Neoplasms

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

All Conditions

Rare Diseases

Nasopharyngeal Carcinoma

Nasopharyngeal Neoplasms

Carcinoma

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Bevacizumab

Pembrolizumab

Cisplatin

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Immune Checkpoint Inhibitors

Each treatment cycle is 3 weeks. All patients would receive 3 cycles of induction chemotherapy as part of the study, and would then be considered for subsequent concurrent chemoradiotherapy at the investigator's discretion. Cross over is not allowed.

Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2

cisplatin and gemcitabine

Day -7 (+/-1 day): IV bevacizumab 7.5mg/kg diluted in normal saline over 30 minutes Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2+ IV pembrolizumab 200mg over 30 minutes Day 8: IV Gemcitabine 1000mg/m2 Day 15 (for cycles 1 and 2 only): IV bevacizumab 7.5mg/kg diluted in normal saline over 30 minutes

induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab.

Wan Qin Chong, MBBS, MRCP, M Med

Wan Qin Chong, MBBS, MRCP, MMed

Wan Qin Chong

Boon Cher Goh

Ross Soo

Yugarajah Asokumaran

Jia Li Low

Robert John Walsh

Rachel Wong

Kenneth Sooi

Silvana Wijaya

Jerold Low

Choon Seong Ang

Seng Wee Cheo

Qin Jian Low

Joshua Tay

Donovan Eu

The investigators hypothesize that the addition of bevacizumab and pembrolizumab to induction cisplatin and gemcitabine is tolerable and improves metabolic complete response (mCR), relapse free survival (RFS) and overall survival (OS) compared to induction cisplatin and gemcitabine in patients with locally advanced nasopharyngeal cancer (NPC)

NPC is endemic in Singapore and southern China, where the southern Chinese have the highest incidence of NPC worldwide.

Nasopharyngeal cancer usually presents as locally advanced stage III or IV disease with T3-4 or N2-3 nodal status.The standard of care of patients with locally advanced NPC is concurrent cisplatin chemotherapy with radiation therapy. However, a significant proportion of patients (about 30% in most randomised phase III studies) still relapse, compromising their survival from NPC. This is particularly so in patients with stage IVA, T4 or N3 NPC. Emerging evidence suggests induction chemotherapy improves patient survival in this group of patients when integrated with concurrent chemoradiation. A meta-analysis also showed that the addition of induction chemotherapy improved overall survival, and reduced locoregional and distant failure.

Dysregulation of the vascular endothelial growth factor (VEGF)/VEGF receptor-2 axis is a feature of many cancers including NPC. Elevated VEGF expression promotes disorganised tumour neovascularisation with hyperpermeable, tortuous capillaries.9, 10 Leakiness of vessels increases interstitial fluid pressure that collapses vessels with the collective effect of compromising blood flow and perfusion, limiting the delivery of therapeutic drugs. Furthermore, tumour expression of VEGF promotes immune tolerance directly and through hypoxic mechanisms.11 The VEGF/VEGFR-2 axis can be inhibited humanised monoclonal antibody bevacizumab, which binds to VEGF-A and prevents ligand-receptor engagement.

As NPC is associated with EBV antigen expression and is characterised by a prominent inflammatory infiltrate (inflammatory immune phenotype), there has been great interest in studying the effect of immune checkpoint inhibitors in NPC. Recently, the addition of 2 antiPD1 monoclonal antibodies, toripalimab 12 and camrelizumab 13, to cisplatin and gemcitabine was studied in 2 phase III trials conducted in mainland China. Both studies demonstrated that addition of antiPD1 therapy to cisplatin/gemcitabine chemotherapy improved the response rate, PFS and the duration of response in treatment naïve patients with metastatic or recurrent NPC.

The investigators have conducted a prior study evaluating pembrolizumab with and without bevacizumab. Preliminary analysis showed a higher response rate for addition of bevacizumab to pembrolizumab compared to pembrolizumab alone arm with no new safety signal. Importantly, the adverse effects of anti-angiogenic and anti PD1 therapy in humans are non-overlapping with cytotoxic chemotherapy. In view of this, we are conducting an open label, phase II randomised controlled trial comparing induction cisplatin, gemcitabine, bevacizumab and pembrolizumab with the standard arm (induction cisplatin and gemcitabine) in patients with stage III-IVA locally advanced EBER positive nasopharyngeal carcinoma.

This will be a single-centre, open label, randomised phase II study of induction cisplatin and gemcitabine with or without bevacizumab in patients with locally advanced or metastatic NPC. 50 Eligible patients will be randomised 1:1 into either of the two study arms: induction chemotherapy cisplatin and gemcitabine, or induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab.

Phase II Randomised Trial of Induction Gemcitabine and Cisplatin Versus Gemcitabine, Cisplatin, Pembrolizumab and Bevacizumab (GPPB) in Nasopharyngeal Cancer

National University Hospital, Singapore

Cholangiocarcinoma

Adenocarcinoma

Bile Duct Cancer

Patients after resection of cholangiocellular carcinoma will be allocated to treatment with cisplatin plus gemcitabine.

Cisplatin 25 mg/m2 days 1 and 8; next cycle starting day 22. Gemcitabine 1000 mg/m2 days 1 and 8; next cycle starting day 22. Total of 8 cycles.

Cisplatin and Gemcitabine

01 Studienregister MasterAdmins

OBJECTIVES

Primary objective:

The primary objective of the trial is to determine the safety of adjuvant treatment with cisplatin plus gemcitabine for a period of 6 months after curative resection of cholangiocellular carcinoma

Secondary objectives:

Secondary objectives of the trial are to assess the feasibility and efficacy of the adjuvant therapy and to determine duration of response and patterns of failure compared to historical controls without postoperative treatment

Exploratory objectives:

To obtain blood samples and tumor tissue after resection for establishment and characterization of new cholangiocarcinoma cell lines and tumor antigens. Other aims are identification of tumor specific antibodies from blood samples, and characterization of tumor antigens with consecutive development of new specific immunological therapies, e.g. cancer-testis antigens (CTA) for tumor vaccination.

* Trial with medicinal product

Adjuvant Cisplatin Plus Gemcitabine in Operable Cholangiocellular Carcinoma.

Adjuvant Treatment of Resectable Cholangiocellular Carcinoma (CCC) With Cisplatin Plus Gemcitabine. A Prospective Single Center Phase Ib-II Study.

University of Zurich

Prof. Dr. med.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase II Randomised Trial of Induction Gemcitabine and Cisplatin Versus Gemcitabine, Cisplatin, Pembrolizumab and Bevacizumab (GPPB) in Nasopharyngeal Cancer	NCT05305131	Nasopharyngeal ...	cisplatin and g... induction chemo...	21 Months - 99 Years	National University Hospital, Singapore
Adjuvant Cisplatin Plus Gemcitabine in Operable Cholangiocellular Carcinoma.	NCT01073839	Cholangiocellul...	Cisplatin and G...	18 Years -	University of Zurich
Adjuvant Cisplatin Plus Gemcitabine in Operable Cholangiocellular Carcinoma.	NCT01073839	Cholangiocellul...	Cisplatin and G...	18 Years -	University of Zurich
Adjuvant Cisplatin Plus Gemcitabine in Operable Cholangiocellular Carcinoma.	NCT01073839	Cholangiocellul...	Cisplatin and G...	18 Years -	University of Zurich

Spots Global Cancer Trial Database for cisplatin and gemcitabine