Association of Radiochemotherapy and Immunotherapy for the Treatment of Unresectable Oesophageal caNcer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 May 2019 → ongoing

Decision date (initial)

2024-05-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca

External identifiers

EU CT number

2024-512165-13-00

EudraCT number

2018-000708-40

ClinicalTrials.gov

NCT03777813

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective is to assess the efficacy of durvalumab, initially in combination with (FOLFOX and IMRT 50 Gy) and then as maintenance therapy for treating patients with localized unresectable oesophageal cancer, in terms of PFS (centrally reviewed; cPFS)

Secondary objectives 4

1. To assess the efficacy in terms of local PFS.
2. To assess the efficacy in terms of overall survival.
3. To evaluate the safety and tolerance of the study treatments.
4. To evaluate the quality of life.

Conditions and MedDRA coding

Localised unresectable adenocarcinoma or squamous cell carcinoma of the oesophagus without any prior chemotherapy, surgery, or radiotherapy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Histologically proven squamous cell carcinoma or adenocarcinoma of the oesophagus,
2. Unresectable disease due to anatomical consideration or medical condition, (patient unfit for surgical procedure),
3. Presence of at least one measurable lesion >10 mm with spiral CT scan,
4. No prior therapy for pathology investigated including chemotherapy or radiotherapy prior to the study, except anterior out of field radiotherapy, received for treatment of another primary tumor considered in remission in the past 5 years,
5. Age ≥18 years old,
6. WHO performance status <2 (i.e., 0 or 1),
7. Body weight >35 kg,
8. Life expectancy of at least 12 weeks ,
9. Adequate haematology laboratory data within the 7 days before randomization
10. Adequate Biochemistry laboratory data within the 7 days before randomization
11. Adequate haemostasis laboratory data within 7 days prior to randomization: prothrombin time (PT) within the normal range,
12. Adequate values for calcium, potassium and magnesium levels measured within 7 days prior to randomization
13. Women should be post-menopaused or willing to accept the use an effective contraceptive regimen during the treatment period and for at least 6 months after the end of the study. All non-menopausal women should have a negative pregnancy test within 72 h prior to randomization. Men should accept to use an effective contraception during treatment period and at least 6 months after the end of the study especially after the last dose of oxaliplatin treatment.
14. Patients must have provided consent for the study by signing and dating a written informed consent form prior to any study specific procedures, sampling, or analyses,
15. Patient affiliated to a social security regimen.
16. Uracilemia < 16ng/ml
17. Forced expiratory volume (FEV) >1 liter or > 50% of the theoretical value

Exclusion criteria 27

1. Previous treatment with another PD-1, PD-L1 including durvalumab or CTLA-4 inhibitor
2. Metastatic disease,
3. Patients should not receive live vaccine 30 days prior to study drug
4. Female patients who are pregnant or breastfeeding
5. Uncontrolled intercurrent illness including, but not limited to diabetes, hypertension, pulmonary failure, chronic renal or hepatic diseases, active peptic ulcer disease or gastritis, active bleeding, diatheses... (non-exhaustive list),
6. Clinically significant cardiac disease or impaired cardiac function,
7. Current or prior use of immunosuppressive medication within 28 days before the first administration of durvalumab (exception: systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or equivalent are allowed as well as steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) - Topical, inhaled, nasal, and ophthalmic steroids are allowed,
8. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]).
9. Known primary immunodeficiency or active HIV,
10. Patient with a dihydropyrimidine dehydrogenase (DPD) deficiency (Uracilemia ≥ 16 ng/ml, the test should be done for all patients before 5-FU administration)* ,
11. Known active or chronic viral hepatitis or history of any type of hepatitis within the last 6 months indicated by positive HBS antibody test for hepatitis B or hepatitis C virus ribonucleic acid (HCV antibody),
12. History of organ transplantation requiring the use of immunosuppressive medication, including allogenic stem cell transplant
13. History of active tuberculosis or latent disease capable of reactivation,
14. Current pneumonitis or interstitial lung disease,
15. Other invasive malignancy within 2 years prior to entry into the study, except for those treated with surgical therapy only,
16. History of severe allergic reactions or hypersensitivity to any unknown allergens or any components of the study drug (refer to IB of durvalumab section 5.5.1.11).
17. Any prior corticosteroid-refractory immune-related adverse event (irAE),
18. Oeso-tracheal or oeso-bronchial fistulae,
19. Major surgery within 28 days prior to the first dose of study treatment
20. Toxicities of grade ≥1 from any previous therapy
21. Peripheral sensory neuropathy with functional impairment
22. Severe infection requiring parenteral antibiotic treatment
23. Patients treated with sorivudine or analogues as brivudine
24. Patients treated with phenytoin for prophylaxis
25. Participation in another therapeutic trial within the 30 days prior to study inclusion,
26. Patients deprived of liberty or under guardianship,
27. Patients unable to adhere to the protocol for geographical, social, or psychological reasons.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is defined by a blinded independent centralized revue of progression free survival. cPFS is defined as the time from randomization until progression or death; patients alive and without documented progression at last follow-up news have PFS censored at this date or at initiation of new anticancer treatment (if applicable). Progression will be assessed by a blinded independent centralized revue of TDM per RECIST criteria 1.1

Secondary endpoints 4

1. Progression-Free Survival (PFS) is defined as the time from randomization until progression or deaths; patients alive and without progression at last follow-up news are censored at this date.
2. Overall survival (OS): OS is defined by the delay between randomization and the occurrence of death due to any cause. Patients still alive at the time of analysis (including lost of follow-up) will be censored at the last known alive date.
3. Safety: safety will be assessed by the toxicity grading of the National Cancer Institute (NCI-CTCAE v 5.0, appendix 3). Adverse event (AE) occurrence will be detected by changes occurring in the course of treatment observed during clinical examination, in particular on vital signs (artery pressure, pulse, body temperature), in electrocardiogram (ECG) and biological tests (biochemistry, hematology). Use of concomitant treatments will be also taken into account.
4. Quality of life: Quality of life (QL) assessed by the European Organization for Research and Treatment of Cancer (EORTC) core QL questionnaire, the EORTC QLQ-C30 and Oes18 (Oesophageal Cancer Module).

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 23 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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