Soft Tissue Sarcoma (STS)Phase 2SPARE-04NCT07612098
Preoperative Radiotherapy and Anlotinib With or Without Penpulimab for Soft Tissue Sarcoma
A Phase 2 study testing Anlotinib, Penpulimab and Preoperative Radiotherapy in people with Soft Tissue Sarcoma (STS), run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
Trial summary
Soft tissue sarcoma is a rare cancer that often requires surgery combined with radiotherapy. Preoperative radiotherapy can improve the chance of complete tumor removal and limb preservation, but some patients still experience local recurrence, distant metastasis, or poor tumor response. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Soft Tissue Sarcoma (STS)
- What is being tested?
- Anlotinib, Penpulimab and Preoperative Radiotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 274 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2026to 31 Dec 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Primary or recurrent soft tissue sarcoma of the extremity or trunk with intermediate- to high-grade disease and tumor size >=5 cm or deep-seated tumor, for which radiotherapy is recommended after multidisciplinary evaluation.
- Age >=15 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3.
- Histologically confirmed soft tissue sarcoma.
- At least one evaluable lesion.
- Able to tolerate radiotherapy, anlotinib, and penpulimab treatment.
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- Female participants of childbearing potential, or male participants with female partners of childbearing potential, must agree to use effective contraception during the treatment period and for 6 months after the last dose of study treatment.
- Able to provide written informed consent.
- Able and willing to comply with follow-up.
Who cannot join
- No gross tumor remaining after unplanned tumor resection performed at another hospital.
- Contraindications to targeted therapy or immunotherapy due to comorbidities, including allergy, autoimmune disease, active bleeding, ulcer, intestinal perforation, intestinal obstruction, uncontrolled hypertension, New York Heart Association class III-IV cardiac dysfunction, or severe hepatic or renal dysfunction.
- Dermatofibrosarcoma protuberans, desmoid fibromatosis, tenosynovial giant cell tumor, or other locally aggressive diseases.
- Benign tumors.
- Sarcoma subtypes for which chemotherapy is recommended as the preferred neoadjuvant treatment according to guidelines, such as embryonal rhabdomyosarcoma or Ewing sarcoma.
- Lipoma-like liposarcoma or well-differentiated liposarcoma.
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- New malignant tumor within 5 years before enrollment, except cervical carcinoma in situ, early-stage basal cell carcinoma of the skin, or early-stage lung cancer.
- Soft tissue sarcoma that can be cured by wide local excision alone.
- Prior radiotherapy to the same anatomical site.
- Other severe medical comorbidities that would preclude surgery or participation in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Shijie Yang contact
China1 site
Cancer Hospital, National Cancer Center, CAMS & PUMC
Beijing, Beijing Municipality, 100021
About this study
Official title: A Prospective Multicenter Randomized Controlled Study of Preoperative Radiotherapy Combined With Targeted Therapy With or Without Immunotherapy for Soft Tissue Sarcoma
Soft tissue sarcoma is a rare cancer that often requires surgery combined with radiotherapy. Preoperative radiotherapy can improve the chance of complete tumor removal and limb preservation, but some patients still experience local recurrence, distant metastasis, or poor tumor response.
This is a prospective, multicenter, randomized phase II study for patients with localized soft tissue sarcoma of the extremity or trunk who need preoperative radiotherapy. Participants will be randomly assigned to receive preoperative radiotherapy plus anlotinib, or preoperative radiotherapy plus anlotinib and penpulimab. Surgery will be performed after completion of neoadjuvant treatment according to the study protocol.
The main purpose of this study is to evaluate whether adding penpulimab to preoperative radiotherapy and anlotinib can improve 3-year disease-free survival. The study will also assess pathological response, wound complications, treatment-related adverse events, local control, distant metastasis-free survival, overall survival, limb function, quality of life, and exploratory biomarkers related to treatment response.
Read the detailed description
Preoperative radiotherapy is an established treatment approach for patients with localized soft tissue sarcoma of the extremity or trunk, particularly when limb preservation and complete surgical resection are important treatment goals. However, the pathological response to preoperative radiotherapy alone remains limited in some patients, and local recurrence or distant metastasis can still occur after multidisciplinary treatment.
Anlotinib is a multitarget tyrosine kinase inhibitor with antiangiogenic activity and has shown clinical activity in soft tissue sarcoma. Immune checkpoint blockade may further enhance antitumor effects when combined with radiotherapy and antiangiogenic therapy by modulating the tumor microenvironment. The optimal patient population and risk-benefit profile of this combined neoadjuvant strategy require prospective evaluation.
This study is designed to compare preoperative radiotherapy plus anlotinib with preoperative radiotherapy plus anlotinib and penpulimab in patients with localized soft tissue sarcoma who are candidates for neoadjuvant treatment followed by surgery. The study will evaluate whether the addition of penpulimab improves disease control while maintaining acceptable safety, surgical feasibility, and postoperative wound healing.
Participants will receive protocol-defined neoadjuvant treatment before surgery and will be followed after surgery for disease outcomes, safety, limb function, quality of life, and translational biomarker analyses. The study also includes collection and analysis of clinical, imaging, pathological, and molecular data to explore potential predictors of treatment response and resistance.
- Conditions
- Soft Tissue Sarcoma (STS)
- Being tested
- Anlotinib, Penpulimab, Preoperative Radiotherapy, Surgery
- Keywords
- Soft Tissue Sarcoma, Preoperative Radiotherapy, Neoadjuvant Therapy, Anlotinib, Penpulimab
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnlotinibDrug
Anlotinib will be administered orally at 12 mg once daily, starting 1 week before radiotherapy and continuing until 4 weeks after completion of radiotherapy, on a 2-weeks-on and 1-week-off schedule for 3 cycles. Dose modification will be performed according to protocol-defined toxicity management criteria.
PenpulimabDrug
Also called Anti-PD-1 Antibody
Penpulimab will be administered intravenously at 200 mg every 3 weeks, starting 1 week before radiotherapy and continuing until 4 weeks after completion of radiotherapy, for a total of 3 cycles.
Preoperative RadiotherapyRadiation
Also called Neoadjuvant Radiotherapy
Preoperative radiotherapy will be delivered according to the protocol-defined target volume and dose schedule before surgery. Radiotherapy may be given as conventional fractionation or moderate hypofractionation according to the study protocol.
SurgeryProcedure or surgery
Surgery will be performed after completion of neoadjuvant treatment. The goal of surgery is complete tumor resection while preserving organ and limb function whenever feasible, according to protocol-defined surgical principles.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Preoperative Radiotherapy Plus Anlotinib | Active comparator | Preoperative Radiotherapy Plus Anlotinib Receives: Drug: Anlotinib; Radiation: Preoperative Radiotherapy; Procedure: Surgery |
| Arm B: Preoperative Radiotherapy Plus Anlotinib and Penpulimab | Experimental | Preoperative Radiotherapy Plus Anlotinib and Penpulimab Receives: Drug: Anlotinib; Drug: Penpulimab; Radiation: Preoperative Radiotherapy; Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-Year Disease-Free Survival
Disease-free survival is defined as the time from randomization to the first occurrence of local recurrence, distant metastasis, new malignancy, or death from any cause. Participants without an event will be censored at the date of last follow-up.
Measured: From randomization to 3 years after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2026
- Study start1 Jul 2026 (estimated)
- Primary completion31 Dec 2031 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Soft Tissue Sarcoma (STS)Studies of the same condition, open and under way.
- More trials run by Cancer Institute and Hospital, Chinese Academy of Medical SciencesThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 274 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, NINGNING LU, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Investigators
- Ning-Ning Lu, Principal investigator, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07612098
- Sponsor's protocol ID
- NCC6371
- Acronym
- SPARE-04
- Status last verified
- May 2026
- First submitted
- 21 May 2026
- Last updated
- 28 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Multicenter Randomized Controlled Study of Preoperative Radiotherapy Combined With Targeted Therapy With or Without Immunotherapy for Soft Tissue Sarcoma
- ClinicalTrials.gov ID
- NCT07612098
- Acronym / sponsor ID
- SPARE-04 / NCC6371
- Conditions
- Soft Tissue Sarcoma (STS)
- Keywords
- Soft Tissue Sarcoma, Preoperative Radiotherapy, Neoadjuvant Therapy, Anlotinib, Penpulimab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 274 participants (estimated)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 1 Jul 2026 (estimated)
- Primary completion
- 31 Dec 2031 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 28 May 2026 (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.
Soft tissue sarcoma is a rare cancer that often requires surgery combined with radiotherapy. Preoperative radiotherapy can improve the chance of complete tumor removal and limb preservation, but some patients still experience local recurrence, distant metastasis, or poor tumor response.
This is a prospective, multicenter, randomized phase II study for patients with localized soft tissue sarcoma of the extremity or trunk who need preoperative radiotherapy. Participants will be randomly assigned to receive preoperative radiotherapy plus anlotinib, or preoperative radiotherapy plus anlotinib and penpulimab. Surgery will be performed after completion of neoadjuvant treatment according to the study protocol.
The main purpose of this study is to evaluate whether adding penpulimab to preoperative radiotherapy and anlotinib can improve 3-year disease-free survival. The study will also assess pathological response, wound complications, treatment-related adverse events, local control, distant metastasis-free survival, overall survival, limb function, quality of life, and exploratory biomarkers related to treatment response.
Detailed description
Preoperative radiotherapy is an established treatment approach for patients with localized soft tissue sarcoma of the extremity or trunk, particularly when limb preservation and complete surgical resection are important treatment goals. However, the pathological response to preoperative radiotherapy alone remains limited in some patients, and local recurrence or distant metastasis can still occur after multidisciplinary treatment.
Anlotinib is a multitarget tyrosine kinase inhibitor with antiangiogenic activity and has shown clinical activity in soft tissue sarcoma. Immune checkpoint blockade may further enhance antitumor effects when combined with radiotherapy and antiangiogenic therapy by modulating the tumor microenvironment. The optimal patient population and risk-benefit profile of this combined neoadjuvant strategy require prospective evaluation.
This study is designed to compare preoperative radiotherapy plus anlotinib with preoperative radiotherapy plus anlotinib and penpulimab in patients with localized soft tissue sarcoma who are candidates for neoadjuvant treatment followed by surgery. The study will evaluate whether the addition of penpulimab improves disease control while maintaining acceptable safety, surgical feasibility, and postoperative wound healing.
Participants will receive protocol-defined neoadjuvant treatment before surgery and will be followed after surgery for disease outcomes, safety, limb function, quality of life, and translational biomarker analyses. The study also includes collection and analysis of clinical, imaging, pathological, and molecular data to explore potential predictors of treatment response and resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Preoperative Radiotherapy Plus Anlotinib | Active comparator | Drug: Anlotinib, Radiation: Preoperative Radiotherapy, Procedure: SurgeryPreoperative Radiotherapy Plus Anlotinib |
| Arm B: Preoperative Radiotherapy Plus Anlotinib and Penpulimab | Experimental | Drug: Anlotinib, Drug: Penpulimab, Radiation: Preoperative Radiotherapy, Procedure: SurgeryPreoperative Radiotherapy Plus Anlotinib and Penpulimab |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Primary or recurrent soft tissue sarcoma of the extremity or trunk with intermediate- to high-grade disease and tumor size >=5 cm or deep-seated tumor, for which radiotherapy is recommended after multidisciplinary evaluation.
- Age >=15 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3.
- Histologically confirmed soft tissue sarcoma.
- At least one evaluable lesion.
Key exclusion criteria (10 listed)
- No gross tumor remaining after unplanned tumor resection performed at another hospital.
- Contraindications to targeted therapy or immunotherapy due to comorbidities, including allergy, autoimmune disease, active bleeding, ulcer, intestinal perforation, intestinal obstruction, uncontrolled hypertension, New York Heart Association class III-IV cardiac dysfunction, or severe hepatic or renal dysfunction.
- Dermatofibrosarcoma protuberans, desmoid fibromatosis, tenosynovial giant cell tumor, or other locally aggressive diseases.
- Benign tumors.
- Sarcoma subtypes for which chemotherapy is recommended as the preferred neoadjuvant treatment according to guidelines, such as embryonal rhabdomyosarcoma or Ewing sarcoma.
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 |
|---|---|---|
| AnlotinibAnlotinib will be administered orally at 12 mg once daily, starting 1 week before radiotherapy and continuing until 4 weeks after completion of radiotherapy, on a 2-weeks-on and 1-week-off schedule for 3 cycles. Dose modification will be performed according to protocol-defined toxicity management criteria. | Drug | Arm A: Preoperative Radiotherapy Plus Anlotinib, Arm B: Preoperative Radiotherapy Plus Anlotinib and Penpulimab |
| PenpulimabAlso: Anti-PD-1 AntibodyPenpulimab will be administered intravenously at 200 mg every 3 weeks, starting 1 week before radiotherapy and continuing until 4 weeks after completion of radiotherapy, for a total of 3 cycles. | Drug | Arm B: Preoperative Radiotherapy Plus Anlotinib and Penpulimab |
| Preoperative RadiotherapyAlso: Neoadjuvant RadiotherapyPreoperative radiotherapy will be delivered according to the protocol-defined target volume and dose schedule before surgery. Radiotherapy may be given as conventional fractionation or moderate hypofractionation according to the study protocol. | Radiation | Arm A: Preoperative Radiotherapy Plus Anlotinib, Arm B: Preoperative Radiotherapy Plus Anlotinib and Penpulimab |
| SurgerySurgery will be performed after completion of neoadjuvant treatment. The goal of surgery is complete tumor resection while preserving organ and limb function whenever feasible, according to protocol-defined surgical principles. | Procedure or surgery | Arm A: Preoperative Radiotherapy Plus Anlotinib, Arm B: Preoperative Radiotherapy Plus Anlotinib and Penpulimab |
Primary outcome
3-Year Disease-Free Survival
Time frame: From randomization to 3 years after randomization
Disease-free survival is defined as the time from randomization to the first occurrence of local recurrence, distant metastasis, new malignancy, or death from any cause. Participants without an event will be censored at the date of last follow-up.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
- Individual participant dataSharing planned: Undecided
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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.
Shijie Yang contact
Ning-Ning Lu principal investigator
Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
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, Penpulimab and Preoperative Radiotherapy in people with Soft Tissue Sarcoma (STS), run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences 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 9 inclusion and 10 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: opening soon, as of the sponsor's last update on 28 May 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ning-Ning Lu (+868611804268, Ning-Ning.Lu@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-Year Disease-Free Survival (time frame: From randomization to 3 years after randomization). 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 28 May 2026.