Trial Title:
Phase Ib/II Study of Fluzoparib in Combination With Dalpiciclib in Patients With Locally Advanced or Metastatic Sarcoma
NCT ID:
NCT05952128
Condition:
Sarcoma
Conditions: Official terms:
Sarcoma
Fluzoparib
Conditions: Keywords:
Fluzoparib
Dalpiciclib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fluzoparib+ Dalpiciclib
Description:
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
Arm group label:
Fluzoparib+ Dalpiciclib
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.
Detailed description:
The overall prognosis for patients with soft tissue sarcoma is not ideal, with a median
survival rate of only about 20 months for patients diagnosed with metastasis. Soft tissue
sarcomas (more than 50%) are deficient in HRR due to the presence of BRCA mutations in
the tumor. When patients with BRCA1/2 gene mutation are treated with PARP inhibitors, a
damage to DNA single strand breaks can be observed, and cannot be repaired promptly,
resulting in tumor cell death. In addition, selective inhibition of CDK4/6 was found to
inhibit the growth of sarcoma cells and induce their apoptosis. For example, inhibition
of CDK4 decrease the proliferation of osteosarcoma cells and promote their apoptosis in
vitro, and targeted CDK6 inhibition can inhibit the proliferation, invasion and migration
of Ewing's sarcoma cells. Therefore, in this study, Dalpicicli, a CDK4/6 inhibitor, and
Fluzoparib, a PARP inhibitor, were used in the treatment of advanced and metastatic soft
tissue sarcoma, so as to explore the efficacy and safety of the combined regimen.
Criteria for 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.
- 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.
-
Gender:
All
Minimum age:
12 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Cancer Center of Sun-Yat Sen University (CCSYSU)
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Jin Wang, MD
Phone:
020-87343910
Email:
wangjinr@sysucc.org.cn
Start date:
July 1, 2023
Completion date:
December 1, 2025
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Collaborator:
Agency:
Jiangsu Hengrui Pharmaceutical Co., Ltd.
Agency class:
Industry
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05952128
