Ignite Creation Date:
2024-05-06 @ 11:14 AM
Last Modification Date:
2024-10-26 @ 12:42 PM
Study NCT ID:
NCT03462212
Status:
RECRUITING
Last Update Posted:
2021-08-27
First Post:
2018-02-14
Brief Title:
Carboplatin-Paclitaxel-Bevacizumab vs Carbo-Pacli-Beva-Rucaparib vs Carbo-Pacli-Ruca Selected According to HRD Status in Patients With Advanced Ovarian Primary Peritoneal and Fallopian Tube Cancer Preceded by a Phase I Dose Escalation Study on Ruca-Beva Combination
Sponsor:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Organization:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study Overview
Official Title:
A Randomized Molecular Driven Phase II Trial of Carboplatin-Paclitaxel-Bevacizumab vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib vs Carboplatin-Paclitaxel-Rucaparib Selected According to HRD Status in Patients With Advanced Stage III B-C-IV Ovarian Primary Peritoneal and Fallopian Tube Cancer Preceded by a Phase I Dose Escalation Study on Rucaparib-Bevacizumab Combination
Status:
RECRUITING
Status Verified Date:
2021-08
Last Known Status:
None
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:
MITO25
Brief Summary:
This trial is a randomized open-label Phase I-2 multi-center study designed to evaluate the effect of Carboplatin-Paclitaxel-Bevacizumab in combination and maintenance vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib Rucaparib only in maintenance vs Carboplatin-Paclitaxel-Rucaparib Rucaparib only in maintenance on progression-free survival in patients with advanced high grade ovarian cancer treated according to HRD status The trial will test the hypothesis that Carboplatin-Paclitaxel-Bevacizumab-Rucaparib and the Carboplatin-Paclitaxel-Rucaparib arms will improve the progression-free survival in comparison to standard Carboplatin-Paclitaxel-Bevacizumab in HRD negative HR proficient patients and that Carboplatin-Paclitaxel-Bevacizumab-Rucaparib will improve PFS with respect to Carboplatin-Paclitaxel-Rucaparib in HRD positive patients The randomized phase of the study will be preceded by a single arm Phase I study which will be conducted only in the National Cancer Institute of Milan aiming at evaluating the MTD of the combination Rucaparib-Bevacizumab Once the MTD has been reached the randomized study will start
Detailed Description:
Phase I study design
This is a single-centre Phase I open-label dose-escalation study to evaluate the safety and tolerability of bevacizumab-rucaparib combination and determine the MTD in patients with advanced epithelial ovarian fallopian tube or primary peritoneal cancer
The dose of bevacizumab is fixed in cohort 1 2 and 3 of the study at 15mgkg q 3 weekly
The dose of rucaparib is evaluated in three cohorts 400 mg BID 500 mg BID 600 mg BID
This trial will enroll at least 3 patients in cohort 1 with dose escalation to rucaparib 500 mg from cohort 1 to 2 Cohort 2 will enroll at least 3 patients with dose escalation to rucaparib 600 mg from cohort 2 to 3
The standard 33 design will be used Patients will be enrolled in cohort of 3 patients if no DLT event will be reported among the first 3 patients a second cohort will be enrolled at the upper dose level If 1 DLT event is registered in the first cohort other 3 patients will be enrolled at the same dose
Phase II study design
Eligible patients with histological documented high grade Stage IIIB-IIIC-IV ovarian cancer regardless of residual tumor will be randomized 111 according to a molecular driven treatment
HRD positive patients
ARM B Carboplatin AUC 5 Paclitaxel 175 mgm2 q 21 for 6 cycles followed by Rucaparib 600 mg BID q 28 for 24 cycles as maintenance
ARM C Carboplatin AUC 5 Paclitaxel 175 mgm2 q 21 Bevacizumab 15 mgkg for 6 cycles followed by Bevacizumab 15 mgkg q 21 days for 16 cycles Bevacizumab will start from Cycle 2 Rucaparib 500 mg part BID q 28 for 24 cycles as maintenance
HRD negative patients
ARM A Carboplatin AUC 5 Paclitaxel 175 mgm2 q 21 Bevacizumab 15 mgkg for 6 cycles followed by Bevacizumab 15 mgkg q 21 for 16 cycles Bevacizumab will start from Cycle 2
ARM B Carboplatin AUC 5 Paclitaxel 175 mgm2 q 21 for 6 cycles followed by Rucaparib 600 mg BID q 28 for 24 cycles as maintenance
Stratification factors are
Residual tumor at primary surgery RT0 vs RT 0
Neoadiuvant chemotherapy Yes or not
This is a single-centre Phase I open-label dose-escalation study to evaluate the safety and tolerability of bevacizumab-rucaparib combination and determine the MTD in patients with advanced epithelial ovarian fallopian tube or primary peritoneal cancer
The dose of bevacizumab is fixed in cohort 1 2 and 3 of the study at 15mgkg q 3 weekly
The dose of rucaparib is evaluated in three cohorts 400 mg BID 500 mg BID 600 mg BID
This trial will enroll at least 3 patients in cohort 1 with dose escalation to rucaparib 500 mg from cohort 1 to 2 Cohort 2 will enroll at least 3 patients with dose escalation to rucaparib 600 mg from cohort 2 to 3
The standard 33 design will be used Patients will be enrolled in cohort of 3 patients if no DLT event will be reported among the first 3 patients a second cohort will be enrolled at the upper dose level If 1 DLT event is registered in the first cohort other 3 patients will be enrolled at the same dose
Phase II study design
Eligible patients with histological documented high grade Stage IIIB-IIIC-IV ovarian cancer regardless of residual tumor will be randomized 111 according to a molecular driven treatment
HRD positive patients
ARM B Carboplatin AUC 5 Paclitaxel 175 mgm2 q 21 for 6 cycles followed by Rucaparib 600 mg BID q 28 for 24 cycles as maintenance
ARM C Carboplatin AUC 5 Paclitaxel 175 mgm2 q 21 Bevacizumab 15 mgkg for 6 cycles followed by Bevacizumab 15 mgkg q 21 days for 16 cycles Bevacizumab will start from Cycle 2 Rucaparib 500 mg part BID q 28 for 24 cycles as maintenance
HRD negative patients
ARM A Carboplatin AUC 5 Paclitaxel 175 mgm2 q 21 Bevacizumab 15 mgkg for 6 cycles followed by Bevacizumab 15 mgkg q 21 for 16 cycles Bevacizumab will start from Cycle 2
ARM B Carboplatin AUC 5 Paclitaxel 175 mgm2 q 21 for 6 cycles followed by Rucaparib 600 mg BID q 28 for 24 cycles as maintenance
Stratification factors are
Residual tumor at primary surgery RT0 vs RT 0
Neoadiuvant chemotherapy Yes or not
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