PARP Inhibition, Stereotactic Body Radiotherapy and Immunotherapy for Metastatic or Advanced Sarcoma (PRIMA)
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age10-70
SponsorRuijin Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Written informed consent signed before any trial-related procedures are carried out
Histologically confirmed high-grade sarcoma of bone or soft tissue; the lesion has distant metastasis or is locally advanced and cannot be completely resected at the time of enrollment, or the patient cannot tolerate or refuses surgical resection;
Have received at least one systemic treatment regimen(s) at the time of enrollment, and have not received prior PARP inhibitor treatment.
With measurable lesions according to Response Evaluation Criteria in Solid Tumors (RECIST1.1);
Disqualifiers
Diagnosed with malignant diseases other than tumors within 5 years before the first dose;
Currently participating in interventional clinical research treatment, or have received other research drugs or used research equipment within 4 weeks before the first dose;
Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs or drugs targeting another stimulating or synergistic inhibition of T cell receptors (e.g., CTLA-4, OX-40, CD137) drug and secondary resistance to the drug (i.e., the best efficacy evaluation is CR, PR or SD lasting more than 4 months, but secondary tumor resistance develops after treatment).
Received systemic systemic treatment with Chinese patent medicines with anti-tumor indications or drugs with immunomodulatory effects (including thymosin, interferon, interleukin, except local use to control pleural effusion) within 2 weeks before the first dose;
Trial design
Design model
Parallel
Treatments tested in this trial
Camrelizumab and fluzoparib with concurrent stereotactic body radiotherapy (SBRT)
Combination productPatients receive Camrelizumab (PD-1 inhibitor) and fluzoparib (PARP inhibitor) with concurrent stereotactic body radiotherapy (SBRT)
Treatment groups
86 Participants
are divided into 3 treatment groupsGroup A: Bone armExperimental treatment 1 intervention
Group B: Soft tissue armExperimental treatment 1 intervention
Group C: UPS/DDLPS armExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
6-momth progression-free survival rate (6m-PFSR)
The proportion of patients that are progression-free according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), defined as the ratio of patients who have not died or progressed (CR+PR+SD) over the total number of subjects recruited.
Time frame
6 months from recruitmentSecondary outcomes
1
Objective respones rate (ORR)
Defined as the number of subjects with a best response of (CR+PR)/total number of subjects\*100% based on RECISTv1.1 and irRECIST standards respectively
Time frame
From baseline to disease progression or death, whichever occurs first, until 3 years after accrual2
Disease control rate (DCR)
Defined as the number of subjects with a best response of (CR+PR+SD)/total number of subjects\*100% based on RECISTv1.1 and irRECIST standards respectively;
Time frame
From baseline to disease progression or death, whichever occurs first, up to 3 years after accrual3
Duration of response (DOR)
Defined as the interval from first time of response (CR or PR) until disease progression (PD) according to RECISTv1.1 and irRECIST standards respectively, and estimated by the Kaplan-Meier method, including median, Interquartiles and 95% confidence intervals
Time frame
From baseline to disease progression or death, whichever occurs first, up to 3 years after accrual4
Progression-free survival (PFS)
Defined as the time from receiving the first study drug to the death or relapse of the subject, assessed by RECISTv1.1 and irRECIST standards respectively, and estimated by the Kaplan-Meier method, including median, quartile and 95% confidence interval
Time frame
From baseline to disease progression or death, whichever occurs first, up to 3 years after accrualOther outcomes
1
Exploratory outcome: progression-free survival(PFS) in different subgroup
The PFS for each subgroups in terms of clinicopathological and genomic characteristics (age, gender, histological type, solitary or multiple metastases, unilateral or bilateral metastases, early or late metastases, calcifying or non-calcifying lesions, with or without lesion cavitation, with or without AEs, etc.
Time frame
From baseline to disease progression or death, whichever occurs first, up to 3 years after accrual.2
Exploratory outcome: the homologous recombination deficiency (HRD) score in tumor samples
The correlative relationship between the tumor response and the genomic biomarker (i.e. homologous recombination-related \[HRR\] gene mutation, homologous recombination deficiency (HRD) score (LOH+TAI+LST), and RAD51 functional testing) and the therapeutic outcome.
Time frame
From baseline to disease progression or death, whichever occurs first, up to 3 years after accrual3
Exploratory outcome: the expression of immune infiltration biomarker in tumor samples
Tumor microenvironment change (immune infiltration, PD-1/PD-L1 expression, immunogenic death, etc.) pre- and post- SBRT, and conduct correlative analysis between these immune microenvironment indeces and the therapeutic outcome.
Time frame
From baseline to disease progression or death, whichever occurs first, up to 3 years after accrual.Sponsors and contacts
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Source ClinicalTrials.gov