Ignite Creation Date:
2024-05-06 @ 11:06 AM
Last Modification Date:
2024-10-26 @ 12:40 PM
Study NCT ID:
NCT03436056
Status:
TERMINATED
Last Update Posted:
2022-09-09
First Post:
2018-01-16
Brief Title:
PembRolIzuMab and Stereotactic Body Radiotherapy In Metastatic Non-small-cell lunG Cancer Patients
Sponsor:
Royal Marsden NHS Foundation Trust
Organization:
Royal Marsden NHS Foundation Trust
Study Overview
Official Title:
PembRolIzuMab and Stereotactic Body Radiotherapy In Metastatic Non-small-cell lunG Cancer Patients
Status:
TERMINATED
Status Verified Date:
2022-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
funding pulled
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PRIMING
Brief Summary:
This is a single centre non-randomised open label phase 1 trial of lung SBRT to part of a lung lesion in patients with advanced NSCLC in combination with pembrolizumab This study will recruit up to 24 patients whose lung cancer has progressed beyond one line of palliative chemotherapy and an EGFR or ALK inhibitor if an EGFR driver mutation or ALK gene rearrangement is present respectively and now requires further palliative systemic treatment
Detailed Description:
The study will be conducted in two parts an initial lung SBRT dose escalation phase Part A followed by a lung SBRT dose expansion cohort Part B The dose escalation phase is based on a 33 design such that patients will be treated in cohorts of 3-6 patients A maximum of 12 patients will be allocated to one of two doses of lung SBRT in combination with pembrolizumab to determine the MTD DLTs and RP2D If there is more than one DLT in cohort 1 this treatment combination will be deemed as being unacceptable and it would lead to termination of the study Note there is no de-escalation in cohort 1 During the dose expansion cohort 12 patients will have lung SBRT dosed at the RP2D determined during the dose escalation phase in combination with pembrolizumab to obtain additional safety and response data Maintenance pembrolizumab will continue until disease progression unacceptable toxicities the patient withdraws consent to the trial or the patient has completed 24 months of treatment A maximum of 24 patients will be treated in the study
All patients will receive pembrolizumab on cycle C 1 day D 1 in Part A and B of the study All patients will receive lung SBRT on C1D15 C1D17 and C1D19 as per lung SBRT protocol See Appendix 3 Although C1D1 can occur - 3 days C1D15 C1D17 and C1D19 must be scheduled for a Monday Wednesday and Friday respectively Patients in part A will receive lung SBRT dosed at 30 Gy in 3 in cohort 1 or 54 Gy in 3 in cohort 2 Patients in Part B will receive the RP2D of lung SBRT determined in Part A All patients in Part A and Part B will receive pembrolizumab dosed at 200 mg every 3 weeks until disease progression unacceptable toxicities the patient withdraws consent from the trial or the patient has completed 24 months of treatment
In the dose escalation phase a minimum of 3 patients will be required per dose level being assessed A minimum gap of 1 week will be left between the treatment of the first and the second and between the second and the third patients with the combination of pembrolizumab and lung SBRT to mitigate against multiple patients suffering from acute toxicity The DLT period for this study is 12 weeks from the last dose of lung SBRT ie at C6D1 The dose escalation will be considered by the Safety Review Committee SRC once the 3rd or 6th patient in the cohort has completed the DLT period If no DLT is observed at a dose level then lung SBRT will be dose escalated to the next dosing level see Table 1 If 1 out of 3 patients experience a DLT then the cohort will be expanded to 6 patients If 1 in 6 patients experience a DLT then the dose will be escalated to the next dosing level However if 2 in 6 patients experience a DLT then the maximum administered dose MAD will have been reached and the RP2D will be the previous dosing level that will be used for the dose expansion cohorts If the MAD is seen at dose level 1 then the study will be terminated While waiting for 3 or 6 patients to complete the DLT period no additional patients will be recruited Further patients can only be recruited after the SRC has reviewed the toxicity data for the cohort and taken a decision to dose escalate to the next cohort or expand the current cohort to 6 patients
Once the MTD has been determined the trial enters the dose expansion phase unless the MTD is dose level 1 Here 12 patients will be treated with the RP2D of SBRT combined with pembrolizumab
If there is ongoing clinical benefit at 24 months the CIPI will need to discuss with the sponsor and MSD on a case by case basis for the continuation of pembrolizumab
All patients will receive pembrolizumab on cycle C 1 day D 1 in Part A and B of the study All patients will receive lung SBRT on C1D15 C1D17 and C1D19 as per lung SBRT protocol See Appendix 3 Although C1D1 can occur - 3 days C1D15 C1D17 and C1D19 must be scheduled for a Monday Wednesday and Friday respectively Patients in part A will receive lung SBRT dosed at 30 Gy in 3 in cohort 1 or 54 Gy in 3 in cohort 2 Patients in Part B will receive the RP2D of lung SBRT determined in Part A All patients in Part A and Part B will receive pembrolizumab dosed at 200 mg every 3 weeks until disease progression unacceptable toxicities the patient withdraws consent from the trial or the patient has completed 24 months of treatment
In the dose escalation phase a minimum of 3 patients will be required per dose level being assessed A minimum gap of 1 week will be left between the treatment of the first and the second and between the second and the third patients with the combination of pembrolizumab and lung SBRT to mitigate against multiple patients suffering from acute toxicity The DLT period for this study is 12 weeks from the last dose of lung SBRT ie at C6D1 The dose escalation will be considered by the Safety Review Committee SRC once the 3rd or 6th patient in the cohort has completed the DLT period If no DLT is observed at a dose level then lung SBRT will be dose escalated to the next dosing level see Table 1 If 1 out of 3 patients experience a DLT then the cohort will be expanded to 6 patients If 1 in 6 patients experience a DLT then the dose will be escalated to the next dosing level However if 2 in 6 patients experience a DLT then the maximum administered dose MAD will have been reached and the RP2D will be the previous dosing level that will be used for the dose expansion cohorts If the MAD is seen at dose level 1 then the study will be terminated While waiting for 3 or 6 patients to complete the DLT period no additional patients will be recruited Further patients can only be recruited after the SRC has reviewed the toxicity data for the cohort and taken a decision to dose escalate to the next cohort or expand the current cohort to 6 patients
Once the MTD has been determined the trial enters the dose expansion phase unless the MTD is dose level 1 Here 12 patients will be treated with the RP2D of SBRT combined with pembrolizumab
If there is ongoing clinical benefit at 24 months the CIPI will need to discuss with the sponsor and MSD on a case by case basis for the continuation of pembrolizumab
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?:
False
Is an FDA AA801 Violation?:
None