Colorectal CancerPhase 1NCT02726334
A Phase I, Dose Escalation Study of BNC101 in Patients With Metastatic Colorectal Cancer.
A Phase 1 study testing BNC101 Solution for Infusion and BNC101 in combination with FOLFIRI in people with Colorectal Cancer, run by Bionomics Limited at 4 sites in Australia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- BNC101 Solution for Infusion and BNC101 in combination with FOLFIRI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 4 sitesAustralia
- Study dates
- Mar 2016to Feb 2018
- Phase
- Phase 1
- 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
- Signed written Informed Consent
- Age > 18 years
- Eastern Cooperative Oncology Group (ECOG) score 0 - 1.
- 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.
- 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.
- All AEs of any prior chemotherapy, surgery, or radiotherapy, must have resolved to Grade ≤ 1.
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- Measurable or evaluable disease per RECIST version 1.1.
- No known brain metastases (see also exclusion criterion No. 10).
- Life expectancy of at least > 12 weeks.
- Normal organ and marrow function:
- Absolute neutrophil count (ANC) > 1,500/mL without growth factor support in the past 14 days prior to enrolment
- Platelets > 100,000/mL without transfusions in the past 14 days prior to enrolment
- Hemoglobin > 9.0 g/dL - Patients may be transfused or receive erythropoietic treatment to meet this criterion
- Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (< 2 x ULN for subjects with Gilbert's syndrome)
- Serum albumin ≥ 3 g/dL.
- 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).
- Alkaline phosphatase (AlkPhos) > 2.5 x ULN, except in patients with documented liver or bone metastases, where it can be < 5 x ULN.
- For patients receiving biopsies, prothrombin time (PT) and activated partial thromboplastin time (APTT)/international normalized ratio (INR) within normal limits (± 15%)..
- 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 (β-hCG) within 72 hours prior to first study drug administration.
Who cannot join
- 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).
- Women who are pregnant or lactating.
- Colorectal cancer patients going on to receive 1st line therapy for metastatic disease.
- 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.
- 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.
- Patients who have received antibody-based therapies within 28 days or 5 half-lives of the agent, whichever is longer.
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- Major surgery, other than diagnostic surgery, within 6 weeks before first study drug administration.
- 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.
- 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.
- 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.
- 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.
- 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.
- Active uncontrolled bacterial, viral, or fungal infection, requiring systemic therapy.
- Patient has known infection with human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C, alcoholic or other hepatitis, or cirrhosis.
- Inability to be venipunctured and/or tolerate venous access.
- 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.
- Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs, inhaled corticosteroids, or the equivalent of > 10 mg/day prednisone.
- Seizure disease requiring current anticonvulsant treatment.
- History of inflammatory bowel disease (active or past) or active peptic ulcer disease.
- History of chronic leukemias (e.g., chronic lymphocytic leukemia).
- 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.
- 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].
- Congenital or acquired long QT syndrome.
- 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.
- 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.
Trial locations and contacts
4 sites in 1 country.
Australia4 sites
Flinders Medical Centre
Bedford Park, South Australia, 5042
Monash Health
Clayton, Victoria, 3168
Austin Health
Heidelberg, Victoria, 3084
Royal Melbourne Hospital
Melbourne, Victoria, 3050
About this study
Official title: A Phase I, Dose Escalation Study of BNC101 (Anti-LGR5 Humanized Monoclonal Antibody) in Patients With Metastatic Colorectal Cancer.
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.
- Conditions
- Colorectal Cancer
- Being tested
- BNC101 Solution for Infusion, BNC101 in combination with FOLFIRI
- Keywords
- Metastatic
- Medical subject headings
- Colorectal Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BNC101 Solution for InfusionDrug
Also called BNC101
Administration: Administered via IV infusion once a week over 60 minutes (1 hour).
BNC101 in combination with FOLFIRIDrug
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| Group/Stream 1 - Monotherapy | Experimental | 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. Receives: Drug: BNC101 Solution for Infusion |
| Group/Stream 2 - Combination Chemo | Experimental | 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. Receives: Drug: BNC101 in combination with FOLFIRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
To determine the maximum tolerated dose (MTD) of BNC101, both as single agent and in combination chemotherapy in metastatic colorectal cancer patients.
Measured: DLT period of 28 days per dose level
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2016 (estimated)
- Study startMar 2016
- Primary completionDec 2017
- Study completionFeb 2018
Why it stopped: Monotherapy arm completed. Combination arm did not proceed (sponsor decision).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bionomics Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- CPR Pharma Services Pty Ltd, Australia
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02726334
- Sponsor's protocol ID
- BNC101. 001
- Status last verified
- Jan 2019
- First submitted
- 28 Mar 2016
- Last updated
- 16 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Dose Escalation Study of BNC101 (Anti-LGR5 Humanized Monoclonal Antibody) in Patients With Metastatic Colorectal Cancer.
- ClinicalTrials.gov ID
- NCT02726334
- Acronym / sponsor ID
- BNC101. 001
- Conditions
- Colorectal Cancer
- Keywords
- Metastatic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Monotherapy arm completed. Combination arm did not proceed (sponsor decision).
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Bionomics LimitedIndustry (pharma, biotech, devices)
- Collaborators
- CPR Pharma Services Pty Ltd, Australia
- Study start
- Mar 2016 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 1 Apr 2016 (estimated)
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group/Stream 1 - Monotherapy | Experimental | Drug: BNC101 Solution for InfusionPatient 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. |
| Group/Stream 2 - Combination Chemo | Experimental | Drug: BNC101 in combination with FOLFIRIPatient 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Signed written Informed Consent
- Age > 18 years
- Eastern Cooperative Oncology Group (ECOG) score 0 - 1.
- 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.
- 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.
Key exclusion criteria (25 listed)
- 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).
- Women who are pregnant or lactating.
- Colorectal cancer patients going on to receive 1st line therapy for metastatic disease.
- 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.
- 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.
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 |
|---|---|---|
| BNC101 Solution for InfusionAlso: BNC101Administration: Administered via IV infusion once a week over 60 minutes (1 hour). | Drug | Group/Stream 1 - Monotherapy |
| BNC101 in combination with FOLFIRIAlso: FOLFIRIBNC101 - 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. | Drug | Group/Stream 2 - Combination Chemo |
Primary outcome
Maximum Tolerated Dose
Time frame: DLT period of 28 days per dose level
To determine the maximum tolerated dose (MTD) of BNC101, both as single agent and in combination chemotherapy in metastatic colorectal cancer patients.
Results and safety
The study was stopped early (reason given: Monotherapy arm completed. Combination arm did not proceed (sponsor decision).). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2019.
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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.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BNC101 Solution for Infusion and BNC101 in combination with FOLFIRI in people with Colorectal Cancer, run by Bionomics Limited at 4 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 26 inclusion and 25 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: stopped early, as of the sponsor's last update on 16 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was stopped early (reason given: Monotherapy arm completed. Combination arm did not proceed (sponsor decision).). Results are not available in the source record.
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?
Maximum Tolerated Dose (time frame: DLT period of 28 days per dose level). 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 16 Jan 2019.