Phase II Study of Irinotecan Liposome (II) Combined With Temozolomide and Fluzoparib in Recurrent or Metastatic Ewing Sarcoma

NCT06827717 | Recruiting Phase 2

• 1 other identifier: B2024-859-01
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The current study is an investigator-initiated, single-arm phase 2 study that enrolled patients with recurrent and/or metastatic Ewing sarcoma for the treatment of Irinotecan Liposome (II) Combined with Temozolomide and Fluzoparib as the second-line treatment.

Conditions

Ewing Sarcoma

Keywords

Ewing sarcoma; irinotecan liposome; temozolomide; fluzoparib; PARP

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate(ORR)

  Objective Response Rate(CR+PR), defined as best overall response (complete or partial response) across all assessment time points, determined using RECIST v1.1 criteria.

  From Cycle 1 Day 1 (C1D1) to treatment discontinuation for any reason, average of 4 months

Secondary Outcomes (5)

• Disease Control Rate （DCR）

  From Cycle 1 Day 1 (C1D1) to treatment discontinuation for any reason, average of 4 months

• Duration of Response （DoR）

  From first confirmed CR or PR to confirmed PD, average of 4 months

• Progression Free Survival (PFS)

  From Cycle 1 Day 1 (C1D1) to first documented objective PD or death if PD does not occur, average of 4 months

• Overall Survival (OS)

  From Cycle 1 Day 1 (C1D1) to death from any cause, average of 12 months

• Incidence of Adverse Events [safety and tolerability]

  From Cycle 1 Day 1 (C1D1) to 30 days after the last dose of study treatment

Study Arms (1)

irinotecan liposome (II) + temozolomide + fluzoparib

EXPERIMENTAL

irinotecan liposome (II) combined with temozolomide and fluzoparib

Drug: irinotecan liposome (II) + temozolomide + fluzoparib

Interventions

irinotecan liposome (II) + temozolomide + fluzoparib DRUG

Drug Irinotecan Hydrochloride Liposome Injection（II）56.5mg/m2, IV infusion administered on day 1 of every 28-day cycle until disease progression, unacceptable toxicity or death. Other names: HR070803. Drug Fluzoparib 50mg PO bid, administered continuously until disease progression, unacceptable toxicity or death. 28 days as a treatment cycle. Other names: SHR-3162. Drug Temozolomide 30mg/m2 PO qd, administered on day 1 to day 5 of every 28-day cycle until disease progression, unacceptable toxicity or death.

irinotecan liposome (II) + temozolomide + fluzoparib

Eligibility Criteria

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

You may qualify if:

• Patients aged 18 to 75 years (calculated as of the date of signing the informed consent), regardless of gender.
• \. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 3. Histologically confirmed advanced or metastatic Ewing sarcoma, with at least one measurable lesion that has not been treated locally (according to RECIST v1.1, this measurable lesion must have a maximum diameter of ≥ 10 mm on spiral CT scans or a short diameter of ≥ 15 mm for enlarged lymph nodes).
• \. The primary tumor or locally recurrent tumor cannot be completely resected through surgery or other local treatments (e.g., stereotactic radiosurgery, argon-helium knife, ultrasound-guided focused ultrasound, etc.); first-line chemotherapy (VAC/IE) has failed, leading to distant metastasis, and the metastatic tumors cannot be completely resected through surgery or other local treatments; or the patient refuses surgery or other local treatments.
• \. Expected survival of ≥ 12 weeks. 6. Basic normal function of major organs, with severe abnormalities in blood, heart, lung, liver, kidney, bone marrow functions, or immune deficiency diseases meeting protocol requirements:
• Complete Blood Count (CBC): (No blood transfusion, use of Granulocyte-Colony Stimulating Factor \[G-CSF\], or corrective therapy within 14 days prior to screening)
• \- Hemoglobin ≥ 90 g/L;
• Neutrophil count ≥ 1.5 × 10\^9/L;
• Platelet count ≥ 75 × 10\^9/L;
• Biochemical Tests: (No albumin infusion within 14 days)
• Albumin ≥ 29 g/L;
• Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN);
• Total bilirubin (TBIL) ≤ 1.5 times ULN;
• Creatinine (Cr) ≤ 1.5 times ULN or Cr clearance \> 50 mL/min (Cockcroft-Gault formula):
• Male: Cr clearance = ((140 - age) × weight) / (72 × blood Cr)
• Female: Cr clearance = ((140 - age) × weight) / (72 × blood Cr) × 0.85

You may not qualify if:

• \. Plans to receive any other anti-tumor treatments during this trial. 2. Received radiotherapy for Ewing sarcoma within 4 weeks prior to the first administration of the study drug, or received other investigational drugs or cell therapies.
• \. Presence of intracranial tumor lesions diagnosed by imaging. 4. History of other active malignancies within the past 5 years, or currently having other active malignancies aside from Ewing sarcoma. Curatively treated localized tumors, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, prostate in situ carcinoma, cervical in situ carcinoma, and breast in situ carcinoma, are allowed.
• \. Presence of clinically symptomatic ascites requiring paracentesis or drainage, or having undergone paracentesis within the last 3 months; only those with small amounts of ascites detected by imaging but without clinical symptoms are excluded; uncontrolled or moderate to severe pleural effusion or pericardial effusion; evidence of intraperitoneal free air that cannot be explained by paracentesis or recent surgical procedures.
• \. History of epilepsy, or having experienced diseases that can induce seizures (including transient ischemic attacks, strokes-not just isolated imaging findings of cerebral ischemia without clinical history, or head trauma with loss of consciousness requiring hospitalization) within 12 months prior to the first administration of the study drug.
• \. Previous treatment with PARP inhibitors, irinotecan, temozolomide, including but not limited to fluzoparib.
• \. History of allergic reactions, including severe drug allergies or drug hypersensitivity; known allergies or intolerances to fluzoparib, liposomal irinotecan, temozolomide, or their excipients.
• \. Severe infections (CTCAE grade \> 2) occurring within 4 weeks prior to the first administration of the study drug, such as severe pneumonia requiring hospitalization, bacteremia, or infections with complications; baseline chest imaging indicating active pulmonary inflammation, presence of infection symptoms and signs within 2 weeks before the first administration of the study drug, or requiring oral or intravenous antibiotic treatment (excluding prophylactic use of antibiotics).
• \. Cannot discontinue the use of medications that may affect P-glycoprotein (P-gp) during the study period.
• \. Use of strong or moderate inhibitors or inducers of hepatic drug-metabolizing enzyme CYP3A4 within 14 days prior to the first administration of the study drug.
• \. Presence of factors that impair swallowing, chronic diarrhea, bowel obstruction, or other factors affecting drug intake and absorption.
• \. History of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML), or having had other malignancies within 5 years prior to the first administration of this study (with the exception of completely resolved in situ cancers and malignancies determined by the investigator to have slow progression).
• \. Co-infection with other viral infections (anti-HCV positive, anti-HIV positive, HBsAg positive) or syphilis infection.
• \. History of immune deficiency (including positive human immunodeficiency virus \[HIV\] test, other acquired or congenital immune deficiencies) or history of organ transplantation.
• \. Known history of abuse of psychotropic substances, alcoholism, or drug abuse.
• \. Any condition judged by the investigator to pose a significant risk to patient safety or to affect the patient's ability to complete the study (such as poorly controlled hypertension, severe diabetes, thyroid disease, and psychiatric disorders) or any other situation.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Jiangsu Hengrui Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Sarcoma, Ewing

Interventions

irinotecan sucrosofate; Temozolomide; fluzoparib

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jin Wang, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jin Wang, MD

CONTACT

86+020-87343190; wangjinr@sysucc.org.cn

Chuanghzong Deng, MD

CONTACT

86+020-87340519; dengchzh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 10, 2025
• First Posted: February 14, 2025
• Study Start: April 15, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

CN (1)