Assessing the validity of progression free survival in patients with hepatocellular carcinoma as an endpoint in clinical trials

Lead Investigator: Philip Johnson, University of Liverpool
Title of Proposal Research: Assessing the validity of progression free survival in patients with hepatocellular carcinoma as an endpoint in clinical trials
Vivli Data Request: 9019
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

We work on primary liver cancer, that is cancer that starts in the liver – also known as hepatocellular carcinoma (HCC). This is a common cancer (it is predicted by 2025 there will be >1 million cases) that is usually rapidly fatal. Its incidence is rising very fast. (We have published extensively in this area and references are available if required). Sometimes HCC can be cured by surgery but usually it is too advanced for surgery to be effective, by the time it is diagnosed.
In the absence of physical removal of the tumour by surgery or other methods we rely on other approaches such as chemotherapy or immunotherapy. Slow but steady progress is being made in this area. But the progress is impeded because of the cost and complicated nature of the clinical trials that need to be carried out before a new drug can be introduced.
In the field of clinical trials ‘Progression free survival’ (PFS) is a widely used measurement of the effectiveness of a new drug on a particular cancer within a clinical trial. We have major concerns about the validity of PFS:
a) In recent trials, the correlation between PFS and overall survival has been poor suggesting that PFS is not a good way to test a drug’s effectiveness.
b) The calculation of PFS appears to give variable results depending on the time during a trial at which it is assessed.
c) We have noted extreme variation in response to treatment of individual lesions (tumours) within the same organ.
We now seek access to existing clinical trial data in which serial examination of tumour sizes (and certain clinical variables) has been recorded together with reported PFS calculation and overall survival.
This research will establish if PFS is really a good way to measure the efficacy of a new cancer treatment. If this is not the case, then it could have a detrimental effect on patient care through the approval of drugs which may not actually be effective.
We plan to do this through the assessment of a series of simple plots which will show the change in the size of individual tumours in the liver of a patient over time. Therefore, it can be determined whether the behaviour of tumours in response to the same treatment in a patient is consistent over time.

Requested Studies:

A Phase III, Open-Label, Randomized Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
Data Contributor: Roche
Study ID: NCT03434379
Sponsor ID: YO40245

A Multicenter, Open Label, Phase I /Randomised Phase II Study to Evaluate Safety, Pharmacokinetics and Efficacy of BIBF 1120 in Comparison With Oral Sorafenib for Advanced Hepatocellular Carcinoma Patients.
Data Contributor: Boehringer Ingelheim
Study ID: NCT01004003
Sponsor ID: 1199.37

A Randomized, Multi-Center, Blinded, Placebo-Controlled Study Of Mapatumumab ([HGS1012], A Fully Monoclonal Antibody To TRAIL-R1) In Combination With Sorafenib As A First-Line Therapy In Subjects With Advanced Hepatocellular Carcinoma
Data Contributor: GSK
Study ID: NCT01258608
Sponsor ID: 200149

A Randomised, Double-blind, Parallel Group, Multi-centre, Phase II Study to Assess the Efficacy and Safety of Best Support Care (BSC) Plus ZD6474(Vandetanib) 300 mg, BSC Plus ZD6474(Vandetanib) 100 mg, and BSC Plus Placebo in Patients With Inoperable Hepatocellular Carcinoma (HCC)
Data Contributor: Sanofi
Study ID: NCT00508001
Sponsor ID: D4200C00072

An Open-label, Randomized Phase 3 Study of the Efficacy and Tolerability of Linifanib (ABT-869) Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma (HCC )
Data Contributor: AbbVie
Study ID: NCT01009593
Sponsor ID: NCT01009593