Trial Title:
Anlotinib and Radiotherapy in Resectable Soft Tissue Sarcoma
NCT ID:
NCT05602415
Condition:
Soft Tissue Sarcoma
High Risk of Recurrence
Anlotinib
Radiotherapy
Conditions: Official terms:
Sarcoma
Recurrence
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Unknown status
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Anlotinib
Description:
Anlotinib of 12mg will be administered orally, once daily, 2-days on/1-day off, until
disease progression according to RECIST 1.1, death, unacceptable toxicity, or withdrawal
of consent for any reasons. A cycle was considered to be 3 weeks. Anlotinib should be
started 3-4 weeks after surgery, and continued for 3 months (4 cycles). The dose could be
reduced to 8-10 mg once daily for patients who had grade 3 or 4 treatment-related
toxicities, or for patients with intolerable grade 2 toxicity, despite maximum supportive
care measures. If dose reduction was necessary, then the dose of anlotinib was reduced to
10 mg once daily. If further dose reduction was necessary, the dosage was reduced to 8 mg
once daily. If the dosage of 8 mg once daily was not tolerable, then the patient stopped
receiving anlotinib.
Arm group label:
Surgery + Dose Reduced Radiotherapy + Anlotinib
Other name:
AL3818
Intervention type:
Radiation
Intervention name:
Radiotherapy
Description:
Postoperative radiotherapy would be performed. Postoperative intensity-modu¬lated RT
(IMRT) will be performed (50 Gy in 2.0 Gy per fraction). No boost dose would be added if
the margin was negative, a boost dose of 10-16 Gy would be added if the margin was
microscopically positive, and a boost dose of 16-18 would be added if the margin was
gross positive.
Arm group label:
Surgery + Dose Reduced Radiotherapy + Anlotinib
Intervention type:
Procedure
Intervention name:
Surgery
Description:
Surgery
Arm group label:
Surgery + Dose Reduced Radiotherapy + Anlotinib
Summary:
The purpose of this study is to evaluate the efficacy and safety of dose reduced
postoperative radiotherapy combined with Anlotinib for patients of soft tissue sarcoma
Detailed description:
Right now, resection and radiotherapy (RT) is the most effective and recommended
treatment for soft tissue sarcoma (STS). Local recurrence rate has significantly reduced
since the application of RT. However, RT has brought a lot of complications which had
disturbed patients' quality of life. Anlotinib is a novel tyrosine kinase inhibitor
targeting multiple factors involving tumor proliferation, vasculature, and tumor
microenvironment. Anlotinib inhibits VEGF/VEGFR signaling by selectively targeting
VEGFR-2,-3 and FGFR-1,-2,-3,-4 with high affinity. Anlotinib also suppresses the activity
of PDGFRα/β, c-Kit, Ret, Aurora-B, c-FMS, and discoidin domain receptor 1 (DDR1), leading
to significant inhibition of tumor proliferation. In phase I study, anlotinib showed
promising antitumor potential against STS. In a phase II study, anlotinib showed
antitumor activity in several STS with well tolerant and manageable adverse effect.
In this clinical study, investigators will explore the efficacy of Anlotinib combined
with dose reduced postoperative radiotherapy on recurrence and metastasis control of STS.
Patients with STS would receive standard treatment and recommended dose of radiotherapy.
In addition, they will receive anotinib from 3 or 4 weeks after surgery, and continue for
3 months. The primary endpoint is Local Recurrence Free Survival (LRFS).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Diagnosed and histopathologically confirmed as high histologic grade soft-tissue
sarcoma, including undifferentiated pleomorphic sarcoma (UPS), liposarcoma(LPS),
leiomyosarcoma (LMS), synovial sarcoma (SS), alveolar soft-part sarcoma (ASPS),
clear cell sarcoma (CCS).
2. Upper limb (including shoulder), lower limb (including hip) and pelvic soft-tissue
sarcoma,
3. Age ≥ 18 years,
4. High risk of local recurrence was defined if the largest diameter of tumor >5cm and
had at least one of below characters (1) Tumor border close (<5mm) to vital tissue
(vessel and nerve) from diagnostic MRI (2) MRI shows infiltrative tumor grow type
('focal-type' and 'diffuse-type') (3) Positive microscopic margins or macroscopic
residual (4) Recurrent tumor form previous treatment High risk of recurrence must be
assessed by staff including a surgeon specialized in sarcoma,
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2,
6. Only one lesion, and can be accurately measured at baseline as ≥ 5cm in the longest
diameter with magnetic resonance imaging (MRI) and which is suitable for accurate
repeated measurements according to RECIST 1.1,
7. Adequate hematological, renal, metabolic and hepatic function:
Haemoglobin ≥ 9 g/dL and no blood transfusions in the 14 days prior to study entry
Absolute neutrophil count (ANc) ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L Total
bilirubin ≤ 1.5 x upper limit of normality (ULN), Alanine aminotransferase (ALAT) or
aspartate aminotransferase (ASAT) ≤ 2.5 x ULN, Serum creatinine ≤ 150 μmol/L or
creatinine clearance ≥ 50 mL/min (according to local institution) in case of serum
creatinine > 150 μmol/L, TP, INR ≤ 1.5 x ULN
8. Patient is willing and able to comply with the protocol for the duration of the
study including undergoing treatment and scheduled visits and examinations including
follow up,
9. Voluntary signed and dated written informed consent prior to any specific procedure,
10. Patients have a life expectancy of more than 2 years with appropriate therapy,
11. All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.
Exclusion Criteria:
1. Any previous treatment, including chemotherapy, radiotherapy and target therapy,
within 6 months from the last time prior to study treatment,
2. Soft-tissue sarcoma occurred at head and neck, visceral organs, retroperitoneum,
peritoneum, pelvis within the confines of the bony pelvis
3. Patients with the following entities were excluded: GIST, rhabdomyosarcoma,
chondrosarcoma, osteosarcoma, dermatofibrosarcoma protuberans, Ewing sarcoma,
primitive neuroectodermal tumor, inflammatory myofibroblastic tumor, and malignant
mesothelioma.
4. Patients unable to swallow orally administered medication and patients with
gastrointestinal disorders likely to interfere with absorption of the study
medication,
5. Immunocompromised patients, e.g., patients who are known to be serologically
positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy,
6. Patients with known active hepatic disease (i.e., Hepatitis B or C) due to risk of
transmitting the infection through blood or other body fluids,
7. Patients considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection. Examples
include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within
3 months) myocardial infarction, unstable spinal cord compression (untreated and
unstable for at least 28 days prior to study entry), superior vena cava syndrome,
extensive bilateral lung disease on HRCT scan or any psychiatric disorder that
prohibits obtaining informed consent,
8. Patients with uncontrolled seizures,
9. Women of childbearing potential who are not using an effective method of
contraception; women who are pregnant or breast feeding,
10. No prior or concurrent malignant disease diagnosed or treated in the last 2 years,
11. Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or
family history of long QT syndrome,
12. Blood transfusions within 14 days prior to study start,
13. Patients with myelodysplastic syndrome/acute myeloid leukaemia,
14. Major surgery within 6 months of starting study treatment and patients must have
recovered from any effects of any major surgery,
15. Participation to a study involving a medical or therapeutic intervention in the last
3 months,
16. Patient unable to follow and comply with the study procedures because of any
geographical, familial, social or psychological reasons,
17. Previous enrollment in the present study,
18. Patients with a known hypersensitivity to study medicines or any of the excipients
of the product,
19. Patients with metastasis.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ruijin Hospital Shanghai Jiao Tong University School of Medicine
Address:
City:
Shanghai
Zip:
200025
Country:
China
Status:
Recruiting
Contact:
Last name:
Yuhui Shen, MD
Phone:
+86 13918209875
Start date:
November 2022
Completion date:
May 2024
Lead sponsor:
Agency:
Ruijin Hospital
Agency class:
Other
Source:
Ruijin Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05602415
