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

NCT03923842 | Unknown Phase 2

• 1 other identifier: 2017-005017-31
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief 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

Conditions

Nasopharyngeal Carcinoma; EBV Related Carcinoma

Keywords

NPC; EBV

Outcome Measures

Primary Outcomes (1)

• plasmatic EBV DNA change

  Meaningful plasmatic EBV DNA change in circulating EBV DNA levels from baseline (prior to the first denosumab administration on day -15 with respect to first chemotherapy administration) to the third denosumab dose (denosumab day 16, equivalent to chemotherapy treatment day 1).

  change in circulating EBV DNA levels from baseline (prior to the first denosumab administration on day -15 with respect to first chemotherapy administration

Secondary Outcomes (1)

• Progression Free Survival

  PFS will be defined as the time from Chemotherapy treatment start (day1 for chemotherapy, day16 for denosumab) to disease progression or death from any cause.

Other Outcomes (5)

• Absolute change in cellular immunity to EBV

  prior to first denosumab administration, chemotherapy day -15 and denosumab day 1) and the subsequent planned time point (16 days, 2 and 6 months after denosumab treatment start

• Safety profile of denosumab plus chemotherapy: NCI CTCAE v 4.03

  During study treatment anf follow up period

• Absolute change in blood and salivary miRNA NPC profiles

  at 16 days, 2 and 6 months after Denosumab treatment start

Study Arms (2)

ARM A: Denosumab Treatment

EXPERIMENTAL

Denosumab 120 mg sc on day -15, -8 and day 1, followed by Denosumab 120 mg sc q4wks + platinum based drugs q3wks + Gemcitabine 1250 mg/sm day 1,8 q3wks for 6 cycles. Denosumab 120 mg sc q4wks will continue for 12 months since chemotherapy end.

Drug: Denosumab Inj 120 MG/1.7ML

ARM B Control Arm

ACTIVE COMPARATOR

platinum based drugs q3wks + Gemcitabine 1250 mg/sm day 1,8 q3wks for 6 cycles. At the end of the 6 cycles, if the patient is not progressing, can continue treatment with Gemcitabine alone.for 12 months

Drug: Chemotherapy as clinical standard of care

Interventions

Denosumab Inj 120 MG/1.7ML DRUG

Denosumab 120 mg sc on day -15, -8 and day 1, followed by Denosumab 120 mg sc q4wks + platinum based drugs q3wks + Gemcitabine 1250 mg/sm day 1,8 q3wks for 6 cycles. Denosumab 120 mg sc q4wks will continue for 12 months since chemotherapy end.

Also known as: Denosumab treatment

ARM A: Denosumab Treatment

Chemotherapy as clinical standard of care DRUG

platinum based drugs q3wks + Gemcitabine 1250 mg/sm day 1,8 q3wks for 6 cycles. Gemcitabine will continue for 12 months if the patient will not shown disease progression

Also known as: Standard of care treatment

ARM B Control Arm

Eligibility Criteria

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

You may qualify if:

• EBV related nasopharyngeal cancer
• Detectable and quantifiable plasmatic EBV DNA
• Recurrent and/or metastatic disease not suitable for curative treatment
• PS \< 2
• Suitable for polychemotherapy
• Age ≥ 18 years
• Informed consent signed
• Subject has adequate organ functions, evidenced by the following:
• AST (SGOT), ALT (SGPT) ≤ 2.5 x upper limit of normal range (ULN), or ≤ 5 x ULN range if liver metastasis present
• Total bilirubin ≤ 1.5 x ULN
• creatinine clearance 24/h \> 50 mL/min
• Total serum calcium \> 8.8 mg/dL
• Absolute neutrophil count ≥ 1.5 x 10\*9 cells/L
• Platelets ≥ 100 x 10\*9 cells/L
• Haemoglobin ≥ 9 g/dL

You may not qualify if:

• Having received 1 or more chemotherapy line for recurrent/metastatic disease
• Any residual CTCAE grade ≥ 2 toxicity
• 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.
• 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.
• Having participated in another clinical trial or having received any investigational agent in the preceding 30 days before study entry.
• Chronic systemic immunosuppressive therapy that cannot be interrupted during treatment study.
• 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.
• Subject has a known or suspected hypersensitivity to study drugs.
• Subject is pregnant or breast feeding.
• Subject is receiving prohibited medication as per section 7.4.2 and suspension of such treatment is considered unsafe.
• Subject has history of prior or current osteonecrosis of the jaw (ONJ).
• 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
• 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.

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead
• Mario Negri Institute for Pharmacological Research: collaborator

Study Sites (2)

ASST degli Spedali Civili di Brescia

Brescia, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale Tumori

Milan, 20126, Italy

NOT YET RECRUITING

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Paolo Bossi, Dr.

  Università degli Studi di Brescia ASST degli Spedali Civili di Brescia

  STUDY CHAIR

Central Study Contacts

Lital Hollander, manager

CONTACT

003939014640; lital.hollander@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: NN
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase II, 2:1 randomized, open label, and multicentre proof of principle trial with denosumab in patients with recurrent/metastatic (RM) NPC at first line systemic therapy.

Study Record Dates

• First Submitted: April 18, 2019
• First Posted: April 23, 2019
• Study Start: June 30, 2019
• Primary Completion: September 30, 2021
• Study Completion: October 30, 2022
• Last Updated: February 17, 2020

Record last verified: 2020-02

Locations

IT (2)