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

NCT05844813 | Enrolling By Invitation Phase 4 DMC

• 2 other identifiers: PKUIH-RPS01Z221100007422042
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 6

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

Keywords

Retroperitoneal Sarcoma; Neoadjuvant therapy; Target therapy; Survival

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 1-year PFS

  1year after first patient enrolled in.

• 1 year Overall survival(OS)

  1year after first patient enrolled in

• 3-year OS

  3 years after first patient enrolled in

• 5-year PFS

  5 years after first patient enrolled in.

• 5-year OS

  5 years after first patient enrolled in

Study Arms (2)

The Neoadjuvant Therapy Group

EXPERIMENTAL

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

Drug: Doxorubicin+Ifosfamide+Anlotinib(AI+A); Procedure: Radical Surgery

The Surgery only Group

ACTIVE COMPARATOR

Procedure: Radical resectional surgery

Procedure: Radical Surgery

Interventions

Doxorubicin+Ifosfamide+Anlotinib(AI+A) DRUG

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

The Neoadjuvant Therapy Group

Radical Surgery PROCEDURE

Radical sarcoma resectional surgery

The Neoadjuvant Therapy Group; The Surgery only Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Peking University International Hospital: lead
• Shanghai Zhongshan Hospital: collaborator
• The Affiliated Hospital of Qingdao University: collaborator
• Peking University First Hospital: collaborator
• Shanghai Cancer Hospital, China: collaborator
• First Affiliated Hospital Xi'an Jiaotong University: collaborator
• Beijing Friendship Hospital: collaborator

Study Sites (6)

Beijing Friendship Hospital

Beijing, Beijing Municipality, China

Location

Peking University First Hospital

Beijing, Beijing Municipality, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Location

Shanghai Cancer Hospital, Minhang Branch

Shanghai, Shanghai Municipality, China

Location

Shanghai Zhongshan Hospital

Shanghai, Shanghai Municipality, China

Location

First Affiliated Hospital Xi'an Jiaotong University

Xi’an, Shanxi, China

Location

Study Officials

• Chenghua Luo, MD, PhD

  Peking University International Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: It is a prospective non-randomized controlled study. After meeting the inclusion and exclusion criteria, patients will be allocated either into the Surgery-only Group or the Neoadjuvant therapy group. Patients in the surgery-only group will directly undergo surgeries after the confirmation of diagnosis through pre-operative biopsy, while in the neoadjuvant therapy group, patients will receive neoadjuvant chemotherapy combined with target treatment for three circles followed by the sarcoma resectional surgeries.

Study Record Dates

• First Submitted: April 16, 2023
• First Posted: May 6, 2023
• Study Start: November 1, 2022
• Primary Completion: November 1, 2025
• Study Completion (Estimated): November 1, 2027
• Last Updated: May 12, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)