemotherapy

Also known as: Paclitaxel and Carboplatin

Cohort B; Cohort C

Surgery PROCEDURE

Surgery

Cohort C

Eligibility Criteria

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

You may qualify if:

• Three different cohorts of patients with esophageal cancer are studied.
• All of the following conditions must apply to the prospective patient at screening prior to receiving study treatment or any study related procedures (e.g.):
• Age \> 18 years
• Patients should have previously untreated histologically proven squamous cell carcinoma or adenocarcinoma of the esophagus or the gastroesophageal junction (GEJ), Siewert I, II or III
• Must be ambulatory with a performance status ECOG 0 or 1
• Adequate organ function based on clinical examination and lab values as defined in the below:
• Absolute neutrophil count: ≥ 1,5 x109/L Platelets: ≥ 100 x109/L Hemoglobin: ≥ 9 x109/L Creatinine ≤ 1,5 upper limit normal (ULN) OR measured/calculated GFR≥60 mL/min Albumin ≥ 30 g/L Total bilirubin ≤ 1,5 ULN ASAT and ALAT ≤ 2,5 ULN, or ≤ 5 ULN for subjects with liver mets. International Normalized Ratio (INR) ≤ 1,5 ULN and Activated Partial Thromboplastin Time (TT) ≤ 1,5 ULN unless subject is receiving anticoagulant therapy. Such therapy (if indicated) should be converted to adequate therapy with low-molecular weight heparin such as Dalteparin before chemotherapy or treatment with IMP.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 28 days prior to the start of study drug (screening phase). Women must not be breastfeeding.
• WOCBP should use highly effective adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for Nivolumab to undergo five half-lives) after the last dose of investigational drug. Adequate methods are described in Appendix I.
• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception during the study treatment period and until 7 months after last dose of Nivolumab (see Appendix I).
• Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.
• If Dysphagia score \>2, a nasogastric feeding tube should be inserted during the aid of gastroscopy, and nasogastric tube feeding started before radiotherapy.
• In addition, specific criteria are defined for the three different patient cohorts below:
• Eligible for palliative fractionated radiotherapy of the esophageal- or gastroesophageal cancer as determined by the multidisciplinary team (MDT) meeting.
• Expected survival \>3 months

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria:
• Previous treatment with radiotherapy towards volumes within the thoracic cavity
• Previous treatment with any PD-1 or PD-L1/2 inhibitor
• Hypersensitivity to the investigational product or any of the drug formula contents
• Esophageal stenting
• T4b if infiltration into the aorta or the trachea
• History of prior autoimmune disorders requiring systemic therapy (excluding Insulin or Thyroid replacement therapy)
• History of HIV 1 /2, Hepatitis B or C infection
• History of Immunodeficiency disorders (i.e. immunoglobulin deficiency or white blood cell lineage depletion disorders)
• Participation in any other interventional clinical trial with an investigational product
• History of prior malignancy within the last 5 years, excluding curatively treated basal cell or squamous cell carcinoma of the skin.
• Known history of brain metastases
• Need to use immunosuppressive drugs including, but not limited to: Glucocorticoids, everolimus, sirolimus, disease-modifying anti-rheumatic drugs (DMARDS)
• Positive pregnancy test (positive hCG blood test)
• Known allergy, hypersensitivity, or contraindication to the investigational product Nivolumab, or the drugs paclitaxel and docetaxel used in the standard chemoradiotherapy protocols (Cohorts B and C) or any components used in their preparation or has a contraindication to taxane therapy.

Sponsors & Collaborators

• Oslo University Hospital: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Oslo University Hospital

Oslo, 0424, Norway

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Nivolumab; Radiotherapy; Drug Therapy; Paclitaxel; Carboplatin; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Geir O. Hjortland

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Open-label, non-randomized, Parallell Groups, Study of Nivolumab and Radiotherapy in Patients With Esophageal Cancer

Study Record Dates

• First Submitted: April 25, 2018
• First Posted: June 4, 2018
• Study Start: April 26, 2018
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2040
• Last Updated: March 22, 2023

Record last verified: 2023-03

Locations

NO (1)