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

Germ Cell Tumor Clinical Trial

— SCRRYST  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06341998
• Other study ID #: HERO2020
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: June 1, 2020
• Est. completion date: February 1, 2024

Study information

• Verified date: March 2024
• Source: Shandong First Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: February 1, 2024
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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 > 50% or BNP < 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.

Related Conditions & MeSH terms

• Germ Cell Tumor
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Yolk Sac Tumor

Intervention

Drug:
• sirolimus combined with chemotherapy in the treatment of recurrent/refractory yolk sac tumor in children
The oral dose of sirolimus is 1mg/m2 daily (maximum 2 mg). Sirolimus whole blood trough concentration is measured 5 days after administration, with blood collected within half an hour before morning administration. Dose adjustment occurs weekly until the target range of 10-15ng/ml is achieved, followed by review every 21 days. Each cycle lasts for 21 days (every three weeks), and if treatment parameters are met as described in the study, cycle two and subsequent cycles begin on day 22. Treatment will be discontinued if there is drug-related dose-limiting toxicity or disease progression. Tumor response assessment will be repeated using AFP and LDH every one cycle and imaging examination every two cycles. Children who complete the trial may continue this regimen or undergo surgery or radiation therapy if their disease goes into remission.

Locations

Country	Name	City	State
China	Shandong Cancer Hospital and Institute	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Shandong First Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate Allocation 'Non-Randomized' implies that this is a multi-arm study, but only one arm has been specified. Objective Response Rate	ORR	12weeks
Secondary	Progression-free Survival	PFS	12weeks