Combining Fluzoparib and Dalpiciclib for Advanced Sarcoma Treatment

A Single-center, Prospective, Single-arm Phase Ib/II Clinical Study on the Efficacy and Safety of Fluzoparib Combined With Dalpiciclib in the Treatment of Locally Advanced or Metastatic Sarcoma r

This study is testing a new combination of two drugs, Fluzoparib and Dalpiciclib, to see if they can safely help people with advanced sarcoma that has specific genetic changes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 12 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT05952128 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of Fluzoparib, a PARP inhibitor, in combination with Dalpiciclib, a CDK4/6 inhibitor, for patients with locally advanced or metastatic sarcoma. The study is divided into two phases: the first phase focuses on determining the maximum tolerated dose and dose-limiting toxicity, while the second phase evaluates the treatment's effectiveness. The trial aims to target sarcomas that are deficient in homologous recombination repair due to BRCA mutations, which may enhance the treatment response. Participants will be closely monitored for both safety and therapeutic outcomes.

Who should consider this trial

Good fit: Ideal candidates include patients aged 12 to 75 with locally advanced or metastatic sarcomas confirmed by histopathology.

Not a fit: Patients with sarcomas that do not exhibit BRCA mutations or those with severe organ dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and quality of life for patients with advanced sarcoma.

How similar studies have performed: While the combination of PARP and CDK4/6 inhibitors is a novel approach, previous studies have shown promise in targeting similar pathways in other cancers.

Eligibility criteria

Inclusion Criteria:1.Patients aged 12 to 75 years, male and female ; 2.Eastern Cooperative Oncology Group ( ECOG ) physical status score was 0-2 ; 3.Locally advanced or metastatic sarcomas ( including osteosarcoma, Ewing sarcoma, undifferentiated sarcoma, liposarcoma, leiomyosarcoma, fibrosarcoma and synovial sarcoma ) confirmed by histopathology, and at least one measurable lesion without local treatment ( according to RECIST v1.1, the long diameter of the measurable lesion mesured by spiral CT scan should be≥ 10 mm or the short diameter of the lymph node lesion should be ≥ 15 mm ) ; 4.Life expectancy≥ 12 weeks ; 5.The main organ function is basically normal and meets the program requirements :

a)Blood examination : (without blood transfusion within 14 days before screening, without using granulocyte colony stimulating factor \[ G-CSF \], or other methods to correct bone marrow suppression within 7 days ) ,Blood indicators should meet: i.hemoglobin ≥ 90 g / L ; ii.neutrophil count ≥ 1.5 × 109 / L ; iii.Platelet count ≥ 75 × 109 / L ; b)b. Biochemical examination : ( no albumin transfusion within 14 days ) indicators should meet: i.albumin ≥ 29 g / L ; ii.Alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) ≤ 2.5 times the upper limit of normal ( ULN ) ; iii.total bilirubin ( TBIL ) ≤ 1.5 times ULN ; iv.Creatinine Cr ≤ 1.5 times ULN or Cr clearance \> 50 mL / min; v.Urine protein \< 2 +. If Urine protein ≥ 2 +, an 24 hours ( h ) urine protein quantification test should be taken, and 24h urine protein quantification \< 1.0 g is allowed to include ) ; c)Coagulation function : activated partial thromboplastin time ( APTT ) and international normalized ratio ( INR ) ≤ 1.5 × ULN ( for those who regularly use anticoagulant therapy such as low molecular weight heparin or warfarin and INR meets the expected requirement are allowed to include ) ; d)Thyroid stimulating hormone ( TSH ) ≤ ULN ; If not, T3 and T4 levels should be examined, and only with normal T3 and T4 level is allowed to include.

e)Echocardiography : left ventricular ejection fraction ( LVEF ) ≥ 60 %. 6.Non-surgical sterilization or women of childbearing age who are required to use a medically approved contraceptive (such as an intrauterine device, contraceptive pill or condom) during the study treatment period and for 6 months after the study treatment period ends; Female patients of childbearing age who were not surgically sterilized must have a negative serum or urine HCG test within 7 days prior to study enrollment; And must be non-lactation period; For male patients with a partner of a woman of childbearing age, effective contraceptive methods should be used during the trial period and within 6 months after the last Fluzoparib or Dalpiciclib administration.

Understand the research procedures and methods, volunteer to participate in the experiment, and sign the informed consent. And fully understand the trial content, process and possible adverse reactions.

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Exclusion Criteria:1.Plan to receive any other antitumor therapy during this trial; 2.Within 4 weeks of the first administration of the drug in this study, the patient has received radiotherapy for sarcoma, or received compound names such as Fluzoparib, Dalpiciclib, drug administration or cell therapy in other clinical trials; 3.Imaging diagnosis showed the presence of tumor lesions in the brain; 4.Active malignancies other than sarcoma within 5 years or at the same time. Cured localized tumors, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder carcinoma, prostate carcinoma in situ, cervical carcinoma in situ, breast carcinoma in situ, etc., could be included in the group.

5.Patients with clinical symptoms of ascites requiring puncture or drainage, or patients who have received ascites drainage within the past 3 months, except those who only show a small amount of ascites without clinical symptoms on imaging; Uncontrolled or medium or above pleural effusion and pericardial effusion; There is evidence of abdominal gas accumulation that cannot be explained by puncture or recent surgical procedures 6.Have a history of epilepsy, or a history of seizures within 12 months prior to the first administration of the study drug (including a history of transient ischemic attack, cerebral stroke (except imaging only found ischemic focus but no corresponding clinical history), brain trauma with disturbance of consciousness requiring hospitalization); 7.Previous treatment with PARP or CDK4/6 inhibitors, including but not limited to Fluzoparib and Dalpiciclib; 8.Allergic constitution, including severe drug allergy or drug allergic reaction history; Known allergies or intolerances to Fluzoparib, Dalpiciclib or their excipients; 9.Severe infections (CTC AE ≥grade 2), such as severe pneumonia, bacteremia, and infection complications requiring hospitalization, occurred within 4 weeks prior to the first use of the study drug; Baseline chest imaging suggests active pulmonary inflammation, signs and symptoms of infection within 2 weeks prior to the first use of the study drug, or the need for oral or intravenous use of the drug · Antibiotic therapy (excluding the use of prophylactic antibiotics); 10.Drugs that may affect P-gp should not be discontinued during the study； 11.Had use of a potent/moderate-acting drug that inhibits or induces the liver drug metabolizing enzyme CYP3A4 14 days prior to initial administration； 12.Inability to swallow, chronic diarrhea, intestinal obstruction, or other factors affecting drug administration and absorption; 13.A history of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), or other malignancies (other than carcinoma in situ with complete response and malignancies determined by the investigator to be slow in progression) within 5 years prior to the initial administration of the study; 14.Combined with other viral infection (anti-HCV, anti-HIV positive, HBsAg positive) or syphilis infection; 15.A history of immunodeficiency (including HIV test positive, other acquired or congenital immunodeficiency diseases) or a history of organ transplantation; 16.A known history of psychotropic drug abuse, alcoholism and drug use; A concomitant disease (such as poorly controlled hypertension, severe diabetes, thyroid disease, and psychosis) or any other condition that, in the investigator's judgment, seriously endangers the patient's safety or affects the patient's ability to complete the study.

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Where this trial is running

Guangzhou, Guangdong

• Cancer Center of Sun-Yat Sen University (CCSYSU) — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: [e-mail] Wang, MD — Sun Yat-sen University
• Study coordinator: Jin Wang, MD

Conditions Sarcoma; Fluzoparib; Dalpiciclib