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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/NCT02726334




Registration number
NCT02726334
Ethics application status
Date submitted
28/03/2016
Date registered
1/04/2016
Date last updated
16/01/2019

Titles & IDs
Public title
A Phase I, Dose Escalation Study of BNC101 in Patients With Metastatic Colorectal Cancer.
Scientific title
A Phase I, Dose Escalation Study of BNC101 (Anti-LGR5 Humanized Monoclonal Antibody) in Patients With Metastatic Colorectal Cancer.
Secondary ID [1] 0 0
BNC101. 001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 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 - BNC101 Solution for Infusion
Treatment: Drugs - BNC101 in combination with FOLFIRI

Experimental: Group/Stream 1 - Monotherapy - Patient group: Patients who have failed at least two lines of chemotherapy for metastatic disease.
Treatment: BNC101 administered via intravenous infusion over 60 minutes weekly.
Patients with stable disease or a response at or after day 56 (2 cycles) will be allowed to continue to receive weekly doses of BNC101 until disease progression.

Experimental: Group/Stream 2 - Combination Chemo - Patient Group: Patients who have failed at least one line of chemotherapy for metastatic disease.
Treatment: BNC101 administered in combination with FOLFIRI
Participants will be treated until disease progression, intolerable toxicity, withdrawal of consent, or study termination by the Sponsor, whichever occurs first.


Treatment: Drugs: BNC101 Solution for Infusion
Administration: Administered via IV infusion once a week over 60 minutes (1 hour).

Treatment: Drugs: BNC101 in combination with FOLFIRI
BNC101 - Starting dose as determined by Arm A portion (one dose level below recommended Phase 2 dose).
BNC101 Administration: Administered via IV Infusion once a week over 60 minutes (1 hour).
FOLFIRI components:
Irinotecan (IRI) - Starting dose 180 mg/m2 (over 90 minutes on Day 1) Leucovorin (LV) - Starting dose 400 mg/m2 (administered over 120 minutes on Day 1 concurrently with IRI) 5-FU bolus - Starting dose 400 mg/m2 (administered after LV on Day 1, then) 5-FU infusion - Starting dose 2400 mg/m2 (administered over 48 hours starting on Day 1)
FOLFIRI Cycles are repeated every 14 days.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose
Timepoint [1] 0 0
DLT period of 28 days per dose level

Eligibility
Key inclusion criteria
1. Signed written Informed Consent

2. Age > 18 years

3. Eastern Cooperative Oncology Group (ECOG) score 0 - 1.

4. Histologically or cytologically confirmed colorectal cancer patients who have failed
at least 2 lines of chemotherapy (monotherapy treatment cohorts) or at least 1 line of
chemotherapy (combination treatment cohorts) for metastatic disease, and in the
opinion of both physician and patient it is not unreasonable to try experimental
therapy. Adjuvant FOLFOX within the last 6 months is considered a line of therapy. A
maintenance strategy post 1st line treatment is not considered as an additional line
of therapy.

5. Patients must have accessible tumor lesions amenable to biopsy which would not put the
patient or their treatment at risk. Patients in monotherapy escalation cohort 3 and
onwards, the monotherapy expansion cohort, and all combination treatment patients,
agree and are willing to provide 2 serial tumor lesion biopsies (a minimum of 2 fresh
cores/punches preferred whenever possible). Biopsies can be from liver metastases, in
lieu of the primary tumor. The presence of tumor tissue in fresh biopsies is to be
certified by a trained pathologist using appropriate extemporaneous histology or
cytology procedures. Refer to Appendix 6 for biopsy procedures.

6. All AEs of any prior chemotherapy, surgery, or radiotherapy, must have resolved to
Grade = 1.

7. Measurable or evaluable disease per RECIST version 1.1.

8. No known brain metastases (see also exclusion criterion No. 10).

9. Life expectancy of at least > 12 weeks.

10. Normal organ and marrow function:

1. Absolute neutrophil count (ANC) > 1,500/mL without growth factor support in the
past 14 days prior to enrolment

2. Platelets > 100,000/mL without transfusions in the past 14 days prior to
enrolment

3. Hemoglobin > 9.0 g/dL - Patients may be transfused or receive erythropoietic
treatment to meet this criterion

4. Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (< 2 x ULN for
subjects with Gilbert's syndrome)

5. Serum albumin = 3 g/dL.

11. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase, SGOT) and
alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase, SGPT) < 2.5 x
institutional ULN (for subjects with hepatic involvement < 5 x institutional ULN but
cannot be associated with elevated bilirubin).

12. Alkaline phosphatase (AlkPhos) > 2.5 x ULN, except in patients with documented liver
or bone metastases, where it can be < 5 x ULN.

13. For patients receiving biopsies, prothrombin time (PT) and activated partial
thromboplastin time (APTT)/international normalized ratio (INR) within normal limits
(± 15%)..

14. Creatinine < 1.5 x institutional ULN OR Creatinine clearance > 60 mL/min/1.73 m2 for
subjects with creatinine levels above institutional normal based on the Cockroft-Gault
glomerular filtration rate estimation:

(140 - age) x (weight in kg) x (0.85 if female)

72 x (serum creatinine in mg/dL)

(NOTE: For patients with a Body Mass Index (BMI) > 30 kg/m2, lean body weight should be
used instead)

15. No clinically significant abnormalities in urinalysis results (obtained = 14 days prior
to enrolment).

16. No current or recent (within 3 months of study drug administration) gastrointestinal
disease such as chronic or intermittent diarrhea, or disorders that increase the risk of
diarrhea, such as inflammatory bowel disease. Non-chronic conditions (e.g., infectious
diarrhea) that are completely resolved for at least 2 weeks prior to starting study
treatment is allowed.

17. For female patients of childbearing potential and male patients with partners of
childbearing potential, agreement (by patient and/or partner) to use a highly effective
form of contraception (e.g., surgical sterilization, a reliable barrier method, birth
control pills, or contraceptive hormone implants) and to continue its use for 6 months
after the last dose of study drugs.

18. Women of childbearing potential must have a negative serum pregnancy test (ß-hCG)
within 72 hours prior to first study drug administration.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Inability to comply with study and follow-up procedures (including, but not limited
to: geographical or administrative reasons, and planned vacation absences for more
than 7 consecutive days during the study).

2. Women who are pregnant or lactating.

3. Colorectal cancer patients going on to receive 1st line therapy for metastatic
disease.

4. Treatment with chemotherapy, immunotherapy, biologic therapy, or radiation therapy as
cancer therapy within 4 weeks before initiation of study treatment. Six weeks should
have elapsed if prior chemotherapy treatment included nitrosoureas or mitomycin C.

5. Treatment with any other investigational agent or participation in another clinical
trial with therapeutic intent within 28 days prior to Day 1 of Cycle 1.

6. Patients who have received antibody-based therapies within 28 days or 5 half-lives of
the agent, whichever is longer.

7. Major surgery, other than diagnostic surgery, within 6 weeks before first study drug
administration.

8. Clinically detectable (by physical exam) third-space fluid collections (e.g., ascites
or pleural effusion) that cannot be controlled by drainage or other procedures prior
to study entry.

9. Any uncontrolled medical or psychiatric risk factors which would contraindicate the
use or impair the ability of the patient to provide informed consent, receive protocol
therapy or may impose excessive risk to the patient.

10. Central nervous system (CNS) metastases, unless previously treated and well-controlled
for at least 3 months (defined as clinically stable, no edema, no steroids and stable
in 2 scans at least 4 weeks apart). Patients who display signs or symptoms of CNS
metastases or should be imaged with CT or magnetic resonance imaging (MRI) of the
head. Should metastases, including meningeal deposits be detected, these patients will
not be treated with BNC101.

11. Current use of medications that may have the potential of QTc prolongation (refer to
Appendix 1). If the need for use of these medications arises during the study, a
discussion with and approval by the sponsor would be required.

12. History of allergy or hypersensitivity to Chinese Hamster Ovary cell products, any
compound of the BNC101 formulation, or any of the chemotherapy agents to be used in
this study.

13. Active uncontrolled bacterial, viral, or fungal infection, requiring systemic therapy.

14. Patient has known infection with human immunodeficiency virus (HIV), Hepatitis B or
Hepatitis C, alcoholic or other hepatitis, or cirrhosis.

15. Inability to be venipunctured and/or tolerate venous access.

16. Second malignancies within 5 years prior to enrolment, except for those with a
negligible risk of metastasis or death, such as adequately treated carcinoma in situ
of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated
surgically with curative intent, ductal carcinoma in situ treated surgically with
curative intent.

17. Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory
drugs, inhaled corticosteroids, or the equivalent of > 10 mg/day prednisone.

18. Seizure disease requiring current anticonvulsant treatment.

19. History of inflammatory bowel disease (active or past) or active peptic ulcer disease.

20. History of chronic leukemias (e.g., chronic lymphocytic leukemia).

21. History of previous, whole abdomen radiation therapy (or total pelvic radiation
therapy in rectal cancer patients) or more than Grade 1 residual toxicity from
previous radiation therapy. NOTE: Patients with previous standard, routine
abdomino-pelvic radiotherapy are eligible and not encompassed by this criterion, which
only applies to whole abdomen or total pelvic radiotherapy.

22. Patients with high cardiovascular risk, including, but not limited to coronary
stenting in the previous 3 months or myocardial infarction in the past year [Patients
with New York Heart Association (NYHA) class I classification are acceptable].

23. Congenital or acquired long QT syndrome.

24. QTc prolongation defined as a QTc interval greater than or equal to 450 msec at
baseline; interval determination will be based on a mean value obtained from 3
baseline ECGs obtained at least 5 minutes apart.

25. Patients with history of interstitial lung disease, history of slowly progressive
dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis,
pulmonary hypersensitivity pneumonitis or multiple allergies.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2018
Sample size
Target
Accrual to date
Final
22
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 0 0
Monash Health - Clayton
Recruitment hospital [3] 0 0
Austin Health - Heidelberg
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3050 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bionomics Limited
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
CPR Pharma Services Pty Ltd, Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine the maximum tolerated dose (which will be the dose
recommended for a Phase 2 study), safety, tolerability and pharmacokinetic profile (study of
movement of the drug within the body, including absorption and distribution) of the study
drug, BNC101 when administered intravenously as a single agent or in combination with
chemotherapy in patients with metastatic colorectal cancer who have failed at least 1 or 2
lines of chemotherapy.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02726334
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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/NCT02726334