Ignite Creation Date:
2024-05-06 @ 8:19 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06336291
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-06
First Post:
2024-03-04
Brief Title:
A Study With L19TNF in Combination With Lomustine in Patients With Glioblastoma at Progression or Recurrence
Sponsor:
Philogen SpA
Organization:
Philogen SpA
Study Overview
Official Title:
A Dose Optimization Study for L19TNF in Combination With Lomustine in Patients With Glioblastoma at Progression or Recurrence
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
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:
GLIOSTELLA
Brief Summary:
The trial aims to collect safety efficacy exposure dose- response pharmacokinetic and pharmacodynamic information of the combination of L19TNF and lomustine at different dose levels in patients with Glioblastoma at progression or recurrence
Detailed Description:
The present study is a randomized open-label non-controlled phase II study in patients with glioblastoma at any progressionrecurrence first and later
Overall 90 subjects will be enrolled and parallel assigned in a 11 fashion to one of six treatment arms from A to F of 15 patients each
Each arm has a different combination of L19TNF 7 μgkg or 10 μgkg or 13 μgkg and lomustine at different dose levels 90 or 110 mgm2
Treatment is based on a 42-day cycle for up to a maximum of 6 cycles
This is an open-label study so there is no blinding
Patients who successfully complete the screening evaluations and are eligible for participation in the study will be enrolled and randomly assigned 111111 to either of the six parallel treatment arms
To maintain an appropriate balance between the six treatment arms and avoid undesired confounding effect of different factors patients will be randomized in accordance with the following strata
MGMT status
Steroid administration
Previous systemic therapy treatment for progression
A randomization list will be prepared for each stratum using permuted block the block sizes will be chosen randomly from different pre-specified sizes with an equal treatment allocation ratio The labels for the arms are assigned randomly within each block fixed seed The obtained final list is sorted by block together with the progressive enrollment number for the patients
The primary objective of this study is to select the optimal regimen of L19TNF in combination with lomustine that maximizes effects on clinical parameters and minimizes the probability of moderate to severe adverse events among six three L19TNF doses x two lomustine doses combination schedules for the treatment of patient with progressing or recurrent glioblastoma
Primary endpoints include Safety Incidence of adverse Events AEs Serious Adverse Events SAEs and Drug-Induced Liver Injury DILI standard laboratory assessments ECG ECHO and physical examination according to CTCAE v50 and Efficacy Survival rate at 12 months
The secondary objective of this study is to further evaluate safety efficacy exposure dose-response pharmacokinetic and pharmacodynamic information of the combination of L19TNF and lomustine at different dose levels to determine the best dose regimen for further studies
During the conduct of the study the safety information collected will be routinely reviewed by the Data and Safety Monitoring Board DSMB in order to identify possible safety concerns
If the probability in a treatment arm that the development of unacceptable toxicity rate exceeds 33 is equal or higher than 80 the recruitment to this treatment arm will be interrupted and the DSMB will be informed to assess the events and relationship to the study treatment The DSMB may then recommend to re-start recruitment again for the treatment arm or permanently suspend it
In case of a treatment-related death recruitment will be suspended for all treatment arms until the Data and Safety Monitoring Board DSMB has reviewed the event and recommended to restart
Overall 90 subjects will be enrolled and parallel assigned in a 11 fashion to one of six treatment arms from A to F of 15 patients each
Each arm has a different combination of L19TNF 7 μgkg or 10 μgkg or 13 μgkg and lomustine at different dose levels 90 or 110 mgm2
Treatment is based on a 42-day cycle for up to a maximum of 6 cycles
This is an open-label study so there is no blinding
Patients who successfully complete the screening evaluations and are eligible for participation in the study will be enrolled and randomly assigned 111111 to either of the six parallel treatment arms
To maintain an appropriate balance between the six treatment arms and avoid undesired confounding effect of different factors patients will be randomized in accordance with the following strata
MGMT status
Steroid administration
Previous systemic therapy treatment for progression
A randomization list will be prepared for each stratum using permuted block the block sizes will be chosen randomly from different pre-specified sizes with an equal treatment allocation ratio The labels for the arms are assigned randomly within each block fixed seed The obtained final list is sorted by block together with the progressive enrollment number for the patients
The primary objective of this study is to select the optimal regimen of L19TNF in combination with lomustine that maximizes effects on clinical parameters and minimizes the probability of moderate to severe adverse events among six three L19TNF doses x two lomustine doses combination schedules for the treatment of patient with progressing or recurrent glioblastoma
Primary endpoints include Safety Incidence of adverse Events AEs Serious Adverse Events SAEs and Drug-Induced Liver Injury DILI standard laboratory assessments ECG ECHO and physical examination according to CTCAE v50 and Efficacy Survival rate at 12 months
The secondary objective of this study is to further evaluate safety efficacy exposure dose-response pharmacokinetic and pharmacodynamic information of the combination of L19TNF and lomustine at different dose levels to determine the best dose regimen for further studies
During the conduct of the study the safety information collected will be routinely reviewed by the Data and Safety Monitoring Board DSMB in order to identify possible safety concerns
If the probability in a treatment arm that the development of unacceptable toxicity rate exceeds 33 is equal or higher than 80 the recruitment to this treatment arm will be interrupted and the DSMB will be informed to assess the events and relationship to the study treatment The DSMB may then recommend to re-start recruitment again for the treatment arm or permanently suspend it
In case of a treatment-related death recruitment will be suspended for all treatment arms until the Data and Safety Monitoring Board DSMB has reviewed the event and recommended to restart
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