Clinical trial NCT02024009: Systemic Therapy and Chemoradiation in Advanced Localised Pancreatic Cancer - 2
Official title: A Multi-centre Randomised Study of Induction Chemotherapy Followed by Capecitabine (+/-Nelfinavir) With High or Standard Dose Radiotherapy for Locally Advanced Non-metastatic Pancreatic Cancer
Conditions: Pancreatic Neoplasms (Locally Advanced Non-metastatic)
Summary: This study will evaluate the role of increasing radiotherapy dose and addition of nelfinavir to chemoradiotherapy (CRT) in patients with inoperable pancreatic cancer that has not spread beyond the pancreas.
Currently in the United Kingdom (UK), either chemotherapy alone or chemotherapy followed by CRT can be used in the management of inoperable pancreatic cancer that has not spread. CRT consists of 25-30 radiotherapy treatments in combination with chemotherapy. Although this treatment is effective in controlling local symptoms and slowing down the pace of cancer, in most cases it is unable to shrink it enough to make it operable. Some of the reasons for this could be the lack of oxygen and lack of blood flow within the tumour making it resistant to the effects of CRT. This study will investigate whether increasing the dose of radiotherapy, or increasing the oxygen and blood supply to the tumour by giving nelfinavir, or a combination of both, can improve outcomes. We also want to know what the additional toxicities from such intensive approaches are.
All participants will initially receive 12 weeks of chemotherapy, and those with stable or responding disease will receive further study treatment. The treatment allocation, initially to one of the four options, but as of 26Feb2020, to one of two options, as outlined below will be done at random by computer and neither the doctor nor the patient can choose the treatment option. The process of randomisation ensures that all treatment arms are equally balanced in terms of patient and tumour characteristics, and to reduce the possibility of bias.
The study will consist of 2 stages. In the 1st stage we aimed to find the right dose of nelfinavir to combine with CRT, requiring 27 participants of whom up to 18 will receive nelfinavir together with CRT. The Maximum Tolerated Dose of nelfinavir for Stage 2 has been established as 1250mg bd based on the data of 4 patients in the Stage 1, 1250mg cohort. In the 2nd stage, we want to find out the benefits of this approach over and above standard treatments and therefore we will recruit the order of 168 participants and allocate 96 to 1 of the 4 following treatment arms (As from 26Feb2020, randomisation will continue into one of two arms):
Arm A: Nelfinavir together with CRT (arm A closed on 26Feb2020) Arm B: CRT (without nelfinavir) Arm C: Nelfinavir together with CRT (but using a higher than conventional dose of radiotherapy) (arm C closed on 26Feb2020) Arm D: CRT without nelfinavir (but using a higher than conventional dose of radiotherapy) Participants allocated to any of the two arms, following closure of Arms A & C on 26Feb2020, will receive one further cycle of chemotherapy prior to starting chemoradiotherapy (without nelfinavir). This is to allow time for radiotherapy planning.
Participants who are ineligible or refuse randomisation will be treated as per local standard but will remain in the study for follow up every 12 weeks. Their data will contribute to an Overall Survival (OS) analysis.
Interventions:
description: Abraxane is a proprietary solvent-free, protein-stabilized formulation of paclitaxel comprised of paclitaxel and human albumin in a noncrystalline amorphous state
name: nab-paclitaxel
other_name: Abraxane
type: Drug
name: 60Gy in 30#
type: Radiation
name: 50.4Gy in 28#
type: Radiation
description: VIRACEPT® (nelfinavir mesylate) is an inhibitor of the human immunodeficiency virus (HIV) protease.
name: Nelfinavir
other_name: Viracept
type: Drug
description: Given in combination with gemcitabine, known as GemCap.
name: Capecitabine
type: Drug
description: Gemcitabine is indicated for treatment of patients with locally advanced or metastatic adenocarcinoma of the pancreas. It is administered as an infusion
name: Gemcitabine
other_name: GEMZAR
type: Drug
Study arms:
design_group_description: 12 weeks (3 cycles) of induction Gemcitabine and Nab-paclitaxel (GEMABX) chemotherapy then 1 cycle of GEMABX* whilst radiotherapy (RT) planned then capecitabine (830mg/m2 oral bd) + Nelfinavir** + 50.4 Grays (Gy) in 28# (arm A closed on 26Feb2020 due to lack of efficacy of nelfinavir)<br/>*1 cycle GEMABX = 28 day cycle of intravenous Abraxane 125mg/m2 followed by gemcitabine 1000mg/m2 on day 1, 8 and 15.
design_group_title: Arm A
design_group_type: Experimental
design_group_description: 12 weeks (3 cycles) of induction GEMABX chemotherapy then 1 cycle of GEMABX* whilst RT planned then capecitabine (830mg/m2 oral bd) + 50.4Gy in 28#<br/>*1 cycle GEMABX = 28 day cycle of intravenous Abraxane 125mg/m2 followed by gemcitabine 1000mg/m2 on day 1, 8 and 15.
design_group_title: Arm B
design_group_type: Experimental
design_group_description: 12 weeks (3 cycles) of induction GEMABX chemotherapy then<br/>1 cycle of GEMABX* whilst RT planned then capecitabine (830mg/m2 oral bd) + Nelfinavir** + 60Gy in 30# (arm C closed on 26Feb2020 due to lack of efficacy of nelfinavir)<br/>*1 cycle GEMABX = 28 day cycle of intravenous Abraxane 125mg/m2 followed by gemcitabine 1000mg/m2 on day 1, 8 and 15
design_group_title: Arm C
design_group_type: Experimental
design_group_description: 12 weeks (3 cycles) of induction GEMABX chemotherapy then<br/>1 cycle of GEMABX* whilst RT planned then capecitabine (830mg/m2 oral bd) + 60Gy in 30#<br/>*1 cycle GEMABX = 28 day cycle of intravenous Abraxane 125mg/m2 followed by gemcitabine 1000mg/m2 on day 1, 8 and 15.
design_group_title: Arm D
design_group_type: Experimental
Sponsor: University of Oxford
Collaborators: Celgene Corp.
Cancer Research UK
Drug name mappings:
name: 白蛋白结合型紫杉醇
lang: CN
name: Albumin-Bound Paclitaxel
lang: EN
name: パクリタキセル(JAN)
lang: JP
name: 盐酸吉西他滨
lang: CN
name: Gemcitabine Hydrochloride
lang: EN
name: ゲムシタビン塩酸塩
lang: JP
name: 甲磺酸奈非那韦
lang: CN
name: Nelfinavir Mesylate
lang: EN
name: ネルフィナビルメシル酸塩
lang: JP
name: 卡培他滨
lang: CN
name: Capecitabine
lang: EN
name: カペシタビン
lang: JP