Clinical Study of Chemotherapy in the Treatment of Recurrent/Refractory Yolk Sac Tumor in Children

NCT ID: NCT06341998

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2024-02-01

Brief Summary

Remarkable progress has been made in treating germ-cell tumor (GCT) through the use of platinum-based regimens. However, part of yolk sac tumor (YST) with cisplatin resistance or recurrence is nevertheless prone to relapse after second-line treatment. This leaves a gap in effective treatment, which needs to be filled by novel therapeutic approaches. This paper is the first one to report the treatment combining sirolimus with nab-paclitaxel, ifosfamide, and carboplatin (S-TIC) for children with repeated relapsed or refractory yolk sac tumor (rrrYST).

Detailed Description

According to the latest relevant foreign case analysis reports and clinical trial results, the TIP regimen remains the recommended treatment for patients with recurrent and refractory malignant germ-cell tumors based on previous data. Carboplatin has been proven effective and less toxic in children with MGCTs, while cisplatin is more commonly used in early stages. In our research group's previously explored TIC scheme (albumin paclitaxel + ifosfamide + carboplatin), cisplatin is often substituted with carboplatin. Additionally, albumin paclitaxel replaces traditional paclitaxel due to its lower adverse reaction rate and higher tumor tissue uptake accumulation, forming the TIC regimen. Our preliminary clinical work has shown that the TIC regimen effectively improves remission rates of recurrent refractory germ cell tumors, particularly yolk sac tumors. For a small number of children who are not responsive to the TIC regimen, combining Sirolimus (an mTOR inhibitor) significantly enhances remission rates of recurrent refractory yolk sac tumors. This approach can potentially lead to cure or achieve surgery and radiotherapy within a curative timeframe. Therefore, this study aims to determine the efficacy of combining mTOR inhibitor Sirolimus with the TIC chemotherapy regimen (albumin-paclitaxel + isocyclophosphamide + carboplatin) in treating recurrent or refractory vitelline cyst tumors, providing a novel and effective therapeutic option for children with recurrent and refractory MGCTs.

Conditions

Germ Cell Tumor; Yolk Sac Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

sirolimus combined with chemotherapy treat recurrent/refractory yolk sac tumor in children

This study employed an open single-group clinical laboratory design method (Simon Phase II study) to investigate the efficacy and safety of combining sirolimus with TIC chemotherapy (albumin-paclitaxel + isocyclophosphamide + carboplatin) in the treatment of children with recurrent/refractory vitellocystoma. AFP levels were assessed after each course of treatment, while imaging evaluations were conducted every two courses. The remission rate following chemotherapy in this single-group clinical trial was compared to that reported in the literature for treating recurrent/refractory yolk sac tumor, evaluating overall remission rate (ORR) and progresion-free survival rate (PFS) and overall survival (OS), as well as monitoring and recording chemotherapy-related side effects.

Group Type: EXPERIMENTAL

sirolimus combined with chemotherapy in the treatment of recurrent/refractory yolk sac tumor in children

Intervention Type: DRUG

The planned treatment protocol comprised four cycles of the S-TIC regimen, which included sirolimus administered orally at a dose of 1 mg/m² from day 1 to day 21-28, nab-paclitaxel at a dose of 200 mg/m² on day 1, ifosfamide at a dose of 1200 mg/m² from day 2 to day 5, and carboplatin at a dose of 400 mg/m² on day 2. Additionally, mesna and sulfamethoxazole were prescribed to prevent hemorrhagic cystitis and Pneumocystis Jirovecii Pneumonia (PJP), respectively. Each cycle spanned a duration of three to four weeks. AFP levels were evaluated at the end of each cycle, and radiological assessments were conducted every two cycles. Surgical intervention decisions were made based on the results of these assessments.

Interventions

sirolimus combined with chemotherapy in the treatment of recurrent/refractory yolk sac tumor in children

The planned treatment protocol comprised four cycles of the S-TIC regimen, which included sirolimus administered orally at a dose of 1 mg/m² from day 1 to day 21-28, nab-paclitaxel at a dose of 200 mg/m² on day 1, ifosfamide at a dose of 1200 mg/m² from day 2 to day 5, and carboplatin at a dose of 400 mg/m² on day 2. Additionally, mesna and sulfamethoxazole were prescribed to prevent hemorrhagic cystitis and Pneumocystis Jirovecii Pneumonia (PJP), respectively. Each cycle spanned a duration of three to four weeks. AFP levels were evaluated at the end of each cycle, and radiological assessments were conducted every two cycles. Surgical intervention decisions were made based on the results of these assessments.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• The pediatric patient is required to present histological confirmation of an extracranial yolk sac tumor.
• At the time of enrollment, the patient must be 18 years of age or younger, with no restrictions based on gender
• The patient must exhibit disease progression following a minimum of two platinum-based chemotherapy regimens or experience a relapse after the completion of treatment
• The patient must have measurable lesions, documented in accordance with the RECIST criteria, or possess an unassessable disease with alpha-fetoprotein (AFP) levels exceeding five times the upper limit of normal
• The Lansky performance status score must be 50 or higher, and the patient's life expectancy should be greater than 12 weeks
• The patient must have fully recovered from any prior adverse effects related to anti-cancer treatments

Exclusion Criteria

• a history of previous tumors
• organ failure, specifically involving the heart, brain, liver, or kidneys.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shandong First Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jingfu Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Shandong Cancer Hospital and Institute

Locations

Shandong Cancer Hospital and Institute

Jinan, Shandong, China

Countries

China

Other Identifiers

HERO2020

Identifier Type: -

Identifier Source: org_study_id