Ignite Creation Date:
2024-05-06 @ 8:26 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06385548
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-10
First Post:
2024-04-11
Brief Title:
Efficacy and Safety Study of Lurbinectedin and Dostarlimab in Cancer Patients Protocol VHIO21001 - LiDer
Sponsor:
Vall dHebron Institute of Oncology
Organization:
Vall dHebron Institute of Oncology
Study Overview
Official Title:
Phase I-II Study to Evaluate the Safety Tolerability and Efficacy of Lurbinectedin and Dostarlimab in Patients With AdvancedRecurrent Endometrial Cancer With Disease Progression Following Previous Platinum Chemotherapy Therapy
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-04
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:
LiDer
Brief Summary:
Background
Endometrial cancer is a prevalent gynecological malignancy with a significant number of cases diagnosed at an advanced stage or recurring following initial treatment Platinum-based chemotherapy represents a standard treatment option for these patients however disease progression often occurs highlighting the need for novel therapeutic approaches Lurbinectedin a synthetic analog of marine alkaloid-derived compounds and dostarlimab a monoclonal antibody targeting PD-1 have demonstrated promising antitumor activity in various malignancies This phase I-II clinical trial seeks to evaluate the safety tolerability and efficacy of combining lurbinectedin and dostarlimab in patients with advanced or recurrent endometrial cancer who have experienced disease progression following platinum-based chemotherapy
Primary Objectives
To determine the maximum tolerated dose MTD and recommended dose for further investigation of lurbinectedin and dostarlimab in combination therapy for advanced or recurrent endometrial cancer
To assess the antitumor activity of lurbinectedin and dostarlimab combination therapy measured by objective response rate ORR in patients with advanced or recurrent endometrial cancer
Secondary Objectives
To evaluate the safety and tolerability of lurbinectedin and dostarlimab combination therapy in patients with advanced or recurrent endometrial cancer
To characterize the pharmacokinetic profile of lurbinectedin and dostarlimab when administered in combination therapy
To explore pharmacogenomic biomarkers predictive of response andor resistance to lurbinectedin and dostarlimab combination therapy in patients with advanced or recurrent endometrial cancer
To assess progression-free survival PFS duration of response DOR clinical benefit rate CBR and overall survival OS in patients receiving lurbinectedin and dostarlimab combination therapy for advanced or recurrent endometrial cancer
To investigate the impact of lurbinectedin and dostarlimab combination therapy on quality of life and symptom control in patients with advanced or recurrent endometrial cancer
Endometrial cancer is a prevalent gynecological malignancy with a significant number of cases diagnosed at an advanced stage or recurring following initial treatment Platinum-based chemotherapy represents a standard treatment option for these patients however disease progression often occurs highlighting the need for novel therapeutic approaches Lurbinectedin a synthetic analog of marine alkaloid-derived compounds and dostarlimab a monoclonal antibody targeting PD-1 have demonstrated promising antitumor activity in various malignancies This phase I-II clinical trial seeks to evaluate the safety tolerability and efficacy of combining lurbinectedin and dostarlimab in patients with advanced or recurrent endometrial cancer who have experienced disease progression following platinum-based chemotherapy
Primary Objectives
To determine the maximum tolerated dose MTD and recommended dose for further investigation of lurbinectedin and dostarlimab in combination therapy for advanced or recurrent endometrial cancer
To assess the antitumor activity of lurbinectedin and dostarlimab combination therapy measured by objective response rate ORR in patients with advanced or recurrent endometrial cancer
Secondary Objectives
To evaluate the safety and tolerability of lurbinectedin and dostarlimab combination therapy in patients with advanced or recurrent endometrial cancer
To characterize the pharmacokinetic profile of lurbinectedin and dostarlimab when administered in combination therapy
To explore pharmacogenomic biomarkers predictive of response andor resistance to lurbinectedin and dostarlimab combination therapy in patients with advanced or recurrent endometrial cancer
To assess progression-free survival PFS duration of response DOR clinical benefit rate CBR and overall survival OS in patients receiving lurbinectedin and dostarlimab combination therapy for advanced or recurrent endometrial cancer
To investigate the impact of lurbinectedin and dostarlimab combination therapy on quality of life and symptom control in patients with advanced or recurrent endometrial cancer
Detailed Description:
This study is a phase I-II clinical trial conducted to evaluate the safety tolerability and efficacy of lurbinectedin and dostarlimab combination therapy in patients with advanced or recurrent endometrial cancer The trial follows a multicenter open-label design and comprises two phases a dose escalation phase Phase I and an expansion phase Phase II The primary endpoints include determining the maximum tolerated dose MTD recommended dose for further investigation and objective response rate ORR Secondary endpoints encompass safety pharmacokinetics pharmacogenomics progression-free survival PFS duration of response DOR clinical benefit rate CBR overall survival OS and quality of life assessments
Study Treatments
Lurbinectedin Lurbinectedin is administered as a lyophilized powder for concentrate for infusion reconstituted with sterile water for injection to achieve a concentration of 05 mgmL The initial dose for infusion is 26 mgm2 diluted in either 5 glucose solution or 09 sodium chloride solution During Phase I dose adjustments are based on body surface area calculated using the DuBois formula
Dostarlimab Dostarlimab is supplied in vials containing 500 mg at a concentration of 50 mgmL The recommended dose is a fixed dose of 500 mg administered intravenously over 30 minutes Treatment cycles consist of administration on Day 1 of a 21-day cycle with dostarlimab followed by lurbinectedin in combination therapy
During the dose escalation phase Phase I a predefined dose escalation scheme is employed starting with dose level DL -1 and progressing to DL1 DL2 and subsequent levels as per the protocol Dose escalation is guided by the occurrence of dose-limiting toxicities DLTs and the determination of the MTD Once the MTD is established the expansion phase Phase II begins wherein additional patients receive treatment at the recommended dose to further evaluate safety and efficacy outcomes
Study Treatments
Lurbinectedin Lurbinectedin is administered as a lyophilized powder for concentrate for infusion reconstituted with sterile water for injection to achieve a concentration of 05 mgmL The initial dose for infusion is 26 mgm2 diluted in either 5 glucose solution or 09 sodium chloride solution During Phase I dose adjustments are based on body surface area calculated using the DuBois formula
Dostarlimab Dostarlimab is supplied in vials containing 500 mg at a concentration of 50 mgmL The recommended dose is a fixed dose of 500 mg administered intravenously over 30 minutes Treatment cycles consist of administration on Day 1 of a 21-day cycle with dostarlimab followed by lurbinectedin in combination therapy
During the dose escalation phase Phase I a predefined dose escalation scheme is employed starting with dose level DL -1 and progressing to DL1 DL2 and subsequent levels as per the protocol Dose escalation is guided by the occurrence of dose-limiting toxicities DLTs and the determination of the MTD Once the MTD is established the expansion phase Phase II begins wherein additional patients receive treatment at the recommended dose to further evaluate safety and efficacy outcomes
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