Systemic Therapy and Chemoradiation in Advanced Localised Pancreatic Cancer - 2

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.

Conditions

• Pancreatic Neoplasms (Locally Advanced Non-metastatic)

Interventions

DRUG

nab-paclitaxel

Abraxane is a proprietary solvent-free, protein-stabilized formulation of paclitaxel comprised of paclitaxel and human albumin in a noncrystalline amorphous state

RADIATION

60Gy in 30#

RADIATION

50.4Gy in 28#

DRUG

Nelfinavir

VIRACEPT® (nelfinavir mesylate) is an inhibitor of the human immunodeficiency virus (HIV) protease.

DRUG

Capecitabine

Given in combination with gemcitabine, known as GemCap.

DRUG

Gemcitabine

Gemcitabine is indicated for treatment of patients with locally advanced or metastatic adenocarcinoma of the pancreas. It is administered as an infusion

Sponsors & Collaborators

• Celgene

  collaborator INDUSTRY

• Cancer Research UK

  collaborator OTHER

• University of Oxford

  lead OTHER

Principal Investigators

• Somnath Mukherjee, MD, FRCP, FRCR · [email protected]

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-03-31

Primary Completion

2021-06-23

Completion

2021-06-23

Countries

• United Kingdom

Study Locations