Ignite Creation Date:
2024-07-17 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06471673
Status:
RECRUITING
Last Update Posted:
2024-06-24
First Post:
2024-06-11
Brief Title:
A Study of BRIA-OTS Cellular Immunotherapy in Metastatic Recurrent Breast Cancer
Sponsor:
BriaCell Therapeutics Corporation
Organization:
BriaCell Therapeutics Corporation
Study Overview
Official Title:
A Study of BRIA-OTS Cellular Immunotherapy in Metastatic Recurrent Breast Cancer
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is an open-label Phase 12a study Once the safety of the BC1 cell line alone has been demonstrated in Phase 1 in Phase 2 patients will be treated with the Bria-OTS regimen see below and a clinically available check point inhibitor CPI
During the monotherapy phase of Phase 1 one patient will be treated intradermally every 2 weeks for 6 weeks 4 doses with an initial dose of the BC1 cell line If this dose is tolerated the next patient will receive an increased dose of BC1 If once again tolerated the third patient will receive a further dose increase of the BC1 Once at least 3 patients have been safely treated with the BC1 cell line with no dose-limiting toxicity DLT the combinational phase of the study will commence
Following the monotherapy phase patients will be treated with BC1 and the Bria-OTS regimen see below every 3 weeks plus a CPI at the FDA approved labelled dose and schedule There will be at least a 2-week spacing between enrollment of each of the first three subjects in the study in order to assess for any early unanticipated risks
During the Phase 1 combination and Phase 2 expansion phases all patients will be treated with BC1 cells as part of the Bria-OTS regimen which includes cyclophosphamide 300 mgm2 2-3 days prior to BC1 cell inoculation and peginterferon alpha-2a administered on the same day following BC1 cell inoculation
During the monotherapy phase of Phase 1 one patient will be treated intradermally every 2 weeks for 6 weeks 4 doses with an initial dose of the BC1 cell line If this dose is tolerated the next patient will receive an increased dose of BC1 If once again tolerated the third patient will receive a further dose increase of the BC1 Once at least 3 patients have been safely treated with the BC1 cell line with no dose-limiting toxicity DLT the combinational phase of the study will commence
Following the monotherapy phase patients will be treated with BC1 and the Bria-OTS regimen see below every 3 weeks plus a CPI at the FDA approved labelled dose and schedule There will be at least a 2-week spacing between enrollment of each of the first three subjects in the study in order to assess for any early unanticipated risks
During the Phase 1 combination and Phase 2 expansion phases all patients will be treated with BC1 cells as part of the Bria-OTS regimen which includes cyclophosphamide 300 mgm2 2-3 days prior to BC1 cell inoculation and peginterferon alpha-2a administered on the same day following BC1 cell inoculation
Detailed Description:
Open-label Phase 12a study
Once the safety of the BC1 cell line alone has been demonstrated in Phase 1 in Phase 2 patients will be treated with the Bria-OTS regimen see below and a check point inhibitor CPI
During the monotherapy phase of Phase 1 one patient will be treated intradermally every 2 weeks for 6 weeks 4 doses with an initial dose of the BC1 cell line If this dose is tolerated the next patient will receive an increased dose of BC1 cells If once again tolerated the third patient will receive a further increased dose of BC1 Once at least 3 patients have been safely treated with the BC1 cell line with no dose-limiting toxicity DLT the combinational phase of the study will commence
Following the monotherapy phase patients will be treated with BC1 and the Bria-OTS regimen see below every 3 weeks plus a CPI at the FDA approved labelled dose and schedule There will be at least a 2-week spacing between enrollment of each of the first three subjects in the study in order to assess for any early unanticipated risks
During the Phase 1 combination and Phase 2 expansion phases all patients will be treated with BC1 cells as part of the Bria-OTS regimen which includes cyclophosphamide 300 mgm2 2-3 days prior to BC1 cell inoculation and peginterferon alpha-2a administered on the same day following BC1 cell inoculation
Imaging studies will be performed at screening for baseline prior to first treatment after the completion of the monotherapy phase just before starting the combination phase and subsequently every 9 weeks for the first 6 months then q12 weeks thereafter while on treatment
Patients who develop progressive disease on imaging may remain on treatment as long as the Investigator feels they are deriving clinical benefit and there is no reasonable meaningful clinical alternative therapy available Subjects will continue to be followed for time on subsequent therapy PFS2 and survival by phone call or medical record review every 3 months for up to 2 years
Study Drug Dosage and Mode of Administration
The Part 1 monotherapy phase of Phase 1 will proceed as follows for each patient
Subject 1 Q2w for 4 doses Subject 2 Q2w for 4 doses Subject 3 Q2w for 4 doses
Initially safety will be assessed on these 3 subjects DLTs are defined as CTCAE Grade 3 or 4 adverse events that are suspected to be possibly related to study treatment
If 1 of 3 Phase 1 subjects experience a DLT that dose cohort will be expanded to another 3 patients before the combinational phase begins If none of the patients in the expanded cohort experience a DLT DLT rate of 14 the study will move into Bria-OTS and CPI combination The dose for the combination will be either the highest dose at which no DLT is observed among the first 3 patients or the 3 patient expanded cohort dose level In Phase 1 DLTs for determining the combinational BC1 dose will be observed until the first scheduled assessment If the Phase 1 DLT rate is 24 an additional 3 patients will be dosed using the next lower dose level or 10 million cells whichever is higher If none of the 3 subjects experience dose-limiting toxicities DLTs that determined BC1 MTD dose will be included in the Part 2 combinational phase of Phase 1 along with a CPI If a tolerated dose for BC1 cell line cannot be identified further investigation will be paused the data reviewed and may resume at a lower dose only with protocol amendment and IRB approval
Following the Phase 1 Part 1 monotherapy phase 3 patients will be treated every 3 weeks with the Bria-OTS regimen with a CPI in the Part 2 combination phase The Bria-OTS regimen consists of cyclophosphamide 300 mgm2 2-3 days prior to BC1 cell line inoculation On the same day as the cell inoculation subjects will receive peginterferon alpha-2a Subjects will also receive the CPI on the same day of the cell inoculation according to approved dosing
Once 3 patients have been safely treated with the Bria-OTS regimen and CPI for 2 cycles Phase 2 will enroll an expansion cohort consisting of up to an additional 9 subjects for a total of 12 treated with the Bria-OTS regimen and CPI
Once the safety of the BC1 cell line alone has been demonstrated in Phase 1 in Phase 2 patients will be treated with the Bria-OTS regimen see below and a check point inhibitor CPI
During the monotherapy phase of Phase 1 one patient will be treated intradermally every 2 weeks for 6 weeks 4 doses with an initial dose of the BC1 cell line If this dose is tolerated the next patient will receive an increased dose of BC1 cells If once again tolerated the third patient will receive a further increased dose of BC1 Once at least 3 patients have been safely treated with the BC1 cell line with no dose-limiting toxicity DLT the combinational phase of the study will commence
Following the monotherapy phase patients will be treated with BC1 and the Bria-OTS regimen see below every 3 weeks plus a CPI at the FDA approved labelled dose and schedule There will be at least a 2-week spacing between enrollment of each of the first three subjects in the study in order to assess for any early unanticipated risks
During the Phase 1 combination and Phase 2 expansion phases all patients will be treated with BC1 cells as part of the Bria-OTS regimen which includes cyclophosphamide 300 mgm2 2-3 days prior to BC1 cell inoculation and peginterferon alpha-2a administered on the same day following BC1 cell inoculation
Imaging studies will be performed at screening for baseline prior to first treatment after the completion of the monotherapy phase just before starting the combination phase and subsequently every 9 weeks for the first 6 months then q12 weeks thereafter while on treatment
Patients who develop progressive disease on imaging may remain on treatment as long as the Investigator feels they are deriving clinical benefit and there is no reasonable meaningful clinical alternative therapy available Subjects will continue to be followed for time on subsequent therapy PFS2 and survival by phone call or medical record review every 3 months for up to 2 years
Study Drug Dosage and Mode of Administration
The Part 1 monotherapy phase of Phase 1 will proceed as follows for each patient
Subject 1 Q2w for 4 doses Subject 2 Q2w for 4 doses Subject 3 Q2w for 4 doses
Initially safety will be assessed on these 3 subjects DLTs are defined as CTCAE Grade 3 or 4 adverse events that are suspected to be possibly related to study treatment
If 1 of 3 Phase 1 subjects experience a DLT that dose cohort will be expanded to another 3 patients before the combinational phase begins If none of the patients in the expanded cohort experience a DLT DLT rate of 14 the study will move into Bria-OTS and CPI combination The dose for the combination will be either the highest dose at which no DLT is observed among the first 3 patients or the 3 patient expanded cohort dose level In Phase 1 DLTs for determining the combinational BC1 dose will be observed until the first scheduled assessment If the Phase 1 DLT rate is 24 an additional 3 patients will be dosed using the next lower dose level or 10 million cells whichever is higher If none of the 3 subjects experience dose-limiting toxicities DLTs that determined BC1 MTD dose will be included in the Part 2 combinational phase of Phase 1 along with a CPI If a tolerated dose for BC1 cell line cannot be identified further investigation will be paused the data reviewed and may resume at a lower dose only with protocol amendment and IRB approval
Following the Phase 1 Part 1 monotherapy phase 3 patients will be treated every 3 weeks with the Bria-OTS regimen with a CPI in the Part 2 combination phase The Bria-OTS regimen consists of cyclophosphamide 300 mgm2 2-3 days prior to BC1 cell line inoculation On the same day as the cell inoculation subjects will receive peginterferon alpha-2a Subjects will also receive the CPI on the same day of the cell inoculation according to approved dosing
Once 3 patients have been safely treated with the Bria-OTS regimen and CPI for 2 cycles Phase 2 will enroll an expansion cohort consisting of up to an additional 9 subjects for a total of 12 treated with the Bria-OTS regimen and CPI
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None