Ignite Creation Date:
2025-12-24 @ 3:28 PM
Ignite Modification Date:
2026-01-03 @ 6:50 PM
Study NCT ID:
NCT06074692
Status:
RECRUITING
Last Update Posted:
2023-10-31
First Post:
2023-10-03
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
PARP Inhibition, Stereotactic Body Radiotherapy and Immunotherapy for Metastatic or Advanced Sarcoma (PRIMA)
Sponsor:
Ruijin Hospital
Organization:
Study Overview
Official Title:
A Prospective Phase II Study of PARP Inhibition and Check Point-inhibition Immunotherapy With Concurrent Stereotactic Body Radiotherapy (SBRT) in Patients With Metastatic or Advanced Sarcoma
Status:
RECRUITING
Status Verified Date:
2023-10
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:
PRIMA
Brief Summary:
The aim of this study is to evaluate the efficacy and safety of PARP Inhibition and programmed cell death protein-1 (PD-1) blockade immunotherapy with concurrent stereotactic body radiotherapy (SBRT) for metastatic or advanced bone and soft tissue sarcoma.
Detailed Description:
Bone and soft tissue sarcomas are a group of highly heterogeneous malignant tumors that originate from mesenchymal tissue. The recurrent and metastatic sarcomas are usually refractory to traditional radiotherapy and chemotherapy, with a five-year survival rate is less than 20% to 30%. Therefore, novel therapy targeting the molecular phenotypic characteristics of bone and soft tissue sarcomas and conduct personalized and precise treatment for specific target patient subgroups is one of the important directions in the current clinical and translational fields.
Studies based on the anti-cancer mechanism of synthetic lethality have shown that tumor cells with BRCA1 or BRCA2 gene mutations are very sensitive to the action of PARP inhibitors. Interestingly, recent research results have shown that many other tumor types besides gynecological tumors can also exhibit BRCA-like phenotypes (BRCAness) and genomic instability (GI). Among them, BRCAness is a subtype of bone and soft tissue sarcoma with poor prognosis. Although such patients rarely carry BRCA gene mutations, they can still potentially benefit from treatment with drugs related to DNA damage and synthetic lethality, such as PARP inhibitors. In addition, the latest research shows that the BRCA-like phenotype in sarcoma is related to immunosuppression in its tumor microenvironment and targeted intervention of the PARP pathway is likely to have a potential immune sensitizing effect on the tumor microenvironment of sarcoma. Our previous study based on 264 samples also suggested that in sarcoma subtypes with genomic complexity, tumor cells often demonstrated high GI characteristics, and the corresponding tumor transcriptomes exhibited BRCAness. Furthermore, the investigators established 8 cases of patient-derived sarcoma primary cell model (PTCC) through tumor biopsy samples and observed a high sensitivity to DNA damage in sarcoma habouring BRCAness.
In recent years, studies have found that when radiotherapy is given to local tumor lesions, Abscopal effect could be elicited by the immunogenic death of the local tumor. The investigators recently reviewed the clinical prognosis of 44 patients with advanced bone and soft tissue sarcoma treated with stereotactic body radiation therapy (SBRT) in our institute and found that the tumor response rate to the immune checkpoint inhibitor appears to be significantly increased after SBRT. Based on these findings, the investigators speculate that the combination of SBRT and PARP inhibition regimens could potentially boost the immunogenic death and further improve the immunotherapy response in metastatic or advanced sarcomas.
In this clinical trial, the investigators aim to evaluate the efficacy and safety of PARP Inhibition and programmed cell death protein-1 (PD-1) blockade immunotherapy with concurrent stereotactic body radiotherapy (SBRT) for metastatic or advanced bone and soft tissue sarcoma as a phase II clinical study. Meanwhile, the investigators evaluated the patient's tumor gene mutation, homologous recombination deficiency (HRD) score, and RAD51 functional testing and other aspects for correlative biomarker exploration, providing a theoretical basis for molecular precision treatment of bone and soft tissue sarcoma with PARP inhibitiors.
Studies based on the anti-cancer mechanism of synthetic lethality have shown that tumor cells with BRCA1 or BRCA2 gene mutations are very sensitive to the action of PARP inhibitors. Interestingly, recent research results have shown that many other tumor types besides gynecological tumors can also exhibit BRCA-like phenotypes (BRCAness) and genomic instability (GI). Among them, BRCAness is a subtype of bone and soft tissue sarcoma with poor prognosis. Although such patients rarely carry BRCA gene mutations, they can still potentially benefit from treatment with drugs related to DNA damage and synthetic lethality, such as PARP inhibitors. In addition, the latest research shows that the BRCA-like phenotype in sarcoma is related to immunosuppression in its tumor microenvironment and targeted intervention of the PARP pathway is likely to have a potential immune sensitizing effect on the tumor microenvironment of sarcoma. Our previous study based on 264 samples also suggested that in sarcoma subtypes with genomic complexity, tumor cells often demonstrated high GI characteristics, and the corresponding tumor transcriptomes exhibited BRCAness. Furthermore, the investigators established 8 cases of patient-derived sarcoma primary cell model (PTCC) through tumor biopsy samples and observed a high sensitivity to DNA damage in sarcoma habouring BRCAness.
In recent years, studies have found that when radiotherapy is given to local tumor lesions, Abscopal effect could be elicited by the immunogenic death of the local tumor. The investigators recently reviewed the clinical prognosis of 44 patients with advanced bone and soft tissue sarcoma treated with stereotactic body radiation therapy (SBRT) in our institute and found that the tumor response rate to the immune checkpoint inhibitor appears to be significantly increased after SBRT. Based on these findings, the investigators speculate that the combination of SBRT and PARP inhibition regimens could potentially boost the immunogenic death and further improve the immunotherapy response in metastatic or advanced sarcomas.
In this clinical trial, the investigators aim to evaluate the efficacy and safety of PARP Inhibition and programmed cell death protein-1 (PD-1) blockade immunotherapy with concurrent stereotactic body radiotherapy (SBRT) for metastatic or advanced bone and soft tissue sarcoma as a phase II clinical study. Meanwhile, the investigators evaluated the patient's tumor gene mutation, homologous recombination deficiency (HRD) score, and RAD51 functional testing and other aspects for correlative biomarker exploration, providing a theoretical basis for molecular precision treatment of bone and soft tissue sarcoma with PARP inhibitiors.
Study Oversight
Has Oversight DMC:
True
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?: