Safety and Feasibility of Irradiation and Nivolumab in Esophageal Cancer (Inec-Study) – a Phase I/Ii Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

28 Sep 2024 → ongoing

Decision date (initial)

2024-09-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-510124-77-01

EudraCT number

2017-003132-36

ClinicalTrials.gov

NCT03544736

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

Safety measurements done to determine the safety profile of the treatment; safety parameters included adverse events, biochemistry, hematology, vital signs and performance status.
Adverse events are recorded according to CTCAE v5.0 (CTCAE grade 2-5 rate)

Secondary objectives 5

1. Response to treatment: Cohort A: Out- and Infield Overall Response Rate (RECIST v1.1), Overall Survival.
2. Response to treatment: Cohort B: Progression free survival, Overall Survival
3. Response to treatment: Cohort C: Pathologic complete response rate at surgery (pCR) , Clavien Dindo, Recurrence free survival, Overall Survival
4. Quality of life (QLQ-C30, QLQ-OG2 and EQ-5D)
5. Exploratory & translational end points

Conditions and MedDRA coding

Eosophageal cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Age > 18 years
2. 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
3. Must be ambulatory with a performance status ECOG 0 or 1
4. Adequate organ function based on clinical examiniation 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/calculaterd 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.
5. 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.
6. 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.
7. 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
8. 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.
9. If Dysphagia score >2, a nasogastric feeding tube should be inserted during the aid of gastroscopy, and nasogastric tube feeding started before radiotherapy.
10. Specific inclusion criteria - Cohort A: 1. Eligible for palliative fractionated radiotherapy of the esophageal- or gastroesophageal cancer as determined by the multidisciplinary team (MDT) meeting. 2. Expected survival >3 months. 3. Not bulky disease, i.e. palliative radiotherapy towards the primary tumor is intended to palliate dysphagia and/or pain and systemic treatment could be delayed to AFTER protocol therapy if possible.
11. Specific inclusion criteria – Cohort B: 1. Eligible for definitive chemoradiation of localized but inoperable esophageal- or gastroesophageal cancer as determined by the multidisciplinary team (MDT) meeting. 2. Regional disease, i.e. no metastasis outside the radiation field (PTV). 3. Considered candidate/ able to adhere to the intended chemoradiotherapy
12. Specific inclusion criteria – Cohort C: 1. Eligible for neoadjuvant chemoradiotherapy and surgery of the esophageal- or gastroesophageal cancer as determined by the multidisciplinary team (MDT) meeting. 2. Regional disease, i.e. no metastasis outside the radiation field (PTV). 3. Considered candidate and able to adhere to the intended neoadjuvant chemoradiotherapy and planned surgery.

Exclusion criteria 15

1. Previous treatment with radiotherapy towards volumes within the thoracic cavity
2. Previous treatment with any PD-1 or PD-L1/2 inhibitor
3. Hypersensitivity to the investigational product or any of the drug formula contents
4. Esophageal stenting
5. T4b if infiltration into the aorta or the trachea
6. History of prior autoimmune disorders requiring systemic therapy (excluding Insulin or Thyroid replacement therapy)
7. History of HIV 1 /2, Hepatitis B or C infection
8. History of Immunodeficiency disorders (i.e. immunoglobulin deficiency or white blood cell lineage depletion disorders)
9. Participation in any other interventional clinical trial with an investigational product
10. History of prior malignancy within the last 5 years, excluding curatively treated basal cell or squamous cell carcinoma of the skin.
11. Known history of brain metastases
12. Need to use immunosuppressive drugs including, but not limited to: Glukocorticoids, everolimus, sirolimus, disease-modifying anti-rheumatic drugs (DMARDS)
13. Positive pregnancy test (positive hCG blood test)
14. 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.
15. Any reason why, in the opinion of the investigator, the patient should not participate.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety: The primary end point in this study is safety measurements done to determine the safety profile of the treatment; safety parameters included adverse events, biochemistry, hematology, vital signs and performance status. Adverse events are recorded according to CTCAE v5.0 (CTCAE grade 2-5 rate).
2. Feasibility: The feasibility of conducting the study will be reported as number of patients screened, and number of patients successfully included into the study per one year of accrual time.

Secondary endpoints 6

1. Overall Survival: The time from onset of treatment (day 1) to death from any cause.
2. Infield and Outfield Response to Treatment: The response rate as measured by RECIST 1.1 and immune-related RECIST (ir-RECIST) within the irradiated volume (infield) verses outside the irradiated volume (outfield).
3. Progression Free Survival (Only Cohort B): The time from treatment start (day -21) until the disease progresses (PD) as determined by investigators from tumor assessments per RECIST or death from any cause.
4. Disease Free Survival (Only Cohort C): The time from surgery until recurrency or occurrence of disease progression as determined by investigators from tumor assessments per RECIST.
5. Pathology Complete Response Rate (Only Cohort C): The complete response rate in the surgical specimen by Chirieac grading by pathologist.
6. Quality of Life:Quality of Life Questionnaires (QLQ) by patient reported outcomes EORTC QLQ-C30, EORTC QLQ-OG25 and EQ-5D.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

Geir Olav Hjortland

Public contact point

Organisation

Oslo University Hospital HF

Contact name

Geir Olav Hjortland

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications