Trial Title:
A Single-arm, Open-label, Single-center Prospective Study of Fruquintinib Combined With Envafolimab in the Treatment of Advanced or Unresectable Locally Advanced Bone and Soft Tissue Sarcoma
NCT ID:
NCT05941325
Condition:
Advanced or Unresectable Locally Advanced Bone and Soft Tissue Sarcoma
Conditions: Official terms:
Sarcoma
Conditions: Keywords:
fruquintinib
envafolimab
advanced or unresectable locally advanced bone and soft tissue sarcoma
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:
fruquintinib
Description:
VEGF receptor tyrosine-kinase inhibitor：fruquintinib（4mg), Oral，qd, d1-d14, Q3w，Until
disease progression or intolerable toxicity occurs.
Arm group label:
fruquintinib combined with envafolimab
Intervention type:
Drug
Intervention name:
Envafolimab
Description:
anti-PD-1 immune checkpoint inhibitor：Envafolimab（400mg), subcutaneous injection, d1,
Q3w，Until disease progression or intolerable toxicity occurs.
Arm group label:
fruquintinib combined with envafolimab
Summary:
Many osteosarcomas are cured with a variety of combined chemotherapy and surgery, but a
significant number will still relapse.VEGF promotes an immunosuppressive microenvironment
and contributes to immune checkpoint inhibitor resistance in cancer.We aimed to explore
the efficacy and safety of fruquintinib combined immunotherapy for bone and soft tissue
sarcoma.
Detailed description:
A single-arm, open-label, single-center prospective study of fruquintinib combined with
envafolimab in the treatment of advanced or unresectable locally advanced bone and soft
tissue sarcoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- The subjects who volunteered to join the study signed the informed consent form,
which showed good compliance and cooperated with the follow-up;
- 12-70 years old (boundary values included);
- Advanced or locally advanced bone and soft tissue sarcomas confirmed by histology or
cytology, including but not limited to leiomyosarcomas, undifferentiated pleomorphic
sarcomas, liposarcomas, synovial sarcomas, etc.;
- Patients with alveolar soft-tissue sarcoma, clear cell sarcoma, and other bone and
soft-tissue sarcomas that progressed or recurred after at least previous
anthracycline-containing chemotherapy regimens. Patients with bone and soft-tissue
sarcoma who had not received previous first-line therapy were ineligible for
chemotherapy or refused chemotherapy;
- At least one measurable lesion (RECIST 1.1);
- Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1 (amputation
patients 0-2);
- Life expectancy > 12 weeks；
- Hematologic examination (no blood transfusion within 14 days):
1. Neutrophil absolute value ≥1.5×109/L, platelet ≥100×109/L, hemoglobin
concentration ≥9g/dL;
2. Liver function (aspartate aminotransferase and glutamate aminotransferase
≤2.5×ULN, bilirubin ≤1.5×ULN; AST and ALT≤5×ULN if liver metastasis is
present);
3. Renal function (serum creatinine ≤1.5×ULN, or creatinine clearance rate
(CCr)≥60ml/min);
4. Coagulation, international standardized ratio (INR) ≤1.5, prothrombin time (PT)
and activated partial thrombin time (APTT) ≤1.5×ULN;
5. Thyroid function, thyroid stimulating hormone (TSH) ≤ the upper normal value
(ULN); If abnormal, T3 and T4 levels should be examined, and if T3 and T4
levels are normal, they can be selected;
- Women of childbearing age must have taken a serum pregnancy test negative within 7
days prior to treatment and be willing to use medically approved effective
contraception (e.g., an intrauterine device, contraceptive or condom) during the
study period and for 3 months after the last study drug use; For male subjects whose
partner is a woman of reproductive age, surgical sterilization is required or
effective contraceptive methods are recommended during the study period and for 3
months after the last study treatment;
- The parents/guardians of the young patients have the ability to understand, agree
to, and sign the study informed consent (ICF) prior to initiating any
program-related procedures; Subject may give consent with parental/guardian consent
(if applicable).
Exclusion Criteria:
- Had received radiotherapy for cancer, surgery, chemotherapy, immunotherapy, and
other investigational drugs within 4 weeks prior to treatment;
- Previous treatment with anti-PD-1 or PD-L1 combined with anti-angiogenesis TKI;
- For soft tissue sarcomas, surgical and/or radiotherapy > 5% of the bone marrow area
is planned during the study period;
- Had present central nervous system (CNS) metastases or prior brain metastases；
- Use of immunosuppressive drugs within 14 days prior to initiation of treatment,
excluding transnasal and inhaled corticosteroids or physiological doses of systemic
steroids (i.e., prednisolone dose not exceeding 10 mg per day or the physiological
equivalent of other corticosteroids);
- History of any active autoimmune disease or autoimmune disease (including but not
limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis,
hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism;
Subjects with vitiligo or asthma may have complete remission in childhood and do not
currently require medical intervention or history of allogeneic organ
transplantation or allogeneic hematopoietic stem cell transplantation);
- Severe infection (e.g., intravenous infusion of antibiotics, antifungals or
antivirals) within 4 weeks prior to treatment, or unexplained fever >38.5 ℃ during
screening/initial administration;
- Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood
pressure ≥90 mmHg, despite optimal drug treatment);
- Significant clinical bleeding symptoms or significant bleeding tendency within 3
months prior to treatment (>30 ml within 3 months, appeared hematemesis, black dung,
hematochezia) or hemoptysis (>5 mL of fresh blood within 4 weeks) , etc. Or
treatment for venous/venous thrombosis events within the previous 6 months, such as
cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage,
cerebral infarction), deep vein thrombosis, and pulmonary embolism; Or long-term
anticoagulant therapy with warfarin or heparin, or long-term antiplatelet therapy
(aspirin ≥300 mg/day or clopidogrel ≥75 mg/day);
- Active heart disease, including myocardial infarction, severe/unstable angina within
6 months prior to treatment. Echocardiographic examination of left ventricular
ejection fraction < 50%, poor arrhythmia control (including QTcF interval, men > 450
ms, female > 470 ms);
- Had other malignancies within the past 3 years or at the same time (except cured
basal cell carcinoma of the skin and carcinoma in situ of the cervix);
- Known to be allergic to the study drug or any of its excipients, or had severe
allergic reactions to other monoclonal antibodies;
- Active or uncontrolled severe infection:
1. Known human immunodeficiency virus (HIV) infection;
2. A known history of clinically significant liver disease, including viral
hepatitis [a known hepatitis B virus (HBV) carrier must exclude active HBV
infection, i.e., positive HBV DNA (> 1×104 copies /mL or > 2000 IU/ mL);
3. Known hepatitis C virus infection (HCV) with HCV RNA positive (> 1×103 copies
/mL), or other hepatitis, cirrhosis];
- Have any other disease, metabolic disorder, physical examination anomaly, abnormal
laboratory result, or any other conditions which, according to judgement of the
investigator, renders the patient inappropriate for using the investigational
product or affect interpretation of study results;
- Urine routine indicates urinary protein ≥ ++, and the 24-hour urine protein
quantification is greater than 1.0 g.
Gender:
All
Minimum age:
12 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Shanghai No.6 People Hospital
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Shuier Zheng, Doctor
Phone:
18501611082
Email:
zse78106@qq.com
Start date:
April 1, 2023
Completion date:
December 1, 2026
Lead sponsor:
Agency:
Shanghai 6th People's Hospital
Agency class:
Other
Source:
Shanghai 6th People's Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05941325
