Ignite Creation Date:
2024-05-06 @ 3:54 PM
Last Modification Date:
2024-10-26 @ 2:00 PM
Study NCT ID:
NCT04807192
Status:
RECRUITING
Last Update Posted:
2021-07-09
First Post:
2021-02-12
Brief Title:
CMP-001 and Pre-operative Stereotactic Body Radiation Therapy SBRT in Early Stage Triple Negative Breast Cancer TNBC
Sponsor:
Centre Hospitalier Universitaire Vaudois
Organization:
Centre Hospitalier Universitaire Vaudois
Study Overview
Official Title:
CMP-001 in Combination With Pre-Operative Stereotactic Body Radiation Therapy in Patients With Early Stage Triple Negative Breast Cancer An Open-Label Window of Opportunity Randomized Phase 2 Clinical Study
Status:
RECRUITING
Status Verified Date:
2021-07
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:
None
Brief Summary:
This is an open-label randomized window-of-opportunity phase 2 clinical study evaluating the biological activity of preoperative Stereotactic Body RadioTherapy SBRT alone Arm 1 and combined with subcutaneous SC followed by intra-tumoral IT administrations of CMP-001 Arm 2 in subjects with early stage TNBC Safety and efficacy of the treatments are also examined
The main hypothesis that the study treatment induces an increase in stromal tumor infiltrating lymphocytes sTILs will be explored in each arm separately
The study is designed as a randomized selection study with randomization used to address patient selection bias while each arm is run as an independent study No formal statistical comparison between the two arms is planned
40 patients will be equally 11 randomized in this study 20 per arm
The main hypothesis that the study treatment induces an increase in stromal tumor infiltrating lymphocytes sTILs will be explored in each arm separately
The study is designed as a randomized selection study with randomization used to address patient selection bias while each arm is run as an independent study No formal statistical comparison between the two arms is planned
40 patients will be equally 11 randomized in this study 20 per arm
Detailed Description:
This is a Phase 2 proof of principle study that explores the therapeutic window between diagnosis and surgery in patients with early stage invasive TNBC not being candidates for neo-adjuvant chemotherapy
The presence of tumor infiltrating lymphocytes TILs within the tumors of patients with early invasive TNBC has been associated with improved prognosis The hypothesis of this study is that pre-operative SBRT with or without CpG CMP-001 a toll-like receptor TLR 9 agonist will induce an increase in sTILs in the tumor in patients with early invasive TNBC which theoretically should improve those patients prognosis
There is growing evidence indicating that radiotherapy RT induces massive release of tumor-associated antigens TAAs during cancer cell death RT enhances tumor immunogenicity and increases the presence of effector immune cells to the tumor site It increases availability of tumor antigens and promotes antigen capture cell migration to the lymph nodes polarization towards a tolerogenic or immunogenic phenotype or migration of lymphocytes into the tumor Doses of around 8 Gy induce more important immune infiltration
SBRT is a precise technique of irradiation within the tumor permitting high dose delivery in a safe manner with tight margins In our study the irradiated tissue will then be removed by surgery allowing for standard of care irradiation to be administered postoperatively However the preoperative SBRT on the tumor might increase intratumoral or stromal TILs presence
CMP-001 has already been shown to increase CD8 T cell intratumoral infiltration in early clinical data and ongoing data of a phase Ib clinical trial combining intratumoral IT injections of CMP-001 3-10 mg in melanoma lesions with Pembrolizumab show rapid abscopal responses in other skin lesions after 3 injections The combination of IT CMP-001 and SBRT through increased TAA release and immunologic enhancement due to the TLR9 agonist might ultimately result in a clinically meaningful in-situ vaccination effect through enhancement of the hosts antitumor immunity promoting immune eradication of micrometastatic disease The TNBC population is prone to micrometastatic disease even at early stages therefore any of these experimental treatments might result in increased TILs infiltration which theoretically would bring potential benefits in distant control of the disease and overall survival improvements
The presence of tumor infiltrating lymphocytes TILs within the tumors of patients with early invasive TNBC has been associated with improved prognosis The hypothesis of this study is that pre-operative SBRT with or without CpG CMP-001 a toll-like receptor TLR 9 agonist will induce an increase in sTILs in the tumor in patients with early invasive TNBC which theoretically should improve those patients prognosis
There is growing evidence indicating that radiotherapy RT induces massive release of tumor-associated antigens TAAs during cancer cell death RT enhances tumor immunogenicity and increases the presence of effector immune cells to the tumor site It increases availability of tumor antigens and promotes antigen capture cell migration to the lymph nodes polarization towards a tolerogenic or immunogenic phenotype or migration of lymphocytes into the tumor Doses of around 8 Gy induce more important immune infiltration
SBRT is a precise technique of irradiation within the tumor permitting high dose delivery in a safe manner with tight margins In our study the irradiated tissue will then be removed by surgery allowing for standard of care irradiation to be administered postoperatively However the preoperative SBRT on the tumor might increase intratumoral or stromal TILs presence
CMP-001 has already been shown to increase CD8 T cell intratumoral infiltration in early clinical data and ongoing data of a phase Ib clinical trial combining intratumoral IT injections of CMP-001 3-10 mg in melanoma lesions with Pembrolizumab show rapid abscopal responses in other skin lesions after 3 injections The combination of IT CMP-001 and SBRT through increased TAA release and immunologic enhancement due to the TLR9 agonist might ultimately result in a clinically meaningful in-situ vaccination effect through enhancement of the hosts antitumor immunity promoting immune eradication of micrometastatic disease The TNBC population is prone to micrometastatic disease even at early stages therefore any of these experimental treatments might result in increased TILs infiltration which theoretically would bring potential benefits in distant control of the disease and overall survival improvements
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