Clinical trial NCT06341998: Clinical Study of Chemotherapy in the Treatment of Recurrent/Refractory Yolk Sac Tumor in Children
Official title: Clinical Study of Sirolimus Combined With Chemotherapy in the Treatment of Recurrent/Refractory Yolk Sac Tumor in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Germ Cell Tumor
Yolk Sac Tumor
Keywords: multiply relapsed or cisplatin refractory yolk sac tumor
sirolimus
germ cell tumor
mTOR
Lead sponsor: Shandong First Medical University
Sponsor class: OTHER
First posted: 2024-04-02
Enrollment: 32
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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\&#39;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.

Eligibility criteria: Inclusion Criteria:

1. The child must have histological evidence of an extracranial malignant germ cell tumor (vitelline sac tumor).
2. Children must be no more than 14 years old at the time of study participation.
3. The child must be resistant to at least two platinum-containing chemotherapy regiments or have relapse within 3 months of chemotherapy.
4. The child must have measurable lesions (recorded according to RECIST criteria) or non-evaluable disease with tumor marker AFP greater than 5 times the upper limit of normal.
5. Lansky performance status score ≥50.
6. The life expectancy of the child must exceed 6 weeks.
7. The child must have recovered from the response to all previous anticancer treatments.
8. No serious organ dysfunction: normal cardiac function (ejection fraction \&gt; 50% or BNP \&lt; 2000pg/ml); Liver function: alanine aminotransferase increased less than 5 times the upper limit of normal, bilirubin increased less than 3 times the upper limit of normal; Renal function: creatinine and urea nitrogen levels below the normal range; The white blood cells were greater than 3×109/L, and the platelets were greater than 100×109/L.
9. Obtain the informed consent of the guardian and sign the informed consent.

Exclusion Criteria:

1. Patients with other tumors.
2. Heart, brain, liver, kidney and other organ failure patients.

Primary outcomes:
measure: Objective Response Rate Allocation 'Non-Randomized' implies that this is a multi-arm study, but only one arm has been specified. Objective Response Rate
timeFrame: 12weeks
Secondary outcomes:
measure: Progression-free Survival
timeFrame: 12weeks
Other outcomes:
Locations:
city: Jinan
country: China
facility: Shandong Cancer Hospital and Institute
state: Shandong
Study officials:
affiliation: Shandong Cancer Hospital and Institute
name: Jingfu Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: