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

NCT ID: NCT05844813

Last Updated: 2023-05-12

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE4
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-01
• Study Completion Date: 2027-11-01

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.

Conditions

Retroperitoneal Sarcoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

The Neoadjuvant Therapy Group

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

Group Type: EXPERIMENTAL

Doxorubicin+Ifosfamide+Anlotinib(AI+A)

Intervention Type: DRUG

Doxorubicin（PLD） 40mg/㎡ d1, Ifosfamide（I） 1g/㎡ d1-5, Anlotinib（A）10mg d1-14 Q3weeks \* 3 Circles

Radical Surgery

Intervention Type: PROCEDURE

Radical sarcoma resectional surgery

The Surgery only Group

Procedure: Radical resectional surgery

Group Type: ACTIVE_COMPARATOR

Radical Surgery

Intervention Type: PROCEDURE

Radical sarcoma resectional surgery

Interventions

Doxorubicin+Ifosfamide+Anlotinib(AI+A)

Doxorubicin（PLD） 40mg/㎡ d1, Ifosfamide（I） 1g/㎡ d1-5, Anlotinib（A）10mg d1-14 Q3weeks \* 3 Circles

Intervention Type: DRUG

Radical Surgery

Radical sarcoma resectional surgery

Intervention Type: PROCEDURE

Eligibility Criteria

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.

• 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

Exclusion Criteria

• Sarcoma confirmed originating from the GI tract, uterus, or urinal tract.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: collaborator

The Affiliated Hospital of Qingdao University

OTHER

Sponsor Role: collaborator

Peking University First Hospital

OTHER

Sponsor Role: collaborator

Shanghai Cancer Hospital, China

OTHER

Sponsor Role: collaborator

First Affiliated Hospital Xi'an Jiaotong University

OTHER

Sponsor Role: collaborator

Beijing Friendship Hospital

OTHER

Sponsor Role: collaborator

Peking University International Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jun Chen

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Chenghua Luo, MD, PhD

Role: STUDY_CHAIR

Peking University International Hospital

Locations

Beijing Friendship Hospital

Beijing, Beijing Municipality, China

Peking University First Hospital

Beijing, Beijing Municipality, China

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Shanghai Cancer Hospital, Minhang Branch

Shanghai, Shanghai Municipality, China

Shanghai Zhongshan Hospital

Shanghai, Shanghai Municipality, China

First Affiliated Hospital Xi'an Jiaotong University

Xi’an, Shanxi, China

Countries

China

Other Identifiers

Z221100007422042

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

PKUIH-RPS01

Identifier Type: -

Identifier Source: org_study_id