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
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.
- 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
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- 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