Preoperative Radiotherapy and Anlotinib With or Without Penpulimab for Soft Tissue Sarcoma

NCT07612098 | Not Yet Recruiting Phase 2

• 1 other identifier: NCC6371
• Study Type: interventional
• Target: 274
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Soft Tissue Sarcoma (STS)

Keywords

Soft Tissue Sarcoma; Preoperative Radiotherapy; Neoadjuvant Therapy; Anlotinib; Penpulimab

Outcome Measures

Primary Outcomes (1)

• 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.

  From randomization to 3 years after randomization

Study Arms (2)

Arm A: Preoperative Radiotherapy Plus Anlotinib

ACTIVE COMPARATOR

Preoperative Radiotherapy Plus Anlotinib

Drug: Anlotinib; Radiation: Preoperative Radiotherapy; Procedure: Surgery

Arm B: Preoperative Radiotherapy Plus Anlotinib and Penpulimab

EXPERIMENTAL

Preoperative Radiotherapy Plus Anlotinib and Penpulimab

Drug: Anlotinib; Drug: Penpulimab; Radiation: Preoperative Radiotherapy; Procedure: Surgery

Interventions

Anlotinib DRUG

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.

Arm A: Preoperative Radiotherapy Plus Anlotinib; Arm B: Preoperative Radiotherapy Plus Anlotinib and Penpulimab

Penpulimab DRUG

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.

Also known as: Anti-PD-1 Antibody

Arm B: Preoperative Radiotherapy Plus Anlotinib and Penpulimab

Preoperative Radiotherapy RADIATION

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.

Also known as: Neoadjuvant Radiotherapy

Arm A: Preoperative Radiotherapy Plus Anlotinib; Arm B: Preoperative Radiotherapy Plus Anlotinib and Penpulimab

Surgery PROCEDURE

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.

Arm A: Preoperative Radiotherapy Plus Anlotinib; Arm B: Preoperative Radiotherapy Plus Anlotinib and Penpulimab

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

Cancer Hospital, National Cancer Center, CAMS & PUMC

Beijing, Beijing Municipality, 100021, China

Location

MeSH Terms

Conditions

Sarcoma

Interventions

anlotinib; penpulimab; spartalizumab; Neoadjuvant Therapy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Ning-Ning Lu

  Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ning-Ning Lu

CONTACT

+868611804268; Ning-Ning.Lu@hotmail.com

Shijie Yang

CONTACT

ysj14@mails.tsinghua.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Department of Radiation Oncology

Study Record Dates

• First Submitted: May 21, 2026
• First Posted: May 28, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2031
• Last Updated: May 28, 2026

Record last verified: 2026-05

Locations

CN (1)