Trial Title:
TQB3616 Capsules in the Treatment of Dedifferentiated Liposarcoma
NCT ID:
NCT05496569
Condition:
Dedifferentiated Liposarcoma
Conditions: Official terms:
Liposarcoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
TQB3616 capsule
Description:
TQB3616 capsule is a cyclin-dependent kinase 4/6 kinase inhibitor
Arm group label:
TQB3616 capsules
Intervention type:
Drug
Intervention name:
TQB3616 placebo
Description:
Placebo
Arm group label:
TQB3616 placebo
Summary:
A clinical trial evaluating TQB3616 capsules versus placebo in the treatment of
dedifferentiated liposarcoma. Divided into 2 stages, the second stage, a total of 118
subjects are planned to be enrolled.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 1 Subjects shall voluntarily join the research, capable of giving written informed
consent with good compliance;
- 2 Age: 18-75 years old (calculated based on the time of signing the informed consent
form); The Eastern Cooperative Oncology Group performance status (ECOG PS) score:
0-1 points; Body mass index (BMI)>18.5 and body weight>40kg; Expected survival
time>3 months;
- 3 Patients with dedifferentiated liposarcoma who were diagnosed as unresectable or
refused surgery after multidisciplinary consultation, and the pathological and
imaging review results showed the presence of dedifferentiated liposarcoma
component, and the subjects must also meet any of the following categories:
1. Newly diagnosed dedifferentiated liposarcoma;
2. Patients with residual disease after surgery;
3. Local recurrence and metastatic dedifferentiated liposarcoma;
4. Patients with disease progression confirmed by imaging results within nearly 6
months; Note: Difficult to resection by surgery: （R0：Complete tumor resection
/R1：Residual tumor cells at the resection margin ）resection cannot be achieved
by surgery according to the investigator's assessment: ①The tumor is huge or
involves important organs; ②The tumor is located in an important vascular
pathway; ③The tumor has multiple metastases, It is difficult to control by
surgery; ④ Combination of serious medical diseases can cause fatal surgical
risks; ⑤ Recurrence after multiple operations is not suitable for immediate
surgery.
Treatment-naive subjects: Subjects who have not received systemic drug therapy or have
not relapsed within 6 months after postoperative adjuvant therapy.
Treatment-experienced subjects: Subjects who have relapsed within 6 months after
receiving first-line systemic drug therapy or postoperative adjuvant therapy.
- 4 According to the Response Evaluation Criteria in Solid Tumors 1.1（RECIST 1.1）
criteria, there is at least one measurable lesion. If the measurable lesion is
located in the area of previous radiotherapy, it should be clearly defined as a
progressive state;
- 5 Subjects have recovered to ≤Grade 1 or baseline (according to Common Terminology
Criteria for Adverse Events Version 5.0 [CTCAE v 5.0]), alopecia and peripheral
Grade 2 all acute toxic effects of prior treatment or surgery prior to first dose
except for neuropathy;
- 6 Adequate major organ function meeting the following criteria:
1. Routine blood tests criteria (no blood transfusion or correction with
hematopoietic stimulating factor drugs within 7 days before the examination):
1. Hemoglobin (HGB)≥90.0g/L;
2. Absolute neutrophil value (ANC)≥1.5×109/L;
3. Platelet count (PLT)≥90×109/L;
2. Biochemical examination criteria:
1. Total bilirubin (TBIL)≤1.5 times the upper limit of normal (ULN); Gilbert
syndrome patients≤3×ULN;
2. Amino acid aminotransferase (ALT) and aspartate aminotransferase
(AST)≤3×ULN. If accompanied by liver metastasis, ALT and AST≤5×ULN;
3. Serum creatinine (CR)≤178μmol/L or creatinine clearance rate
(CCR)>50ml/min;
3. Urine routine examination criteria: Urine routine indicates urine protein<++;
if urine protein≥++, the 24-hour urine protein quantification should be
confirmed≤1.0 g;
4. Coagulation function criteria: Prothrombin time (PT), activated partial
thromboplastin time (APTT), international normalized ratio (INR)≤1.5×ULN (no
anticoagulation therapy);
5. Echocardiography assessment: Left ventricular ejection fraction (LVEF)≥50%;
6. 12-lead Electrocardiogram（ECG）assessment: QTc<450ms (male), QTc<470ms (female).
- 7 Female subjects of childbearing age shall agree to use contraceptive measures
(such as intrauterine devices, contraceptives or condoms) during the study period
and within 6 months after the end of the study; serum pregnancy test negative within
7 days before study enrollment , and must be non-lactating subjects; male subjects
shall agree to use contraception during the study period and for 6 months after the
end of the study period.
Exclusion Criteria:
- 1 Tumor disease and medical history:
1. Subjects with atypical lipomatous tumor/well-differentiated liposarcoma,
myxoid/round cell liposarcoma, pleomorphic liposarcoma on pathology and imaging
review;
2. Have developed or currently suffers from other malignant tumors within past 3
years. The following two conditions were eligible for enrollment: Other
malignancies treated with single surgery, achieving 5 consecutive years of
disease-free survival (DFS); Cured cervical carcinoma in situ, non-melanoma
skin cancer, and superficial bladder tumors [Ta (non-invasive tumor), Tis
(carcinoma in situ), and T1 (tumor-infiltrating basement membrane)]; Patients
with other sources of carcinoma in situ and patients with previous malignancies
who are currently in remission will be eligible to participate in the study if
the investigator determines that the likelihood of recurrence is very low and
will require sponsor approval prior to enrollment of these patients;
3. Severe bone damage caused by tumor bone metastasis; including pathological
fractures of weight-bearing bones (such as vertebrae, pelvis, femur, tibia,
phalanges, calcaneus, etc.) and spinal cord compression that occurred within 6
months or that the investigators judged to be likely to occur in the near
future;
4. Imaging Computed Tomography or Magnetic Resonance Imaging (CT or MRI) shows the
presence of tumor thrombus, brain metastasis or the number of lesions > 10;
5. Uncontrolled pleural effusion, pericardial effusion or ascites that still needs
repeated drainage (judgment by the investigator).
- 2 Previous anti-tumor or concomitant drug therapy:
1. Received chemotherapy (including anthracyclines), radiotherapy, major surgery,
biological therapy, cytokine immunotherapy, hormone therapy, clinical trial
drug therapy, traditional Chinese medicine with anti-tumor indications or
Chinese patent medicine, etc.
2. Received major surgery, major surgical treatment, incisional biopsy, obvious
traumatic injury within 4 weeks before the first treatment with the study drug,
or has not been able to fully recover from the previous surgery as judged by
the investigator, and has anti-tumor indications Chinese medicine or
proprietary Chinese medicine, etc.;
3. Previously received Abemaciclib or Palbociclib and any other CDK4/6 inhibitor
treatment;
4. The target drug (or anti- programmeddeath-1/ Programmed cell death 1 ligand 1
and other immune drugs) is not used for at least 5 half-lives (calculated from
the end of the last treatment) from the time of first receiving the study drug
to the last time. If it is a combination drug, calculated based on the drug
with the longest half-life;
5. After receiving the study drug for the first time subjects who have used drugs
or traditional chinese medicines containing strong Cytochrome P450 3A4(CYP3A4)
inhibitors or inducers (such as Carbamazepine, Phenobarbital, Pioglitazone,
etc.) within the first 4 weeks and cannot be stopped during the treatment
period;
- 3 Comorbid diseases and medical history:
1. Liver abnormalities:
1. Decompensated cirrhosis (Child-Pugh liver function Grade B or C);
2. Active or chronic hepatitis (Hepatitis B reference: Hepatitis B Surface
Antigen (HBsAg) positive, Hepatitis B Virus DeoxyriboNucleic Acid
(HBV-DNA)>1000 copies/mL or>200IU/mL; Hepatitis C reference: Hepatitis C
virus (HCV )antibody positive, and the HCV virus titer detection value
exceeds the upper limit of the normal value); HBV surface antigen positive
or core antibody positive, HCV antibody positive subjects who meet the
entry conditions, after antiviral treatment subjects who meet the above
criteria can be admitted into the group, and antiviral drugs can be used
to prevent virus activation during the group period.
3. Patients with ascites or bleeding diseases secondary to hepatic
insufficiency.
2. Renal abnormalities: renal failure requiring hemodialysis or peritoneal
dialysis;
3. Cardiovascular and cerebrovascular abnormalities:
1. Patients with a history of epilepsy, or a history of seizures, disturbance
of consciousness or transient ischemic attack within the last 12 months,
or a history of unexplained coma;
2. New York Heart Association Grade II to IV heart failure as defined by
grade. Second degree or higher heart block, myocardial infarction or
arterial thrombosis event, unstable arrhythmia or unstable angina pectoris
within the past 6 months;
3. Cerebrovascular accident, cerebral infarction, etc. occurred within 6
months;
4. Hypertension uncontrolled by drugs (systolic blood pressure≥150mmHg,
diastolic blood pressure≥100mmHg); For patients with a history of
hypertension, if blood pressure is well controlled by antihypertensive
therapy, they are allowed to participate in this study;
5. Past or current heart valve inflammation, endocarditis;
6. Cardiovascular syncope, pathological ventricular arrhythmia (including but
not limited to ventricular tachycardia and ventricular fibrillation) or
sudden cardiac death. Atrial fibrillation or other cardiac arrhythmia
requiring medication.
4. Gastrointestinal tract abnormalities:
1. Inability to take oral medication (such as inability to swallow, chronic
diarrhea, intestinal obstruction, etc.);
2. History of malabsorption syndrome or other diseases that interfere with
gastrointestinal absorption;
3. Cerebrovascular accident, cerebral infarction, etc. occurred within 6
months;
4. Chronic diarrhea of Grade 2 or above persists despite the maximum medical
treatment;
5. The investigator judged that it may cause gastrointestinal bleeding and
perforation other conditions.
5. Immunodeficiency history:
1. Known human immunodeficiency virus (HIV) infection;
2. Other acquired and congenital immunodeficiency diseases;
3. Prepared or previously received organ transplantation, or received within
60 days before the first dose Hematopoietic stem cell transplantation, or
with obvious host transplantation response (except corneal
transplantation);
4. Systemic or topical immunosuppressive or hormonal therapy is required to
achieve immunosuppression, and glucocorticoids must continue to be used
within 7 days before the first dose Hormones, or patients who still need
to use immunosuppressive drugs within 5 half-lives before the first dose
(daily dose of glucocorticoid <7.5 mg prednisone or other equivalent
therapeutic hormones, autoimmune-related diseases judged by the
investigator to be in stable phase) except patients).
Note: Hormone replacement therapy (e.g., Tthyroxine, Insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency) is
not considered systemic therapy and is permitted.
6. Bleeding risk:
1. Suffering from bleeding (hemoptysis), coagulation disease, or using
Warfarin, Aspirin and other antiplatelet agglutination drugs (except
Aspirin ≤100 mg/d for prophylaxis);
2. Regardless of severity, with any signs or history of bleeding
constitution;
3. Any CTCAE ≥ Grade 3 bleeding or bleeding events within 4 weeks prior to
the first dose.
7. The patients have an active systemic infection (such as a bacterial infection
requiring intravenous antibiotic therapy at the start of study treatment, a
fungal infection, or a detectable viral infection requiring systemic therapy)
or an excessive viral load.
8. History of idiopathic pulmonary fibrosis, history of organized pneumonia (e.g.,
bronchiolitis obliterans), history of drug-induced pneumonia, history of
idiopathic pneumonia, or evidence of active pneumonia on chest CT scan during
screening.
9. There is a clear history of neurological or psychiatric disorders in the past.
10. Combined with severe or uncontrolled diseases, the investigators judge that
there may be a greater risk of entering this study, including but not limited
to:
1. Type 1 or type 2 diabetes that cannot be controlled by drugs (or fasting
blood glucose (FBG) > 10mmol/L);
2. Thyroid disease;
3. Treponema pallidum specific antibody positive.
11. Pituitary or adrenal dysfunction history.
12. Received major surgical treatment, incisional biopsy or significant traumatic
injury within 4 weeks prior to the start of study treatment.
13. Long-term unhealed wounds or fractures.
14. Subjects who have a drug abuse history and cannot quit or have a drug use
history.
- 4 Study treatment related:
1. Have a severe allergic disease, drug allergy history, or known allergy to the
components of TQB3616 capsule and its adjuvants and similar drugs;
2. Active autoimmune disease requiring systemic therapy (such as the use of
disease-modifying drugs, corticosteroids, or immunosuppressive drugs) within 2
years prior to the start of study treatment (including but not limited to:
autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis;
asthma requiring bronchodilator medical intervention is not included);
- 5 Subjects judged by the investigator to have the possibility of recent rapid
progress, need to receive chemotherapy or lack of compliance;
- 6 According to the judgment of the investigator, there are concomitant diseases that
seriously endanger the safety of the subjects or affect the completion of the study,
or there are subjects who are not suitable for enrollment for other reasons.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Peking University First Hospital
Address:
City:
Beijing
Zip:
100034
Country:
China
Contact:
Last name:
Shikai Wu, Doctor
Phone:
15810037307
Email:
skywu4923@sina.com
Facility:
Name:
Peking University People's Hospital
Address:
City:
Beijing
Zip:
100044
Country:
China
Contact:
Last name:
Wei Guo, Doctor
Phone:
13701195504
Email:
bonetumor@163.com
Facility:
Name:
Zhongshan Hospital Fudan University
Address:
City:
Shanghai
Zip:
200032
Country:
China
Contact:
Last name:
Yuhong Zhou, Doctor
Phone:
02164041990
Email:
Zhou.yuhong@zshospital.sh.cn
Start date:
December 2022
Completion date:
December 2024
Lead sponsor:
Agency:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Agency class:
Industry
Source:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05496569
