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Trial registered on ANZCTR


Registration number
ACTRN12618000838213
Ethics application status
Approved
Date submitted
11/05/2018
Date registered
18/05/2018
Date last updated
24/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase 1 clinical trial of BIL06v/Alhydrogel to evaluate the safety, tolerability, immunogenicity and anti-tumour activity and to determine the most effective dose of BIL06v/Alhydrogel to treat patients with advanced forms of solid cancers
Scientific title
A Phase 1 Study to Evaluate the Safety, Tolerability, Immunogenicity and Anti-Tumour Activity of BIL06v/Alhydrogel in Patients with Advanced Solid Tumours
Secondary ID [1] 291740 0
Nil known
Universal Trial Number (UTN)
U1111-1196-0106
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Cancers 302948 0
Condition category
Condition code
Cancer 302416 302416 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an open label Phase 1 study of BIL06v/Alhydrogel® administered as a subcutaneous (SC) injection as a single agent every 2 weeks for 12 doses. Two doses, 1000ug and 1500ug, will be explored. An initial set of 10 patients will be enrolled in the 1000ug dose cohort; if there are no safety concerns, another 10 patients are planned for the 1500ug dose cohort. Throughout each dose cohort, the members of the Safety Review Committee (SRC) will review the safety data at such times and such frequency as determined clinically appropriate by the SRC.

As an added safety measure, the first dose in all patients will be 500µg. If there is no Dose Limiting Toxicity (DLT) in 14 days following the first dose in each patient, dosing will continue at the assigned dose level with no subsequent intrapatient dose-escalation. After a patient is enrolled, no specific window of time is needed to pass before the next patient is allowed to enrol in that cohort.

If less than 8 patients, in each cohort, are treated for 5 cycles (10 doses) or more, then those patients without suitable BIL06v/Alhydrogel® exposure will be replaced. A suitable number of patients will be enrolled to ensure reasonable confidence that at least 8 patients per cohort will be treated for 5 cycles (10 doses) or more. A maximum of 30 patients will be recruited for this study irrespective of the number of patients who drop out.

A cycle is a period of 28 days. BIL06v/Alhydrogel® will be administered by the Principal Investigator or their designated study staff. The trial will be conducted in accordance with the trial protocol and any deviations from the trial protocol must be adequately documented and reported.
Intervention code [1] 297848 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 301823 0
To evaluate the safety of BIL06v/Alhydrogel® in patients with advanced solid tumours. The members of the Safety Review Committee (SRC) will review the safety data including, without limitation, biochemistry, haematology, coagulation panel and urinalysis, at such times and such frequency as determined clinically appropriate by the SRC.
Timepoint [1] 301823 0
Safety data will be collected at baseline screening, fortnightly for 12 fortnights, monthly thereafter until such time as the participant is withdrawn from the study (including without limitation, due to adverse events, disease progression, death, protocol violations, withdrawal of consent or voluntary withdrawal from participation) and at the end of study visit.
Primary outcome [2] 305884 0
To evaluate the serological immunogenicity of BIL06v/Alhydrogel® in patients with advanced solid tumours. The serological immunogencity will be evaluated by enzyme-linked immunosorbent assay (ELISA) at the conclusion of the study.
Timepoint [2] 305884 0
Serological immunogenicity samples will be collected fortnightly for 12 fortnights, monthly thereafter until such time as the participant is withdrawn from the study (including without limitation, due to adverse events, disease progression, death, protocol violations, withdrawal of consent or voluntary withdrawal from participation) and at the end of study visit.
Secondary outcome [1] 333968 0
To evaluate the Dose Limiting Toxicity (DLT) of BIL06v/Alhydrogel®. The members of the Safety Review Committee (SRC) will review the appropriate data including, without limitation, biochemistry, haematology, coagulation panel and urinalysis, at such times and such frequency as determined clinically appropriate.
Timepoint [1] 333968 0
Safety data collected at baseline screening, fortnightly for 12 fortnights, monthly thereafter until such time as the participant is withdrawn from the study (including without limitation, due to adverse events, disease progression, death, protocol violations, withdrawal of consent or voluntary withdrawal from participation) and at the end of study visit will be used to evaluate DLT.
Secondary outcome [2] 333969 0
To evaluate the Maximum Tolerated Dose (MTD) or recommended Phase 2 dose (RP2D) of BIL06v/Alhydrogel®, in the event that MTD is not met. The MTD or RP2D will be determined by the Sponsor and Investigator(s) based on the safety data, including, without limitation, biochemistry, haematology, coagulation panel and urinalysis, immunogenicity, including without limitation from enzyme-linked immunosorbent assay (ELISA), and efficacy data, including without limitation from computed tomography scans, from the 2 cohorts.
Timepoint [2] 333969 0
Safety data collected at at baseline screening, fortnightly for 12 fortnights, monthly thereafter and at the end of study visit, immunogenicity data collected fortnightly for 12 fortnights, monthly thereafter until such time as the participant is withdrawn from the study (including without limitation, due to adverse events, disease progression, death, protocol violations, withdrawal of consent or voluntary withdrawal from participation) and at the end of study visit, and efficacy data collected at baseline screening and every 12 weeks thereafter will be used to evaluate MTD and RP2D.

Secondary outcome [3] 346846 0
To evaluate the preliminary anti-tumour activity of BIL06v/Alhydrogel® as measured by disease control rate (stable disease [SD] + partial response [PR] + complete response [CR] by computed tomography scan at 12 weeks) according to modified Response Evaluation Criteria in Solid Tumours (mRECIST).
Timepoint [3] 346846 0
Computed tomography scans will be conducted at screening and every 12 weeks thereafter until such time as the participant is withdrawn from the study (including without limitation, due to adverse events, disease progression, death, protocol violations, withdrawal of consent or voluntary withdrawal from participation).
Secondary outcome [4] 346847 0
To evaluate the preliminary anti-tumour activity of BIL06v/Alhydrogel® as measured by progression-free survival (PFS) by computed tomography scan according to modified Response Evaluation Criteria in Solid Tumours (mRECIST).
Timepoint [4] 346847 0
Computed tomography scans will be conducted at screening and every 12 weeks thereafter until such time as the participant is withdrawn from the study (including without limitation, due to adverse events, disease progression, death, protocol violations, withdrawal of consent or voluntary withdrawal from participation).

Eligibility
Key inclusion criteria
1. Men and women who are >= 18 years old;
2. Provide written, informed consent to participate in the study and follow the study procedures;
3. Patients with locally advanced or metastatic solid tumour cancers refractory to at least one course of prior standard systemic therapy, or who refuse or want to delay standard therapy, or for whom no effective standard therapy is available;
4. Cytological or pathological evidence of cancer;
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Patients who refuse or want to delay standard therapy must have an ECOG performance status of 0;
6. Life expectancy >= 12 weeks;
7. Women of child bearing potential must agree and commit to the use of a highly effective method of contraception, as determined to be acceptable by the investigator, from the time of informed consent until 90 days after the last dose of the investigational product. Men must agree and commit to use a barrier method of contraception while on treatment and for 90 days after the last dose of the investigational product.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Inadequate haematologic or organ function;
2. Any anti-cancer therapy, including chemotherapy, hormonal therapy, biologic therapy, targeted therapy, anti-angiogenic therapy, surgery or radiotherapy within 14 days prior to initiation of study treatment, with certain exceptions;
3. Active corticosteriod therapy (e.g. prednisolone doses >10mg daily or dexamethasone doses >2mg daily or equivalents) within 14 days of initiation of study treatment;
4. ECOG performance status 2-4.
5. Allergies to any component of the BIL06v/Alhydrogel vaccine;
6. Uncontrolled active infection;
7. Known human immunodefciency virus (HIV) infection. HIV testing is not required at screening;
8. Pregnant or lactating women;
9. Active symptomatic or uncontrolled brain metastasis. Patients with treated or asymptomatic brain metastases before 14 days of study initiation are eligible;
10. Inability to comply with study and follow-up procedures.

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
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7869 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [2] 11990 0
Sydney Southwest Private Hospital - Liverpool
Recruitment postcode(s) [1] 15815 0
2076 - Wahroonga
Recruitment postcode(s) [2] 24137 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 296235 0
Commercial sector/Industry
Name [1] 296235 0
Biosceptre (Aust) Pty Limited
Address [1] 296235 0
11 Julius Avenue, North Ryde, NSW 2113
Country [1] 296235 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Biosceptre (Aust) Pty Limited
Address
11 Julius Avenue, North Ryde, NSW 2113
Country
Australia
Secondary sponsor category [1] 295154 0
None
Name [1] 295154 0
Address [1] 295154 0
Country [1] 295154 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297474 0
Bellberry Limited
Ethics committee address [1] 297474 0
129 Glen Osmond Road
Eastwood, South Australia, 5063
Ethics committee country [1] 297474 0
Australia
Date submitted for ethics approval [1] 297474 0
Approval date [1] 297474 0
21/02/2018
Ethics approval number [1] 297474 0
2017-12-915
Ethics committee name [2] 301535 0
Bellberry Human Research Ethics Committee D [EC00444]
Ethics committee address [2] 301535 0
129 Glen Osmond Road
Eastwood, SA 5063
Ethics committee country [2] 301535 0
Australia
Date submitted for ethics approval [2] 301535 0
Approval date [2] 301535 0
07/06/2018
Ethics approval number [2] 301535 0
2017-12-915-AA

Summary
Brief summary
Purpose
The purpose of this study is to evaluate the safety, tolerability, immunogenicity and anti-tumour activity of BIL06v/Alhydrogel in patients with advanced solid tumours.

Who is it for?
Adults who have locally advanced or metastatic solid tumours.

Study details
This is a two-cohort study which means approximately 10-15 participants assigned to 1 dose of BIL06v/Alhydrogel®, and a different cohort of 10-15 participants assigned to a different dose of BIL06v/Alhydrogel®. In total, approximately 20-30 participants will be enrolled in this study at 2-4 sites in Australia.

Participants will be assigned to a cohort and dose level by the study doctor. The study treatment will take place in two parts depending on the number of treatments each participant receives (see below).

Participants who are continuing to benefit from the study treatment, according to the study doctor, may continue to receive study treatment, as appropriate, for up to approximately 2 years.

Part 1
In Part 1, BIL06v/Alhydrogel® is administered every 14 days up to the 12th treatment (22 weeks) as subcutaneous injections (a short needle is used to inject the drug under the skin).

Dose Level 1: 1.0mg each dose
Dose Level 2: 1.5mg each dose

A maximum of 15 participants will be enrolled in each dose level group. Dosing at the next level will occur sequentially, after completion of enrolment of participants in the first dose cohort. Treatment will be monitored by the study doctor/s, and the medically qualified Safety Review Committee (SRC) to ensure safety is maintained. The SRC may choose to change the planned dose schedule based on results from the previous groups.

Part 2
Once a participant has received 12 injections of BIL06v/Alhydrogel®, which will occur at the end of Cycle 6, the participant will enter Part 2 of the study. In Part 2, which will start in Cycle 7, study treatments will be given at 28 day intervals. Participants will continue to receive the same dose once every 28 days until the study doctor determines participants are not benefiting from treatment or if participants are not compliant with the study protocol.

Participants will be required to attend a Screening Visit to assess their eligibility for the study up to two weeks before being given BIL06v/Alhydrogel®. Participants will need to return to the study site for a Treatment Visit (Day 1) for administration of BIL06v/Alhydrogel® and to have a number of assessments performed to check their general health. During the treatment period, participants will be required to attend the study site for BIL06v/Alhydrogel® administration every 14 days (treatment cycles 1-6) and every 28 days thereafter (cycles 7 and beyond), for ongoing safety, tolerability, immunogenicity and clinical assessments to be conducted.

Biosceptre hopes this treatment may extend overall survival for some participants.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74162 0
A/Prof Gavin Marx
Address 74162 0
Sydney Adventist Hospital
185 Fox Valley Road,
Wahroonga, NSW 2076
Country 74162 0
Australia
Phone 74162 0
+612 9480 4280
Fax 74162 0
Email 74162 0
enquiries@nhog.com.au
Contact person for public queries
Name 74163 0
Ms Nina Singh
Address 74163 0
Sydney Adventist Hospital
185 Fox Valley Road,
Wahroonga, NSW 2076
Country 74163 0
Australia
Phone 74163 0
+612 9480 6280
Fax 74163 0
Email 74163 0
nina.singh@sah.org.au
Contact person for scientific queries
Name 74164 0
A/Prof Gavin Marx
Address 74164 0
Sydney Adventist Hospital
185 Fox Valley Road,
Wahroonga, NSW 2076
Country 74164 0
Australia
Phone 74164 0
+612 9480 4280
Fax 74164 0
Email 74164 0
enquiries@nhog.com.au

No data has been provided for results reporting
Summary results
Not applicable