Colorectal Cancer MetastaticPhase 2MODULATENCT03647839
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
A Phase 2 study testing Nivolumab 10 MG/ML, BNC 105 and BBI608 in people with Colorectal Cancer Metastatic, run by Australasian Gastro-Intestinal Trials Group at 14 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer Metastatic
- What is being tested?
- Nivolumab 10 MG/ML, BNC 105 and BBI608
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 14 sitesAustralia
- Study dates
- 6 Sep 2018to 9 Apr 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- Creatinine clearance ≥ 50ml/min(Cockcroft-Gault).
- Life expectancy of at least 12 weeks
- No other concurrent uncontrolled medical conditions
- No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer treated with curative intent >2 years previously without evidence of relapse.
- Female patients of childbearing potential should have a negative urine or serum pregnancy within 24 hours prior to randomisation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female patients of childbearing potential should be willing to use a reliable method of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 180 days after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Male patients with female partners of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.
- Patient has provided written informed consent including consent for tumour biopsies and donation of tumour tissue for biomarker studies.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
Australia14 sites
Border Cancer Hospital
Albury, New South Wales, 2640
Ballarat Health Service
Ballarat, Victoria
Flinders Medical Centre
Bedford Park, South Australia, 5042
Eastern Health
Box Hill, Victoria
Monash Health
Clayton, Victoria, 3168
Olivia Newton-John Cancer Wellness and Research Centre
Heidelberg, Victoria, 3084
Royal Brisbane Hospital
Herston, Queensland, 4029
Ashford Cancer Centre Research
Kurralta Park, South Australia, 5037
Peninsula Health/Frankston Hospital
Mornington Peninsula, Victoria
Newcastle Private Hospital
Newcastle, New South Wales
Western Health
Saint Albans, Victoria, 3021
Northern Cancer Institute
St Leonards, New South Wales, 2065
Westmead Hospital
Westmead, New South Wales, 2145
Queen Elizabeth Hospital
Woodville South, South Australia, 5011
About this study
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.
Read the detailed description
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.
The expected sample size is 90 patients over a 24 month recruitment period.
- Conditions
- Colorectal Cancer Metastatic
- Being tested
- Nivolumab 10 MG/ML, BNC 105, BBI608
- Keywords
- Microsatellite stable tumour, Refractory colorectal cancer, Tumour microenvironment, Vascular Disrupting Agent, STAT3 inhibitors, PD1 inhibitors, Unresectable colorectal cancer, nivolumab, BNC105, BBI-608
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab 10 MG/MLDrug
Also called Opdivo
Nivolumab will be supplied free of charge by Bristol-Myers Squibb (BMS) as sterile liquid in 10mL glass vials.
BNC 105Drug
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.
BBI608Drug
Also called Napabucasin
BBI-608 will be supplied free of charge by Boston Biomedical as capsules.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Nivolumab and BNC105 Receives: Drug: Nivolumab 10 MG/ML; Drug: BNC 105 |
| Arm 2 | Experimental | Nivolumab and BBI-608 Receives: Drug: Nivolumab 10 MG/ML; Drug: BBI608 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response per iRECIST
Measured: 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
Measured: From start of treatment up to the date when the last patient has their 6 months follow-up assessment
Progression free survival (PFS).
Measured: 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
Measured: Through treatment completion, maximum of 2 years
Overall survival
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2018
- Study start6 Sep 2018
- Primary completion29 Jan 2021
- Study completion9 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Australasian Gastro-Intestinal Trials Group
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Niall Tebbutt, Prof, Study chair, Olivia Newton-John Cancer Wellness and Research Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03647839
- Sponsor's protocol ID
- CA209-99U
- Acronym
- MODULATE
- Status last verified
- Aug 2021
- First submitted
- 2 Jul 2018
- Last updated
- 27 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared.
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03647839
- Acronym / sponsor ID
- MODULATE / CA209-99U
- Conditions
- Colorectal Cancer Metastatic
- Keywords
- Microsatellite stable tumour, Refractory colorectal cancer, Tumour microenvironment, Vascular Disrupting Agent, STAT3 inhibitors, PD1 inhibitors, Unresectable colorectal cancer, nivolumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Australasian Gastro-Intestinal Trials GroupResearch network
- Study start
- 6 Sep 2018 (actual)
- Primary completion
- 29 Jan 2021 (actual)
- Study completion
- 9 Apr 2021 (actual)
- First posted
- 27 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
The expected sample size is 90 patients over a 24 month recruitment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Nivolumab 10 MG/ML, Drug: BNC 105Nivolumab and BNC105 |
| Arm 2 | Experimental | Drug: Nivolumab 10 MG/ML, Drug: BBI608Nivolumab and BBI-608 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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.
Key exclusion criteria (14 listed)
- 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 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nivolumab 10 MG/MLAlso: OpdivoNivolumab will be supplied free of charge by Bristol-Myers Squibb (BMS) as sterile liquid in 10mL glass vials. | Drug | Arm 1, Arm 2 |
| BNC 105BNC105 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. | Drug | Arm 1 |
| BBI608Also: NapabucasinBBI-608 will be supplied free of charge by Boston Biomedical as capsules. | Drug | Arm 2 |
Primary outcome
Objective response per iRECIST
Time frame: From start of treatment up to the date when the last patient has their 6 months follow-up assessment
4 secondary outcomes
Objective response per RECIST1.1
Time frame: From start of treatment up to the date when the last patient has their 6 months follow-up assessment
Progression free survival (PFS).
Time frame: 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
Time frame: Through treatment completion, maximum of 2 years
Overall survival
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2021.
- Individual participant dataSharing planned: No. Individual participant data will not be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Niall Tebbutt, Prof study chair
Olivia Newton-John Cancer Wellness and Research Centre
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab 10 MG/ML, BNC 105 and BBI608 in people with Colorectal Cancer Metastatic, run by Australasian Gastro-Intestinal Trials Group at 14 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response per iRECIST (time frame: From start of treatment up to the date when the last patient has their 6 months follow-up assessment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2021.