ANZCTR - Registration

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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

10/12/2020

Date data sharing statement initially provided

30/08/2019

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]

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

Condition category

Condition code

Cancer

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]

Treatment: Drugs

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

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]

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]

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]

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]

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]

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]

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]

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 Response Evaluation Criteria in Solid Tumours (RECIST 1.1).

Timepoint [3]

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]

To evaluate the preliminary anti-tumour activity of BIL06v/Alhydrogel® as measured by progression-free survival (PFS) by computed tomography scan according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1).

Timepoint [4]

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

Sex

Both males and females

Can healthy volunteers participate?

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

Completed

Date of first participant enrolment

Anticipated

18/06/2018

Actual

15/08/2018

Date of last participant enrolment

Anticipated

Actual

6/08/2019

Date of last data collection

Anticipated

30/06/2020

Actual

11/05/2020

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Sydney Adventist Hospital - Wahroonga

Recruitment hospital [2]

Sydney Southwest Private Hospital - Liverpool

Recruitment postcode(s) [1]

2076 - Wahroonga

Recruitment postcode(s) [2]

2170 - Liverpool

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Biosceptre (Aust) Pty Limited

Address [1]

11 Julius Avenue, North Ryde, NSW 2113

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry Limited

Ethics committee address [1]

129 Glen Osmond Road
Eastwood, South Australia, 5063

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

21/02/2018

Ethics approval number [1]

2017-12-915

Ethics committee name [2]

Bellberry Human Research Ethics Committee D [EC00444]

Ethics committee address [2]

129 Glen Osmond Road
Eastwood, SA 5063

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

Approval date [2]

07/06/2018

Ethics approval number [2]

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

A/Prof Gavin Marx

Address

Sydney Adventist Hospital
185 Fox Valley Road,
Wahroonga, NSW 2076

Country

Australia

Phone

+612 9480 4280

Fax

enquiries@nhog.com.au

Contact person for public queries

Name

Nina Singh

Address

Sydney Adventist Hospital
185 Fox Valley Road,
Wahroonga, NSW 2076

Country

Australia

Phone

+612 9480 6280

Fax

nina.singh@sah.org.au

Contact person for scientific queries

Name

Gavin Marx

Address

Sydney Adventist Hospital
185 Fox Valley Road,
Wahroonga, NSW 2076

Country

Australia

Phone

+612 9480 4280

Fax

enquiries@nhog.com.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	P2X7 in Cancer: From Molecular Mechanisms to Therapeutics	2020	https://doi.org/10.3389/fphar.2020.00793
Dimensions AI	Various Aspects of Calcium Signaling in the Regulation of Apoptosis, Autophagy, Cell Proliferation, and Cancer	2020	https://doi.org/10.3390/ijms21218323

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically