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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03647839




Registration number
NCT03647839
Ethics application status
Date submitted
2/07/2018
Date registered
27/08/2018
Date last updated
27/08/2021

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
CA209-99U
Universal Trial Number (UTN)
Trial acronym
MODULATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer Metastatic 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nivolumab 10 MG/ML
Treatment: Drugs - BNC 105
Treatment: Drugs - BBI608

Experimental: Arm 1 - Nivolumab and BNC105

Experimental: Arm 2 - Nivolumab and BBI-608


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

Treatment: Drugs: BNC 105
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.

Treatment: Drugs: BBI608
BBI-608 will be supplied free of charge by Boston Biomedical as capsules.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective response per iRECIST
Timepoint [1] 0 0
From start of treatment up to the date when the last patient has their 6 months follow-up assessment
Secondary outcome [1] 0 0
Objective response per RECIST1.1
Timepoint [1] 0 0
From start of treatment up to the date when the last patient has their 6 months follow-up assessment
Secondary outcome [2] 0 0
Progression free survival (PFS).
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Adverse event assessed using CTCAE version 5.0
Timepoint [3] 0 0
Through treatment completion, maximum of 2 years
Secondary outcome [4] 0 0
Overall survival
Timepoint [4] 0 0
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

Eligibility
Key inclusion criteria
1. Patient has a histological diagnosis of adenocarcinoma of colorectal origin.

2. Has documented microsatellite stable tumour as assessed by PCR or IHC.

3. Metastatic disease that is not resectable.

4. Male or female patients > 18 years of age at screening.

5. Failed in any sequence or combination oxaliplatin, fluoropyrimidine, irinotecan with
or without bevacizumab where failure is defined as progression or toxicity precluding
further therapy.

6. 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.

7. Patient has measurable disease according to RECIST 1.1.

8. Metastatic lesion(s) amenable to biopsy, this cannot be the sole site of measurable
disease.

9. ECOG performance status 0 or 1.

10. Adequate organ and hematologic function within 7 days of randomisation, defined by:

1. Neutrophils > 1.5 X 109/L

2. Platelets > 80 X 109/L

3. Serum aspartate transaminase (AST) or alanine transaminase (ALT) < 3 x upper
limit of normal (ULN)

4. Bilirubin < 1.5 x ULN

5. Albumin >30g/L

6. Creatinine clearance = 50ml/min(Cockcroft-Gault).

11. Life expectancy of at least 12 weeks

12. No other concurrent uncontrolled medical conditions

13. 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.

14. 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

15. 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.

16. 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.

17. Patient has provided written informed consent including consent for tumour biopsies
and donation of tumour tissue for biomarker studies.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Medical or psychiatric conditions that compromise the patient's ability to give
informed consent or to complete the protocol.

2. Patients with any active, known, or suspected autoimmune disease, with the following
exceptions:

1. Patients with vitiligo, type 1 diabetes mellitus, resolved childhood asthma or
atopy are permitted to enroll.

2. Patients with suspected autoimmune thyroid disorders may be enrolled if they are
currently euthyroid or with residual hypothyroidism requiring only hormone
replacement.

3. Patients with psoriasis requiring systemic therapy must be excluded from
enrolment

3. 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.

4. Patient has evidence of interstitial lung disease or active, non-infectious
pneumonitis.

5. Has an active infection requiring systemic therapy.

6. 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.

7. 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.

8. 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).

9. Has a known history of HIV (HIV 1/2 antibodies). Formal testing is only required if
there is significant clinical suspicion of HIV.

10. Known active brain metastases (unless adequately treated with surgery and/or
radiotherapy >30 d prior and asymptomatic).

11. Significant vascular events within the previous 6 months (unstable angina, myocardial
infarction, TIA, CVA).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/09/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/04/2021
Sample size
Target
Accrual to date
Final
90
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Border Cancer Hospital - Albury
Recruitment hospital [2] 0 0
Newcastle Private Hospital - Newcastle
Recruitment hospital [3] 0 0
Northern Cancer Institute - St Leonards
Recruitment hospital [4] 0 0
Westmead Hospital - Westmead
Recruitment hospital [5] 0 0
Royal Brisbane Hospital - Herston
Recruitment hospital [6] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [7] 0 0
Ashford Cancer Centre Research - Kurralta Park
Recruitment hospital [8] 0 0
Queen Elizabeth Hospital - Woodville South
Recruitment hospital [9] 0 0
Ballarat Health Service - Ballarat
Recruitment hospital [10] 0 0
Eastern Health - Box Hill
Recruitment hospital [11] 0 0
Monash Health - Clayton
Recruitment hospital [12] 0 0
Olivia Newton-John Cancer Wellness and Research Centre - Heidelberg
Recruitment hospital [13] 0 0
Peninsula Health/Frankston Hospital - Mornington Peninsula
Recruitment hospital [14] 0 0
Western Health - Saint Albans
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
- Newcastle
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
4029 - Herston
Recruitment postcode(s) [6] 0 0
5042 - Bedford Park
Recruitment postcode(s) [7] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [8] 0 0
5011 - Woodville South
Recruitment postcode(s) [9] 0 0
- Ballarat
Recruitment postcode(s) [10] 0 0
- Box Hill
Recruitment postcode(s) [11] 0 0
3168 - Clayton
Recruitment postcode(s) [12] 0 0
3084 - Heidelberg
Recruitment postcode(s) [13] 0 0
- Mornington Peninsula
Recruitment postcode(s) [14] 0 0
3021 - Saint Albans

Funding & Sponsors
Primary sponsor type
Other
Name
Australasian Gastro-Intestinal Trials Group
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03647839
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Niall Tebbutt, Prof
Address 0 0
Olivia Newton-John Cancer Wellness and Research Centre
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03647839