Overview

Durvalumab as Maintenance Following Chemoradiation for Unresectable Esophageal Squamous Cell Carcinoma

Status:
Not yet recruiting

Trial end date:
2022-10-01

Target enrollment:
0

Participant gender:
All

Summary

Single arm phase II trial designed to assess the efficacy of durvalumab treatment in terms of 6-month progression-free survival. We will include 22 patients who will receive 1500 mg durvalumab (MEDI4736) via IV infusion Q4W <> or <> unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. If a patient's weight falls to 30 kg or below for 1 week or longer ( ≥ 7 days) durvalumab will be permanently discontinued.

Phase:

Phase 2

Accepts Healthy Volunteers?

Details

Lead Sponsor:

Tiago Biachi

Treatments:

Antibodies, Monoclonal
Durvalumab

Criteria

Inclusion Criteria:

1. Body weight >30kg and body mass index ≥ 16 kg / m2;

2. Patients aphagic or able to ingest only liquids should also receive enteral
nutritional sup-port before being included in the study;

3. Patients must have histologically confirmed esophageal or esophagogastric junction
(Siewert I or II) squamous cell carcinoma, irrespective of PD-1/PD-L1 or other
biomarkers expression;

4. Patients must have had a persistent disease 6-8 weeks after completing
chemoradiotherapy with at least 50 Gy and platinum-based chemo and without complete
response or progressive disease, based on upper endoscopy and/or CT scans;

5. Patients must have realized CT scans within 6-8 weeks after completion of
chemoradiotherapy, revealing persistent disease;

6. Patients must be included <12 weeks after completing chemoradiotherapy;

7. Patients must be unsuitable to salvage esophagectomy, according multidisciplinary
local board;

8. All the tumor volume should have been treated with CRT (included in the radiation
field);

9. Eastern Cooperative Oncology Group (ECOG)>>< performance status of 0 or 1;

10. Male or female aged 18 years or older at time of study entry;

11. Life expectancy of > 12 weeks;

12. Adequate normal organ and marrow function as defined below:

- Haemoglobin ≥9.0 g/dL

- Absolute neutrophil count (ANC) 1.5 x (> 1500 per mm3)

- Platelet count ≥100 x 109/L

- Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). < apply to patients with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis
or hepatic pathology), who will be allowed only in consultation with their
physician.

- AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver
metastases are present, in which case it must be ≤5x ULN

- Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40
mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour
urine collection for determination of creatinine clearance: CrCl, mL/min = (140 -
age) × (weight, kg) × (0.85 if female) / (72 × Cr)

13. All toxicities attributed to prior chemoradiotherapy other than alopecia, fatigue, or
peripheral neuropathy must have resolved to grade 2 or less;

Exclusion Criteria:

1. Patients with metastases including lymph node not included in the radiation field;

2. Patients currently receiving or have had prior use of immunosuppressive medication
within 28 days before the first dose of study drug (10 milligrams/day of prednisone or
an equivalent corticosteroid is allowed);

3. Received any immunotherapy for esophageal cancer;

4. Patients with active hepatitis B, hepatitis C or human immunodeficiency virus (HIV1/2
antibodies);

5. Has known active or prior autoimmune disease, except for:

- skin diseases (vitiligo, psoriasis, alopecia)

- diabetes mellitus type 1, with hormone replacement

- hypothyroidism, with hormone replacement

6. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.

7. Grade 3 or higher pulmonary toxicity of dyspnea, hypoxia, or pneumonitis experienced
during chemoradiation;

8. Presence of fistula between esophagus and trachea unless treated with endoscopic
prosthesis.