Overview

Denosumab In Ebv Nasopharyngeal Carcinoma As A Model For RankMediated Immunologic Modulation Of Virus-Related Tumours

Status:
Recruiting
Trial end date:
2022-10-30
Target enrollment:
0
Participant gender:
All
Summary
The aim of the present investigation is to test of the modulation obtained with denosumab as "priming" therapy before the start of chemotherapy and as concurrent therapy in a population of first line NPC recurrent/metastatic patients
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Gruppo Oncologico del Nord-Ovest
Collaborator:
Mario Negri Institute for Pharmacological Research
Treatments:
Denosumab
Gemcitabine
Criteria
Inclusion Criteria:

1. EBV related nasopharyngeal cancer

2. Detectable and quantifiable plasmatic EBV DNA

3. Recurrent and/or metastatic disease not suitable for curative treatment

4. PS < 2

5. Suitable for polychemotherapy

6. Age ≥ 18 years

7. Informed consent signed

8. Subject has adequate organ functions, evidenced by the following:

1. AST (SGOT), ALT (SGPT) ≤ 2.5 x upper limit of normal range (ULN), or ≤ 5 x ULN
range if liver metastasis present

2. Total bilirubin ≤ 1.5 x ULN

3. creatinine clearance 24/h > 50 mL/min

4. Total serum calcium > 8.8 mg/dL

5. Absolute neutrophil count ≥ 1.5 x 10*9 cells/L

6. Platelets ≥ 100 x 10*9 cells/L

7. Haemoglobin ≥ 9 g/dL

9. If of childbearing potential, willingness to use effective contraceptive method (Pearl
Index < 1; e.g. oral contraceptive (pill), hormone spiral, hormone implant,
transdermal patch, a combination of two barrier methods (condom and diaphragm),
sterilisation, sexual abstinence) for the study duration and 5 months post-dosing.

10. Subject understands and voluntarily signs an ICF prior to any study-related
assessments/procedures are conducted.

11. Subject is able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

1. Having received 1 or more chemotherapy line for recurrent/metastatic disease

2. Any residual CTCAE grade ≥ 2 toxicity

3. Subject has any other malignancy within 3 years prior to randomization, with the
exception of adequately treated in situ carcinoma of the cervix, uteri, or
non-melanoma skin cancer (all treatment of which should have been completed 6 months
prior to enrolment), in situ squamous cell carcinoma of the breast, or incidental
prostate cancer T1a, Gleason < 7, PSA <10 ng/ml.

4. Subject has had radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2
weeks prior to starting IP, and/or from whom ≥ 30% of the bone marrow was irradiated.

5. Having participated in another clinical trial or having received any investigational
agent in the preceding 30 days before study entry.

6. Chronic systemic immunosuppressive therapy that cannot be interrupted during treatment
study.

7. Subject has significant active cardiac disease within the previous 6 months including
unstable angina or angina requiring surgical or medical intervention, significant
cardiac arrhythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart
failure.

8. Subject has a known or suspected hypersensitivity to study drugs.

9. Subject is pregnant or breast feeding.

10. Subject is receiving prohibited medication as per section 7.4.2 and suspension of such
treatment is considered unsafe.

11. Subject has history of prior or current osteonecrosis of the jaw (ONJ).

12. Subject has history of prior irradiation to the mandible, specified as:

Dose constraints to the mandible: Dmax = 70 Gy, V50 = 62 Gy and V60 = 20 Gy Mandible
should be contoured as whole organ, with alveolar bone, excluding teeth

13. Subject has any other concurrent severe and/or uncontrolled medical condition that
would, in the Investigator's judgment, contraindicate subject participation in the
clinical study.