Ignite Creation Date:
2024-06-16 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06439888
Status:
RECRUITING
Last Update Posted:
2024-07-12
First Post:
2024-05-28
Brief Title:
Lymphocyte Support to SBRT in Patients With Oligo-metastatic Solid Cancer
Sponsor:
Gustave Roussy Cancer Campus Grand Paris
Organization:
Gustave Roussy Cancer Campus Grand Paris
Study Overview
Official Title:
Pan-lesions SBRT Combined With Lymphocyte Support Through ATRA-driven Blockade of MDSC in Patients With Oligo-metastatic Solid Cancer
Status:
RECRUITING
Status Verified Date:
2024-07
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:
LySATRA
Brief Summary:
The goal of this clinical trial is to assess safety of pan-metastases directed SBRT combined with ATRA and the lympho-protective efficacy of ATRA upon radiation-induced lymphopenia
This is a French bicentric open label phase III clinical study that will comprise two parts Part I will evaluate the safety of the combination based on a single-arm safety run design while Part II will be randomized ratio 11 and will study SBRT with or without ATRA
Patients enrolled will be treated with
SBRT to all lesions more than 15cm on week days from Monday to Friday over a maximum of 2 weeks
With or without for part II patients randomized in the control arm ATRA therapy ATRA 150 mgm2day for 3 days every 3 weeks for a maximum of 4 cycles about 3 months starting on the first day of radiation therapy
The expected rate of patients who will have lymphopenia of grade 2 or higher in the control arm at 6 weeks post-radiotherapy is 50
At a one-sided level of statistical significance of 007 the randomization of 52 patients 26 patients in each arm will provide 85 power to detect a decrease in this rate to 15 in the SBRTATRA arm using Fishers exact test
This is a French bicentric open label phase III clinical study that will comprise two parts Part I will evaluate the safety of the combination based on a single-arm safety run design while Part II will be randomized ratio 11 and will study SBRT with or without ATRA
Patients enrolled will be treated with
SBRT to all lesions more than 15cm on week days from Monday to Friday over a maximum of 2 weeks
With or without for part II patients randomized in the control arm ATRA therapy ATRA 150 mgm2day for 3 days every 3 weeks for a maximum of 4 cycles about 3 months starting on the first day of radiation therapy
The expected rate of patients who will have lymphopenia of grade 2 or higher in the control arm at 6 weeks post-radiotherapy is 50
At a one-sided level of statistical significance of 007 the randomization of 52 patients 26 patients in each arm will provide 85 power to detect a decrease in this rate to 15 in the SBRTATRA arm using Fishers exact test
Detailed Description:
Ablative radiotherapy - also called stereotactic body radiation therapy SBRT - can achieve durable control of tumor lesions and appears as a highly promising strategy to extend overall survival of patients with oligo-metastatic diseases Radiotherapy has recognized immunomodulatory effects it triggers immunogenic cell death and reprogramming of the tumor immune microenvironment which eventually results in a systemic antitumor response following focal radiation treatment This is called the abscopal effect distant out-of-the-field lesions that shrink after focal irradiation Unfortunately evidences show that this is directly counteracted by the toxic effects of radiotherapy on cytotoxic lymphocytes which are highly radiosensitive
Recent data support the fact that radiation-induced lymphopenia is mostly driven by the deregulation of the myeloid-lymphoid imbalance following radiation therapy with aberrant myelopoiesis and high levels of tumor infiltration by myeloid-derived suppressive cells MDSC In preclinical models pharmacological blockade of MDSC combined with radiation therapy successfully abrogated radiation-induced lymphopenia and significantly improved survival outcomes
All trans retinoic acid ATRA also known as tretinoin is a vitamin A derivative that has a market authorization for the treatment of acute promyelocytic leukemia as it efficiently induces differentiation of abnormal promyelocytes Similarly several clinical studies report that ATRA can differentiate MDSCs into mature myeloid cells with a positive effect on the count of activated cluster of differentiation 8 CD8 lymphocytes
This clinical trial will provide the clinical proof-of-concept that adding ATRA to pan-metastases SBRT is safe in humans prevents severe and prolonged lymphopenia and therefore may foster a radiation-induced systemic anticancer immune response sufficient to increase survival in patients with cancer at the oligo-metastatic stage
Recent data support the fact that radiation-induced lymphopenia is mostly driven by the deregulation of the myeloid-lymphoid imbalance following radiation therapy with aberrant myelopoiesis and high levels of tumor infiltration by myeloid-derived suppressive cells MDSC In preclinical models pharmacological blockade of MDSC combined with radiation therapy successfully abrogated radiation-induced lymphopenia and significantly improved survival outcomes
All trans retinoic acid ATRA also known as tretinoin is a vitamin A derivative that has a market authorization for the treatment of acute promyelocytic leukemia as it efficiently induces differentiation of abnormal promyelocytes Similarly several clinical studies report that ATRA can differentiate MDSCs into mature myeloid cells with a positive effect on the count of activated cluster of differentiation 8 CD8 lymphocytes
This clinical trial will provide the clinical proof-of-concept that adding ATRA to pan-metastases SBRT is safe in humans prevents severe and prolonged lymphopenia and therefore may foster a radiation-induced systemic anticancer immune response sufficient to increase survival in patients with cancer at the oligo-metastatic stage
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 20223511 | OTHER | CSET number Gustave Roussy ID | None |