Ignite Creation Date:
2024-05-06 @ 12:05 PM
Last Modification Date:
2024-10-26 @ 12:54 PM
Study NCT ID:
NCT03673787
Status:
UNKNOWN
Last Update Posted:
2022-04-08
First Post:
2018-09-10
Brief Title:
A Trial of Ipatasertib in Combination With Atezolizumab
Sponsor:
Institute of Cancer Research United Kingdom
Organization:
Institute of Cancer Research United Kingdom
Study Overview
Official Title:
Ice-CAP A Phase I Trial of Ipatasertib in Combination With Atezolizumab in Patients With Advanced Solid Tumours With PI3K Pathway Hyperactivation
Status:
UNKNOWN
Status Verified Date:
2022-03
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IceCAP
Brief Summary:
This is a single centre proof-of-concept phase I trial of atezolizumab in combination with ipatasertib There are two parts to this study the dose escalation phase Part A and the dose expansion phase Part B Part A will determine the maximum tolerated dose MTD and recommended Phase II dose RP2D This will be followed by the Part B dose expansion phase to further characterise the safety and tolerability and to assess the pharmacodynamic activity of the combination
Detailed Description:
This is a Phase 1 trial of atezolizumab in combination with ipatasertib There are two parts to this study Part A dose escalation and Part B dose expansion
Part A
The investigators will investigate the combination of a fixed dose of atezolizumab 1200mg in combination with escalating doses of ipatasertib in patients with advanced solid tumours Cohort A1 and patients with resectable glioblastoma multiforme GBM Cohort A2
Cohort A1 advanced solid tumours
There will be an ipatasertib run-in phase of 14 days of continuous oral dosing with paired pre and post-treatment blood and tissue samples Combinations dosing will commence on Cycle 1 Day 1 with the atezolizumab infusion Cycle 1 will therefore be 35 days Only patients with advanced solid tumours recruited into Cohort A1 will be included in dose escalation decisions and determination of the MTD and recommended Phase 2 dose RP2D for part B
Cohort A2 potentially resectable GBMs
There will be an ipatasertib run-in phase of at least 14 days and up to 21 days followed by surgical resection of the patients tumour 5 day window for surgery Ipatasertib dosing will be stopped 48 hours prior to surgery and combination dosing on Cycle1Day1 C1D1 will commence after recovery Accrual to Cohort A2 will run in parallel Cohort A1 without formal dose escalations and patients in Cohort A2 will not be included in dose escalation decisions for Cohort A1
Recruitment to Part A is complete
Part B
Patients will be enrolled into the expansion phase Part B to further characterize the tolerability of the RP2D established in Cohort A1 of the combination in specific subgroups of patients Part B of the study will have a pre-screening component for patients with solid tumours Cohorts B1 and B2 to allow for enrichment for these specific subgroups of patients
Part B of the study will have three cohorts
Cohort B1 patients with solid tumours with hyperactivation of PI3K pathway as determined by pathogenic mutations identified by next generation sequencing NGS eg known activating mutations in PIK3CA AKT1 AKT2 or PTEN loss assessed by immunohistochemistry IHC n12
Cohort B2 patients with castrate-resistant prostate cancer with PTEN loss as assessed by IHC n12
Cohort B3 patients with glioblastoma n12 of which at least three n3 patients will have potentially resectable recurrent glioblastomas Recruitment to cohort B3 is complete
Cohort B4 patients with melanoma post progression on immune-checkpoint inhibitors n12
Cohort B5 patients with other tumour types refractory to immune checkpoint inhibitors where immune checkpoint inhibitors are licensed eg bladder cancer head and neck SCC NSCLC n12
Cohort B6 patients with gynaecological cancers including ovarian cancer cervical cancer endometrial cancer n12
Approximately 12 patients with solid tumours and 3 patients with glioblastoma will be entered into Part A of this trial and a further 72 patients will be enrolled into part B of the trial for an expected maximum of 87 patients on the study If the MTD is reached in Part A with less than 15 patients enrolled the investigators may enrol further patients at the R2PD in Part A to a maximum of 15 patients to include sufficient numbers of patients for the proof-of-concept translational studies Additional subjects may be enrolled in a given cohort to ensure that the required number of evaluable subjects in each cohort is achieved
Part A
The investigators will investigate the combination of a fixed dose of atezolizumab 1200mg in combination with escalating doses of ipatasertib in patients with advanced solid tumours Cohort A1 and patients with resectable glioblastoma multiforme GBM Cohort A2
Cohort A1 advanced solid tumours
There will be an ipatasertib run-in phase of 14 days of continuous oral dosing with paired pre and post-treatment blood and tissue samples Combinations dosing will commence on Cycle 1 Day 1 with the atezolizumab infusion Cycle 1 will therefore be 35 days Only patients with advanced solid tumours recruited into Cohort A1 will be included in dose escalation decisions and determination of the MTD and recommended Phase 2 dose RP2D for part B
Cohort A2 potentially resectable GBMs
There will be an ipatasertib run-in phase of at least 14 days and up to 21 days followed by surgical resection of the patients tumour 5 day window for surgery Ipatasertib dosing will be stopped 48 hours prior to surgery and combination dosing on Cycle1Day1 C1D1 will commence after recovery Accrual to Cohort A2 will run in parallel Cohort A1 without formal dose escalations and patients in Cohort A2 will not be included in dose escalation decisions for Cohort A1
Recruitment to Part A is complete
Part B
Patients will be enrolled into the expansion phase Part B to further characterize the tolerability of the RP2D established in Cohort A1 of the combination in specific subgroups of patients Part B of the study will have a pre-screening component for patients with solid tumours Cohorts B1 and B2 to allow for enrichment for these specific subgroups of patients
Part B of the study will have three cohorts
Cohort B1 patients with solid tumours with hyperactivation of PI3K pathway as determined by pathogenic mutations identified by next generation sequencing NGS eg known activating mutations in PIK3CA AKT1 AKT2 or PTEN loss assessed by immunohistochemistry IHC n12
Cohort B2 patients with castrate-resistant prostate cancer with PTEN loss as assessed by IHC n12
Cohort B3 patients with glioblastoma n12 of which at least three n3 patients will have potentially resectable recurrent glioblastomas Recruitment to cohort B3 is complete
Cohort B4 patients with melanoma post progression on immune-checkpoint inhibitors n12
Cohort B5 patients with other tumour types refractory to immune checkpoint inhibitors where immune checkpoint inhibitors are licensed eg bladder cancer head and neck SCC NSCLC n12
Cohort B6 patients with gynaecological cancers including ovarian cancer cervical cancer endometrial cancer n12
Approximately 12 patients with solid tumours and 3 patients with glioblastoma will be entered into Part A of this trial and a further 72 patients will be enrolled into part B of the trial for an expected maximum of 87 patients on the study If the MTD is reached in Part A with less than 15 patients enrolled the investigators may enrol further patients at the R2PD in Part A to a maximum of 15 patients to include sufficient numbers of patients for the proof-of-concept translational studies Additional subjects may be enrolled in a given cohort to ensure that the required number of evaluable subjects in each cohort is achieved
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
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