Soft Tissue SarcomaPhase 2NCT05602415
Anlotinib and Radiotherapy in Resectable Soft Tissue Sarcoma
A Phase 2 study testing Anlotinib, Radiotherapy and Surgery in people with Soft Tissue Sarcoma and High Risk of Recurrence, run by Ruijin Hospital at 1 site in China.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Soft Tissue Sarcoma, High Risk of Recurrence, Anlotinib
- What is being tested?
- Anlotinib, Radiotherapy and Surgery
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteChina
- Study dates
- Nov 2022to May 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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,
Show all 12Show fewer
- 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.
Who cannot join
- 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,
Show all 19Show fewer
- 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,
- Patient unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons,
- Previous enrollment in the present study,
- Patients with a known hypersensitivity to study medicines or any of the excipients of the product,
- Patients with metastasis.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Ruijin Hospital Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200025
Yuhui Shen, MD, +86 13918209875
About this study
Official title: A Phase II Study of Postoperative Radiotherapy With Tyrosine Kinase Inhibitor (Anlotinib) for Resectable Soft Tissue Sarcoma With High Recurrence Risk
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
Read the 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).
- Conditions
- Soft Tissue Sarcoma, High Risk of Recurrence, Anlotinib, Radiotherapy
- Being tested
- Anlotinib, Radiotherapy, Surgery
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnlotinibDrug
Also called AL3818
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.
RadiotherapyRadiation
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.
SurgeryProcedure or surgery
Surgery
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Anlotinib; Radiation: Radiotherapy; Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Local Recurrence Free Survival (LRFS)
From the time of surgery to the time of local recurrence identified by image examination.
Measured: 36-month
Secondary outcomes (3)
Metastasis free survival (MFS)
From the time of surgery to the time of metastasis identified by image examination.
Measured: 36-month
Overall Survival (OS)
From the time of surgery to the time of death.
Measured: 36-month
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
The occurrence of each adverse events(AEs), severe AEs(SAEs) and death according the CTCAE_5.0
Measured: an average of 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2022
- Study startNov 2022 (estimated)
- Primary completionJan 2023 (estimated)
- Study completionMay 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Soft Tissue SarcomaStudies of the same condition, open and under way.
- More trials run by Ruijin HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yuhui Shen, MD, Principal investigator, Ruijin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05602415
- Sponsor's protocol ID
- RJ2019-200
- Status last verified
- Oct 2022
- First submitted
- 21 Jan 2020
- Last updated
- 2 Nov 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Postoperative Radiotherapy With Tyrosine Kinase Inhibitor (Anlotinib) for Resectable Soft Tissue Sarcoma With High Recurrence Risk
- ClinicalTrials.gov ID
- NCT05602415
- Acronym / sponsor ID
- RJ2019-200
- Conditions
- Soft Tissue Sarcoma, High Risk of Recurrence, Anlotinib, Radiotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Study start
- Nov 2022 (estimated)
- Primary completion
- Jan 2023 (estimated)
- Study completion
- May 2024 (estimated)
- First posted
- 2 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Surgery + Dose Reduced Radiotherapy + Anlotinib | Experimental | Drug: Anlotinib, Radiation: Radiotherapy, Procedure: SurgerySurgery 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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,
Key exclusion criteria (19 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AnlotinibAlso: AL3818Anlotinib 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. | Drug | Surgery + Dose Reduced Radiotherapy + Anlotinib |
| RadiotherapyPostoperative 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. | Radiation | Surgery + Dose Reduced Radiotherapy + Anlotinib |
| SurgerySurgery | Procedure or surgery | Surgery + Dose Reduced Radiotherapy + Anlotinib |
Primary outcome
Local Recurrence Free Survival (LRFS)
Time frame: 36-month
From the time of surgery to the time of local recurrence identified by image examination.
3 secondary outcomes
Metastasis free survival (MFS)
Time frame: 36-month
Overall Survival (OS)
Time frame: 36-month
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: an average of 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2022.
Related trials for Soft Tissue Sarcoma
Not yet recruiting
Molecular Subtype-Guided Postoperative Radiotherapy for Phyllodes Tumor of the Breast
Radiotherapy, Adjuvant, Phyllodes Breast Tumor
RecruitingPhase 2
Zemetostat With Anlotinib in Patients With Recurrent/Metastatic Head and Neck Soft Tissue Sarcoma
Soft Tissue Sarcoma
Active, not recruitingPhase 2
Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma
Synovial Sarcoma, Myxoid Liposarcoma
Active, not recruitingObservational study
Genomic Structural Variation in Cancer Susceptibility
Breast Cancer, Colon Cancer
RecruitingPhase 1
Anti-GD2 ADC M3554 in Advanced Solid Tumors
Advanced Solid Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yuhui Shen, MD principal investigator
Ruijin Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anlotinib, Radiotherapy and Surgery in people with Soft Tissue Sarcoma and High Risk of Recurrence, run by Ruijin Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yuhui Shen, MD (+86 13918209875, yuhuiss@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local Recurrence Free Survival (LRFS) (time frame: 36-month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2022.