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

Retroperitoneal Sarcoma Clinical Trial

— NATARS  

Official title:

Neoadjuvant Chemotherapy Combined With Targeted Treatment in High-risk Retroperitoneal Sarcoma-- A Nationwide Multicentered Prospective Controlled Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05844813
• Other study ID #: PKUIH-RPS01
• Secondary ID: Z221100007422042
• Status: Enrolling by invitation
• Phase: Phase 4
• Start date: November 1, 2022
• Est. completion date: November 1, 2027

Study information

• Verified date: May 2023
• Source: Peking University International Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 102
• Est. completion date: November 1, 2027
• Est. primary completion date: November 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Retroperitoneal Sarcoma
• Sarcoma

Intervention

Drug:
• Doxorubicin+Ifosfamide+Anlotinib(AI+A)
Doxorubicin(PLD) 40mg/? d1, Ifosfamide(I) 1g/? d1-5, Anlotinib(A)10mg d1-14 Q3weeks * 3 Circles

Procedure:
• Radical Surgery
Radical sarcoma resectional surgery

Locations

Country	Name	City	State
China	Beijing Friendship Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Shanghai Cancer Hospital, Minhang Branch	Shanghai	Shanghai
China	Shanghai Zhongshan Hospital	Shanghai	Shanghai
China	First Affiliated Hospital Xi'an Jiaotong University	Xi'an	Shanxi

Sponsors (7)

Lead Sponsor	Collaborator
Peking University International Hospital	Beijing Friendship Hospital, First Affiliated Hospital Xi'an Jiaotong University, Peking University First Hospital, Shanghai Cancer Hospital, China, Shanghai Zhongshan Hospital, The Affiliated Hospital of Qingdao University

Country where clinical trial is conducted

China, 

Outcome

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