Clinical trial NCT05844813: Neoadjuvant Chemotherapy Combined With Targeted Treatment in High-risk Retroperitoneal Sarcoma
Official title: Neoadjuvant Chemotherapy Combined With Targeted Treatment in High-risk Retroperitoneal Sarcoma-- A Nationwide Multicentered Prospective Controlled Study
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE4
Conditions: Retroperitoneal Sarcoma
Keywords: Retroperitoneal Sarcoma
Neoadjuvant therapy
Target therapy
Survival
Lead sponsor: Peking University International Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Zhongshan Hospital
name: The Affiliated Hospital of Qingdao University
name: Peking University First Hospital
name: Shanghai Cancer Hospital, China
name: First Affiliated Hospital Xi'an Jiaotong University
name: Beijing Friendship Hospital
First posted: 2023-05-06
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.


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.

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

Primary outcomes:
measure: 3-year Progression Free Survival(PFS)
timeFrame: 3 years after first patient enrolled in
Secondary outcomes:
measure: 1-year PFS
timeFrame: 1year after first patient enrolled in.
measure: 1 year Overall survival(OS)
timeFrame: 1year after first patient enrolled in
measure: 3-year OS
timeFrame: 3 years after first patient enrolled in
measure: 5-year PFS
timeFrame: 5 years after first patient enrolled in.
measure: 5-year OS
timeFrame: 5 years after first patient enrolled in
measure: Safety and toxicity of neoadjuvant therapy
timeFrame: 1-d, 7-d after the first date of each neoadjuvant therapy session.
measure: Postoperative morbidities
timeFrame: 30-d, 90-d, 1-year separately after the date of surgery.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Shanghai Cancer Hospital, Minhang Branch
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital
state: Shanghai
city: Xi'an
country: China
facility: First Affiliated Hospital Xi'an Jiaotong University
state: Shanxi
Study officials:
affiliation: Peking University International Hospital
name: Chenghua Luo, MD, PhD
role: STUDY_CHAIR
References: