Neoadjuvant Chemotherapy Combined With Targeted Treatment in High-risk Retroperitoneal Sarcoma

Phase 4

• Conditions: Retroperitoneal Sarcoma
• Interventions: Drug: Doxorubicin+Ifosfamide+Anlotinib(AI+A); Procedure: Radical Surgery

• Registration Number: NCT05844813
• Lead Sponsor: Peking University International Hospital

Brief Summary

The goal of this clinical trial is to explore the potential survival benefits of neoadjuvant chemotherapy combined with target treatments followed by radical surgery in patients with primary high-risk/grade retroperitoneal sarcoma.

The main questions it aims to answer are:

* Whether the 1,3-year progression-free survival time(PFS) is prolonged in the neoadjuvant therapy group, compared with the surgery-only group.

* The Overall survival time in the two groups.

* The safety and tolerance in the neoadjuvant therapy group.

Participants will be allocated into two groups once they meet the inclusion criteria.

* Surgery-only Group: Patients will directly undergo surgeries after the confirmation of diagnosis through pre-operative biopsy.

* Neoadjuvant therapy group: Patients will receive the neoadjuvant chemotherapy combined with target treatment for three circles before the following sarcoma resectional surgeries.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-11-01
• Study First Submitted: 2023-04-16
• Study First Submitted QC: 2023-04-25
• Status Verified: 2023-05
• Study First Posted: 2023-05-06
• Last Update Submitted: 2023-05-11
• Last Update Posted: 2023-05-12
• Primary Completion: 2025-11-01
• Study Completion: 2027-11-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 102

Inclusion Criteria

• Histologically proven primary high-risk Retroperitoneal sarcoma(RPS) (Including Dedifferentiated liposarcoma (DDLPS), leiomyosarcoma(LMS), Undifferentiated pleomorphic sarcoma(UPS), Solitary fibrous tumor(SFT)).

• Primary localized RPS without histories of surgical resection, chemo- or radio-therapy, targeted therapy. Patients who underwent laparotomy with biopsy only will also be considered as primary cases.

• Without histories of second malignant tumors.

• In DDLPS

  • Diagnosis should be confirmed based on MDM2(Mouse double minute 2 homolog) and CDK4(Cyclin-dependent kinase 4) expression on IHC (immunohistochemistry), while MDM2 amplification in the Fish test is highly recommended.
  • All grade 2-3 DDLPS can be included.

• In LMS

  • All grades of LMS can be included.
  • Tumor size ≥10cm

• In UPS or SFT

  • All grades of UPS can be included.
  • High-risk SFT with a score ≥6 in 'Risk stratification of SFT for development of metastasis' introduced in The 5th edition of the WHO(World Health Organization) Soft tissue sarcoma classification.

• Sarcoma without protruding across the diaphragm

• Possibility of R0/R1 resection evaluated through preoperative MDT(multi-disciplinary team) discussion

• No multi-organ or system dysfunction/failure or patients with slight dysfunction of organ/system could be easily recovered

• Tolerable of chemotherapy and surgery through MDT evaluation and tests.

• American Society of Anesthesiologist (ASA) ≤3

• Fully understand the informs and consent to participate in the study.

Exclusion Criteria

• Sarcoma confirmed originating from the GI tract, uterus, or urinal tract.
• Patients included in the study through preoperative biopsy or MDT discussion, with WDLPS, grade 1 LPS, or other types of tumors not mentioned in the Inclusion criteria evaluating through final pathological findings.
• Sarcoma protruded into the chest cavity evaluated through preoperative imaging or surgical reports.
• Metastasis confirmed pathologically or highly suspicious metastatic lesions through radiological findings, PET-CT(Positron emission tomography) is highly recommended, MDT discussion and evaluation are needed.
• Histories of administration of Anthracyclines, Ifosfamide, and targeted agents.
• Severe contradiction to surgery and chemotherapies, including persistent myelosuppression, myocardial/cerebral/pulmonary infarction, uncontrolled cardiac arrhythmia, etc within the last 6 months
• Indication of severe infection or undergoing surgeries with high-risk hemorrhages in one month.
• Persistent one or more organ or system dysfunctions, could not be recovered prior to the study.
• Female patients who are pregnant or breastfeeding or female and male patients of reproductive potential who are not willing to employ effective birth control methods.
• Patients with psychological conditions

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
The Neoadjuvant Therapy Group	Doxorubicin+Ifosfamide+Anlotinib(AI+A)	Neoadjuvant chemotherapy + Target therapy+ Radical resectional Surgery Drugs: Doxorubicin（PLD） 40mg/㎡ d1, Ifosfamide 1g/㎡ d1-5, Anlotinib10mg d1-14 Q3weeks \* 3 Circles, Watch-Wait 4-6 weeks
The Neoadjuvant Therapy Group	Radical Surgery	Neoadjuvant chemotherapy + Target therapy+ Radical resectional Surgery Drugs: Doxorubicin（PLD） 40mg/㎡ d1, Ifosfamide 1g/㎡ d1-5, Anlotinib10mg d1-14 Q3weeks \* 3 Circles, Watch-Wait 4-6 weeks
The Surgery only Group	Radical Surgery	Procedure: Radical resectional surgery

Primary Outcome Measures

Name	Time	Method
3-year Progression Free Survival(PFS)	3 years after first patient enrolled in	Progression free survival will be measured from the date of surgery to the date of progression or death, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
1-year PFS	1year after first patient enrolled in.	Progression free survival will be measured from the date of surgery to the date of progression or death, whichever occurs first.
5-year OS	5 years after first patient enrolled in	OS will be measured from the date of surgery to the date of death, whatever the causes of death.
Safety and toxicity of neoadjuvant therapy	1-d, 7-d after the first date of each neoadjuvant therapy session.	Safety and toxicity will be evaluated through blood tests, echocardiography, ECG, etc.
Postoperative morbidities	30-d, 90-d, 1-year separately after the date of surgery.	Operative outcomes including morbidities will be collected and compared in two groups.
5-year PFS	5 years after first patient enrolled in.	Progression free survival will be measured from the date of surgery to the date of progression or death, whichever occurs first.
1 year Overall survival(OS)	1year after first patient enrolled in	OS will be measured from the date of surgery to the date of death, whatever the causes of death.
3-year OS	3 years after first patient enrolled in	OS will be measured from the date of surgery to the date of death, whatever the causes of death.

Trial Locations

Locations (6)

The Affiliated Hospital of Qingdao University; 🇨🇳 Qingdao, Shandong, China

First Affiliated Hospital Xi'an Jiaotong University; 🇨🇳 Xi'an, Shanxi, China

Shanghai Zhongshan Hospital; 🇨🇳 Shanghai, Shanghai, China

Beijing Friendship Hospital; 🇨🇳 Beijing, Beijing, China

Shanghai Cancer Hospital, Minhang Branch; 🇨🇳 Shanghai, Shanghai, China

Peking University First Hospital; 🇨🇳 Beijing, Beijing, China