A Phase 2/3 interventional study of sirolimus combined with chemotherapy in the treatment of recurrent/refractory yolk sac tumor in children in Germ Cell Tumor and Yolk Sac Tumor, sponsored by Shandong First Medical University. Completed at 1 site in China. Open to participants aged 1 Year to 18 Years. Per ClinicalTrials.gov, last updated 2025-09-19.
Sponsored by Shandong First Medical University · Phase 2/3, Interventional, and Treatment
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).
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.
51 studies on the registry are indexed under Endodermal Sinus Tumor; 7 are open to participants now.
This study's enrollment of 32 is close to the median of 30 across 39 interventional studies indexed under Endodermal Sinus Tumor.
Browse Endodermal Sinus Tumor studies →Shandong First Medical University is the lead sponsor of 9 studies on the registry; 5 are open to participants now.
Compared within Endodermal Sinus Tumor, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Neoplasms, Germ Cell and Embryonal. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria：
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: 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.
ORR: Objective Response Rate Allocation 'Non-Randomized' implies that this is a multi-arm study, but only one arm has been specified. Objective Response Rate
Each treatment cycle spans 21 to 28 days (equivalent to every 3 to 4 weeks). Provided that the treatment criteria outlined in the study are satisfied, the second and subsequent cycles will commence on either the 22nd or 29th day. In the event of severe drug-related adverse reactions, treatment will be discontinued, and the patient will be classified as having PD. Tumor response assessment will entail the re-evaluation of AFP and LDH levels every cycle, alongside imaging examinations every two cycles. Should AFP levels demonstrate a continuous increase over two consecutive monitoring sessions following the initial treatment cycle, or if imaging results indicate tumor progression, a diagnosis of PD will be made, resulting in the termination of the clinical trial. For pediatric patients whose trials have been terminated, alternative anti-tumor therapies will be administered in accordance with their individual clinical conditions.
Time frame: Each treatment cycle spans 3 to 4 weeks, 1-4 cycles, last at lest 3 to 16 weeks.
Secondary endpoints included the progression-free survival (PFS) rate, overall survival (OS), and safety profile.
The study employed a Simon's two-stage optimal design with a one-sided alpha of 20% and 95% power to test the null hypothesis of ≤5% objective response rate (ORR) against the alternative hypothesis of ≥20% ORR. In the first stage, 10 patients were enrolled: if ≤1 patient achieved an objective response (CR/PR), the trial would be terminated for futility. Otherwise, enrollment would expand to a total of 32 patients. The regimen would be considered promising if ≥6 objective responses were observed in the final analysis. The median PFS and overall survival (OS) were estimated using the Kaplan-Meier method, implemented through the "survival" and "survminer" packages in R software (version 4.2.2). Correlations between OS and other endpoints were assessed at the patient level using Spearman's rank correlation coefficient (ρ).
Time frame: After each patient completed the clinical trial, they underwent imaging assessment examinations at 3/6/9/12/18/24/30/36/48/60 months after the end of the treatment.
Plan to share: No
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Ran from Jun 2020 to primary completion in Jan 2024, 43 months.
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Shandong First Medical University