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

NCT03647839 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: CA209-99U
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 14

Brief Summary

This Phase II research project will test the efficacy, safety, and tolerability of an experimental drug combination: either nivolumab and BBI608 or nivolumab and BNC105 in patients with metastatic colorectal cancer who have previously failed standard of care treatment.

Conditions

Colorectal Cancer Metastatic

Keywords

Microsatellite stable tumour; Refractory colorectal cancer; Tumour microenvironment; Vascular Disrupting Agent; STAT3 inhibitors; PD1 inhibitors; Unresectable colorectal cancer; nivolumab; BNC105; BBI-608

Outcome Measures

Primary Outcomes (1)

• Objective response per iRECIST

  From start of treatment up to the date when the last patient has their 6 months follow-up assessment

Secondary Outcomes (4)

• Objective response per RECIST1.1

  From start of treatment up to the date when the last patient has their 6 months follow-up assessment

• Progression free survival (PFS).

  From start of treatment until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to the date when the last patient has their 6 months follow-up assessment

• Adverse event assessed using CTCAE version 5.0

  Through treatment completion, maximum of 2 years

• Overall survival

  From start of treatment until the date of death from any cause, assessed up to the date when the last patient has their 6 months follow-up assessment

Study Arms (2)

Arm 1

EXPERIMENTAL

Nivolumab and BNC105

Drug: Nivolumab 10 MG/ML; Drug: BNC 105

Arm 2

EXPERIMENTAL

Nivolumab and BBI-608

Drug: Nivolumab 10 MG/ML; Drug: BBI608

Interventions

Nivolumab 10 MG/ML DRUG

Nivolumab will be supplied free of charge by Bristol-Myers Squibb (BMS) as sterile liquid in 10mL glass vials.

Also known as: Opdivo

Arm 1; Arm 2

BNC 105 DRUG

BNC105 will be provided free of charge by Bionomics, as a sterile solution of BNC105P. BNC105P is a clear, colorless to yellow liquid presented in a clear glass vial and is intended to be diluted with commercially available sterile 0.9% saline prior to IV administration.

Arm 1

BBI608 DRUG

BBI-608 will be supplied free of charge by Boston Biomedical as capsules.

Also known as: Napabucasin

Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has a histological diagnosis of adenocarcinoma of colorectal origin.
• Has documented microsatellite stable tumour as assessed by PCR or IHC.
• Metastatic disease that is not resectable.
• Male or female patients \> 18 years of age at screening.
• Failed in any sequence or combination oxaliplatin, fluoropyrimidine, irinotecan with or without bevacizumab where failure is defined as progression or toxicity precluding further therapy.
• For patients with ras/b-raf wild type tumours: failed anti EGFR therapy (cetuximab and/or panitumumab) where failure is defined as progression or toxicity precluding further therapy. Patients with b-raf mutant tumours and/or right sided primary tumours may have received anti-EGFR therapy but this is not mandated.
• Patient has measurable disease according to RECIST 1.1.
• Metastatic lesion(s) amenable to biopsy, this cannot be the sole site of measurable disease.
• ECOG performance status 0 or 1.
• Adequate organ and hematologic function within 7 days of randomisation, defined by:
• Neutrophils \> 1.5 X 109/L
• Platelets \> 80 X 109/L
• Serum aspartate transaminase (AST) or alanine transaminase (ALT) \< 3 x upper limit of normal (ULN)
• Bilirubin \< 1.5 x ULN
• Albumin \>30g/L

You may not qualify if:

• Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol.
• Patients with any active, known, or suspected autoimmune disease, with the following exceptions:
• Patients with vitiligo, type 1 diabetes mellitus, resolved childhood asthma or atopy are permitted to enroll.
• Patients with suspected autoimmune thyroid disorders may be enrolled if they are currently euthyroid or with residual hypothyroidism requiring only hormone replacement.
• Patients with psoriasis requiring systemic therapy must be excluded from enrolment
• Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days of randomisation. Inhaled or topical steroids and adrenal replacement doses \> 10mg/day prednisone equivalents are permitted in the absence of active autoimmune disease.
• Patient has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Patients receiving long-term anti-coagulation or anti-platelet agents which cannot be ceased for an appropriate interval to allow mandatory tumour biopsies prior to and during therapy.
• Patient has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Has a known history of HIV (HIV 1/2 antibodies). Formal testing is only required if there is significant clinical suspicion of HIV.
• Known active brain metastases (unless adequately treated with surgery and/or radiotherapy \>30 d prior and asymptomatic).
• Significant vascular events within the previous 6 months (unstable angina, myocardial infarction, TIA, CVA).

Sponsors & Collaborators

• Australasian Gastro-Intestinal Trials Group: lead

Study Sites (14)

Border Cancer Hospital

Albury, New South Wales, 2640, Australia

Location

Newcastle Private Hospital

Newcastle, New South Wales, Australia

Location

Northern Cancer Institute

St Leonards, New South Wales, 2065, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Brisbane Hospital

Herston, Queensland, 4029, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Ashford Cancer Centre Research

Kurralta Park, South Australia, 5037, Australia

Location

Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Ballarat Health Service

Ballarat, Victoria, Australia

Location

Eastern Health

Box Hill, Victoria, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Olivia Newton-John Cancer Wellness and Research Centre

Heidelberg, Victoria, 3084, Australia

Location

Peninsula Health/Frankston Hospital

Mornington Peninsula, Victoria, Australia

Location

Western Health

Saint Albans, Victoria, 3021, Australia

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Nivolumab; BNC 105; napabucasin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Niall Tebbutt, Prof

  Olivia Newton-John Cancer Wellness and Research Centre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label, multicentre, parallel phase II study designed to assess the efficacy of the combination of nivolumab and BNC105 and the combination of nivolumab and BBI-608. Patients with microsatellite stable adenocarcinoma of colorectal origin that is not resectable are eligible and will be randomised in the ratio of 1:1 using permuted block randomisation with stratification by screening ECOG performance status (0 or 1) to receive either nivolumab and BNC105 or nivolumab and BBI-608.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: This is an open-label, multicentre, parallel phase II study designed to assess the efficacy of the combination of nivolumab and BNC105 and the combination of nivolumab and BBI-608. Patients with microsatellite stable adenocarcinoma of colorectal origin that is not resectable are eligible and will be randomised in the ratio of 1:1 using permuted block randomisation with stratification by screening ECOG performance status (0 or 1) to receive either nivolumab and BNC105 or nivolumab and BBI-608.

Study Record Dates

• First Submitted: July 2, 2018
• First Posted: August 27, 2018
• Study Start: September 6, 2018
• Primary Completion: January 29, 2021
• Study Completion: April 9, 2021
• Last Updated: August 27, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (14)