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SarcomaPhase 2PRIMANCT06074692

PARP Inhibition, Stereotactic Body Radiotherapy and Immunotherapy for Metastatic or Advanced Sarcoma (PRIMA)

A Phase 2 study testing Camrelizumab and fluzoparib with concurrent stereotactic body radiotherapy (SBRT) in people with Sarcoma and Sarcoma,Soft Tissue, run by Ruijin Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 10 to 70 years
Conditions the study is for
Sarcoma, Sarcoma,Soft Tissue, Sarcoma of Bone
What is being tested?
Camrelizumab and fluzoparib with concurrent stereotactic body radiotherapy (SBRT)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
86 participants
Where
1 siteChina
Study dates
1 Jun 2023to 30 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 to 70 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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);
  • Aged no less than 10 years old and no more than 70 years old;
  • For patients ≥16 years old, ECOG score is between 0 and 2 (for patients with amputations, if they can basically take care of themselves and can move freely for more than 50% of their waking hours with the assistance of stretchers, walkers, wheelchairs, etc.) still included);
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  • For patients under 16 years old, Lansky score is at least 70 or above (for patients with amputations who are unable to participate in active recreational activities due to amputation), if they can participate in most active recreational activities with the assistance of walkers, wheelchairs, etc., they are still eligible included).
  • The expected survival time is greater than 24 weeks;
  • The majority of the recurrent lesions with an established radiological diagnosis could receive SBRT;
  • Major organ functions meet basic safety standards within 7-14 days before treatment.
  • Women of childbearing age should agree that they must use contraceptive measures (such as intrauterine devices, birth control pills or condoms) during the study and within 6 months after the end of the study; if in doubt, serum or urine tests within 7 days before study enrollment The pregnancy test is negative and the patient must be non-lactating; the male should agree that contraceptive measures must be used during the study period and within 6 months after the end of the study period;
  • If there are recurrent lesions previously treated by surgery, radiofrequency ablation or radiotherapy:
  • If the image of the metastatic lesion is stable, enrollment is allowed and SBRT is not required for that lesion;
  • If the metastatic lesion has image progression, if it was previously treated with surgery and SBRT can be performed, enrollment is allowed; if it was previously treated with radiofrequency ablation or radiotherapy, if repeat SBRT can be considered, enrollment is allowed.

Who cannot join

  • 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;
  • Active autoimmune disease requiring systemic treatment (such as use of disease-modifying drugs, glucocorticoids, or immunosuppressants) within 2 years before the first dose. Replacement therapies (such as thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) are not considered systemic treatments;
  • Are receiving systemic glucocorticoid treatment (excluding nasal spray, inhaled or other route of topical glucocorticoids) or any other form of immunosuppressive therapy within 7 days before the first dose of the study;
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  • Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
  • Known to be allergic to any components of monoclonal antibody preparations (have experienced grade 3 or above allergic reactions);
  • Have not fully recovered from toxicity and/or complications caused by any intervention before initiating treatment (i.e., ≤Grade 1 or reaching baseline, excluding fatigue or alopecia);
  • Known history of human immunodeficiency virus (HIV) infection (i.e. HIV1/2 antibody positive);
  • Get live vaccine within 30 days before the first dose (cycle 1, day 1);
  • Pregnant or lactating women;
  • Any serious or uncontrollable systemic disease

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Weibin Zhang, PhD, MD contact

+8613501824630

zhangweibin10368@163.com

Yuhui Shen, PhD, MD contact

+8613918209875

yuhuiss@163.com

China1 site, 1 recruiting
  • Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine

    Shanghai, Shanghai Municipality, 20025

    Qiyuan Bao, MD., Ph.D, +86 13818971504, rblw_110@hotmail.com

    Recruiting

Other trials in China

About this study

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

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.

Read the 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.

Being tested
Camrelizumab and fluzoparib with concurrent stereotactic body radiotherapy (SBRT)
Keywords
sarcoma, bone and soft tissue sarcoma, PARP inhibitor, SBRT, checkpoint inhibitor
Medical subject headings
Sarcoma, Osteosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Camrelizumab and fluzoparib with concurrent stereotactic body radiotherapy (SBRT)Combination product

    Patients receive Camrelizumab (PD-1 inhibitor) and fluzoparib (PARP inhibitor) with concurrent stereotactic body radiotherapy (SBRT)

Study groups in NCT06074692
Study groupRoleWhat they receive
Bone armExperimentalBone tumor subgroup (bone arm) includes high-grade osteosarcoma, chondrosarcoma, undifferentiated bone sarcoma and other rare bone sarcomas with complex genomic features..
Receives: Combination Product: Camrelizumab and fluzoparib with concurrent stereotactic body radiotherapy (SBRT)
Soft tissue armExperimentalSoft tissue sarcoma subgroup (soft tissue arm) includes leiomyosarcoma, pleomorphic rhabdomyosarcoma, angiosarcoma, fibrosarcoma, epithelioid sarcoma, malignant peripheral nerve sheath tumor(MPNST) and other rare soft tissue sarcomas with complex genomic features.
Receives: Combination Product: Camrelizumab and fluzoparib with concurrent stereotactic body radiotherapy (SBRT)
UPS/DDLPS armExperimentalImmune hot tumor subgroup (UPS/DDLPS arm) includes undifferentiated pleomorphic sarcoma (UPS), dedifferentiated liposarcoma (DDLPS).
Receives: Combination Product: Camrelizumab and fluzoparib with concurrent stereotactic body radiotherapy (SBRT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 months from recruitment

Secondary outcomes (7)
  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

    Measured: From baseline to disease progression or death, whichever occurs first, until 3 years after accrual

  2. 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;

    Measured: From baseline to disease progression or death, whichever occurs first, up to 3 years after accrual

  3. 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

    Measured: From baseline to disease progression or death, whichever occurs first, up to 3 years after accrual

  4. 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

    Measured: From baseline to disease progression or death, whichever occurs first, up to 3 years after accrual

  5. Overall survival (OS)

    defined as the time from receiving the first study drug treatment to the subject's death, estimated by the Kaplan-Meier method, including median, quartile and 95% confidence interval;

    Measured: From baseline until the reported death of the patients due to any causes, up to 3 years after accrual

  6. Quality of life assessed by patient-reported outcomes (PROs)

    The quality of life score using PROs based on EORTC QLQ-C30 scale (adult) or Paediatric Quality of Life Inventory (PedsQL) scale at baseline and at each followed up after treatment.

    Measured: From baseline until the reported death of the patients due to any causes, up to 3 years after accrual

  7. Number of participants with adverse events

    Number of participants with Treatment emergent adverse events (TEAE) and serious adverse events (SAE). AE was defines as any toxicities in a participant who received study therapy irrespective of the causal relationship. SAE was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity or inpatient hospitalization or prolongation of existing hospitalization.

    Measured: From the first dose of study treatment to 30 days after the last dose of study treatment or before the start day of new anti-cancer drug therapy, whichever occurs first, up to 3 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Oct 2023
  2. Study start1 Jun 2023
  3. Primary completion30 Aug 2026 (estimated)
  4. Study completion30 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
86 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06074692
Sponsor's protocol ID
2023-LLS-220
Acronym
PRIMA
Status last verified
Oct 2023
First submitted
3 Oct 2023
Last updated
31 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: individual participant data (IPD) will be available to academic research upon reasonable request, under the local offical rules and regulations.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Camrelizumab and fluzoparib with concurrent stereotactic body radiotherapy (SBRT) in people with Sarcoma and Sarcoma,Soft Tissue, run by Ruijin Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 31 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Weibin Zhang, PhD, MD (+8613501824630, zhangweibin10368@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

6-momth progression-free survival rate (6m-PFSR) (time frame: 6 months from recruitment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2023.

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