Phase Ib/II Study of Fluzoparib in Combination With Dalpiciclib in Patients With Locally Advanced or Metastatic Sarcoma

NCT05952128 | Unknown Phase 2

• 1 other identifier: B2023-085-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, single-arm phase Ib / II clinical trial, which was included with two phase. The main purpose of the phase Ib part was to determine the dose-limiting toxicity ( DLT ), maximum tolerated dose ( MTD ), and recommended dose ( RP2D ) of Fluzoparib combined with Dalpiciclib in patients with locally advanced or metastatic sarcoma. The phase II part is mainly to observe the efficacy and safety of Fluzoparib combined with Dalpiciclib.

Conditions

Sarcoma

Keywords

Fluzoparib; Dalpiciclib

Outcome Measures

Primary Outcomes (4)

• Recommended Phase II dose (RP2D)

  Determination of Recommended Phase II dose (RP2D) of Escalating Dose of Fluzoparib with Dalpiciclib.

  from 4 weeks to 20 weeks after the first dose of Fluzoparib and Dalpiciclib combination therapy

• dose limiting toxicity (DLT).

  Observe the incidence of dose limiting toxicity (DLT).

  from 4 weeks to 20 weeks after the first dose of Fluzoparib and Dalpiciclib combination therapy

• maximize toxicity dose(MTD)

  Determination of maximize toxicity dose(MTD)

  from 4 weeks to 20 weeks after the first dose of Fluzoparib and Dalpiciclib combination therapy

• Objective Response Rate(ORR) as Assessed by the Investigator according to RECIST v1.1

  Objective Response Rate(CR+PR), defined as best overall response (complete or partial response) across all assessment time points, determined using RECIST v1.1 criteria.

  up to approximately 2 Years

Secondary Outcomes (5)

• Disease control rate(DCR)

  Up to approximately 2 Years

• Duration of remisson(DoR)

  Up to approximately 2 Years

• Progression free surviral(PFS)

  Up to approximately 2 Years

• Overall survial(OS)

  Up to approximately 2 Years

• Incidence of Adverse Events [safety and tolerability]

  From the first administration to 30 days after the last administration

Study Arms (1)

Fluzoparib+ Dalpiciclib

EXPERIMENTAL

Fluzoparib in combination with Dalpiciclib

Drug: Fluzoparib+ Dalpiciclib

Interventions

Fluzoparib+ Dalpiciclib DRUG

Drug Fluzoparib 100mg bid PO qd, administered continuously until disease progression, unacceptable toxicity or death. 28 days as a treatment cycle. Other names: SHR-3162 Drug Dalpiciclib 100mg/125mg/150mg PO qd, administered only from day1 to day 21 every cycle until disease progression, unacceptable toxicity or death. 28 days as a treatment cycle. Other names: SHR-6390

Fluzoparib+ Dalpiciclib

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Jiangsu Hengrui Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Cancer Center of Sun-Yat Sen University (CCSYSU)

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Sarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• wangjinr@sysucc.org.cn Wang, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jin Wang, MD

CONTACT

020-87343910; wangjinr@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician Professor

Study Record Dates

• First Submitted: July 11, 2023
• First Posted: July 19, 2023
• Study Start: July 1, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: July 19, 2023

Record last verified: 2023-07

Locations

CN (1)