MODULATE

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Trial Status

In Follow-up

Cancer Type

Colorectal Cancer

AIM

This study aims to test whether it is possible to reverse the resistance of MSS colorectal cancer to PD1 inhibition by combining the PD1 inhibitor nivolumab with other drugs designed to stimulate lymphocyte infiltration of tumours.

Two approaches will be tested (1) an inhibitor of the signalling protein STAT3 and (2) a vascular disrupting agent which blocks the blood supply of cancers.  Animal/laboratory studies suggest that targeting STAT3 or using vascular disrupting agents will improve lymphocyte infiltration into cancers, but this has not been proven in human studies.

SUMMARY

MODULATE is a prospective randomised study that will recruit 90 patients with advanced MSS colorectal cancer at approximately 15 sites in Australia. The study will recruit patients with advanced colorectal cancer who have received and failed all standard treatments.

It is hoped that these approaches will benefit patients but this is unknown.  The approaches are highly experimental, but there is no placebo or control arm.

Participating Centres

New South Wales
Westmead Hospital
Northern Cancer Institute
Newcastle Private Hospital
Border Medical Oncology
Queensland
Royal Brisbane and Womens Hospital
South Australia
Queen Elizabeth Hospital
Ashford Cancer Centre
Flinders Medical Centre
Tasmania
Royal Hobart Hospital
Victoria
Austin Health
Western Health-Sunshine Hospital
Monash Medical Centre
Ballarat Oncology & Haematology Services
Peninsula Health, Frankston Hospital
Box Hill Hospital/Eastern Health

Trial Status

In Follow-up

Cancer Type

Colorectal Cancer

Protocol Title

Modulation of the tumour microenvironment using either vascular disrupting agents or STAT3 inhibition in order to synergise with PD1 inhibition in microsatellite stable, refractory colorectal cancer

AIM

Primary Objective:

  • To determine the response rate (Immune RECIST)

Secondary Objective:

  • To determine treatment related toxicity
  • To determine progression free survival
  • To determine overall survival
  • Exploratory studies of biomarkers

BACKGROUND

Colorectal cancer is the most commonly diagnosed cancer in the Australian population. Surgery, with or without chemotherapy and radiotherapy, can be used to cure colorectal cancer that is diagnosed early. However, cases of advanced colorectal cancer where it has spread to other organs usually cannot be cured. Advanced colorectal cancer is treated with chemotherapy and other drugs, known as targeted therapies.  This can control advanced colorectal cancer for a limited time, but inevitably these cancers will evolve to become resistant to all the standard treatments available.  By the time cancers progress to this stage, survival is poor and patients are increasingly symptomatic.  Additional therapies are therefore needed to further extend survival of patients with advanced colorectal cancer.

CLINICAL TRIAL DESIGN

This study is a prospective randomised study that will recruit 90 patients with advanced MSS colorectal cancer at approximately 15 sites in Australia. The study will recruit patients with advanced colorectal cancer who have received and failed all standard treatments.  It is hoped that these approaches will benefit patients but this is unknown.  The approaches are highly experimental, but there is no placebo or control arm.

Arm 1:

  • Nivolumab (240mg every 14 days)
  • BNC105 (16mg/m2/day on day 1 and 8 every 21 days)

For 24 months or until disease progression or unacceptable toxicity.

Arm 2:

  • Nivolumab (240mg every 14 days)
  • BBI608 (240mg bd continuous)

For 24 months or until disease progression or unacceptable toxicity.

Patients Recruited

Click to access the table and view recruitment data on all AGITG open trials:

Open Trial Recruitment Table

Participating Centres

New South Wales
Westmead Hospital
Northern Cancer Institute
Newcastle Private Hospital
Border Medical Oncology
Queensland
Royal Brisbane and Womens Hospital
South Australia
Queen Elizabeth Hospital
Ashford Cancer Centre
Flinders Medical Centre
Tasmania
Royal Hobart Hospital
Victoria
Austin Health
Western Health-Sunshine Hospital
Monash Medical Centre
Ballarat Oncology & Haematology Services
Peninsula Health, Frankston Hospital
Box Hill Hospital/Eastern Health

Principal Investigator

A/Professor Niall Tebbutt

Detailed Information

More information available online at the ClinicalTrials.gov, Identifier: NCT03647839. Click here for more.

Funding

Bristol-Myers Squibb