Anlotinib and Radiotherapy in Resectable Soft Tissue Sarcoma

NCT05602415 | Unknown Phase 2

• 1 other identifier: RJ2019-200
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Soft Tissue Sarcoma; High Risk of Recurrence; Anlotinib; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Local Recurrence Free Survival (LRFS)

  From the time of surgery to the time of local recurrence identified by image examination.

  36-month

Secondary Outcomes (3)

• Metastasis free survival (MFS)

  36-month

• Overall Survival (OS)

  36-month

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  an average of 3 years

Study Arms (1)

Surgery + Dose Reduced Radiotherapy + Anlotinib

EXPERIMENTAL

Surgery would be performed to resect soft tissue sarcoma with as wide margin as possible. Important vessels and nerves should be preserved. Postoperative radiotherapy would be performed. Postoperative intensity-modulated RT (IMRT) will be performed (50 Gy in 2.0 Gy per fraction). 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).

Drug: Anlotinib; Radiation: Radiotherapy; Procedure: Surgery

Interventions

Anlotinib DRUG

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.

Also known as: AL3818

Surgery + Dose Reduced Radiotherapy + Anlotinib

Radiotherapy RADIATION

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.

Surgery + Dose Reduced Radiotherapy + Anlotinib

Surgery PROCEDURE

Surgery

Surgery + Dose Reduced Radiotherapy + Anlotinib

Eligibility Criteria

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

You may qualify if:

• 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).
• Upper limb (including shoulder), lower limb (including hip) and pelvic soft-tissue sarcoma,
• Age ≥ 18 years,
• 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,
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2,
• 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,
• 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
• 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,
• Voluntary signed and dated written informed consent prior to any specific procedure,
• Patients have a life expectancy of more than 2 years with appropriate therapy,
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

You may not qualify if:

• Any previous treatment, including chemotherapy, radiotherapy and target therapy, within 6 months from the last time prior to study treatment,
• Soft-tissue sarcoma occurred at head and neck, visceral organs, retroperitoneum, peritoneum, pelvis within the confines of the bony pelvis
• Patients with the following entities were excluded: GIST, rhabdomyosarcoma, chondrosarcoma, osteosarcoma, dermatofibrosarcoma protuberans, Ewing sarcoma, primitive neuroectodermal tumor, inflammatory myofibroblastic tumor, and malignant mesothelioma.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication,
• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy,
• 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,
• 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,
• Patients with uncontrolled seizures,
• Women of childbearing potential who are not using an effective method of contraception; women who are pregnant or breast feeding,
• No prior or concurrent malignant disease diagnosed or treated in the last 2 years,
• Resting ECG with QTc \> 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome,
• Blood transfusions within 14 days prior to study start,
• Patients with myelodysplastic syndrome/acute myeloid leukaemia,
• Major surgery within 6 months of starting study treatment and patients must have recovered from any effects of any major surgery,
• Participation to a study involving a medical or therapeutic intervention in the last 3 months,

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Conditions

Sarcoma

Interventions

anlotinib; Radiotherapy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Yuhui Shen, MD

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuhui Shen, MD

CONTACT

+86 13918209875; yuhuiss@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2020
• First Posted: November 2, 2022
• Study Start: November 1, 2022
• Primary Completion: January 1, 2023
• Study Completion: May 1, 2024
• Last Updated: November 2, 2022

Record last verified: 2022-10

Locations

CN (1)