Thalidomide Combined With Chemotherapy in the Treatment of Relapsed or Refractory Yolk Sac Tumor

Clinical Study of Thalidomide Combined With Chemotherapy in the Treatment of Relapsed or Refractory Yolk Sac Tumor in Children

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 thalidomide with nab-paclitaxel, gemcitabine, and epirubicin (T-TGA) for children with repeated relapsed or refractory yolk sac tumor (rrrYST).

Study Overview

• Status: Completed
• Conditions: Germ Cell Tumor; Yolk Sac Tumor
• Intervention / Treatment: Drug: Thalidomide combined with TGA chemotherapy (nab-paclitaxel + gemcitabine+ epirubicin)

Detailed Description

Thalidomide (THD) is currently widely used in the treatment of immune rheumatic diseases, blood tumors and solid tumors. Solid tumors are mostly used in the treatment of lung cancer, liver cancer, stomach cancer, colorectal cancer, pancreatic cancer, etc., and are limited to patients with advanced or advanced tumors. The main mechanisms of its action are inhibition of angiogenesis, immune regulation, induction of apoptosis, target teratogenesis and so on. However, whether from animal experiments or clinical studies, thalidomide alone or in combination with chemotherapy has not been seen to have a very effective therapeutic effect or exact clinical application in the treatment of these solid tumors.

According to the latest relevant case analysis reports and clinical trial results abroad, TIP regimen is still the priority recommended treatment regimen in the previous data for children with recurrent and refractory malignant germ cell tumors. However, the combination of Sirolimus and TIC regimen (nab-paclitaxel + isocyclophosphamide + carboplatin) previously explored by our research group can greatly improve the remission rate of recurrent and refractory germinal cell tumors, especially for recurrent and refractory yolk sac tumors, a certain proportion can be cured or the opportunity for surgery and radiotherapy can be obtained to achieve cure. However, there are still some children who are insensitive or progress again after 2 cycles of remission. For these children with multiple relapsed or particularly difficult yolk sac tumors, there is no effective treatment plan in the world at present, and there is no relevant clinical trial. However, through our clinical experience and understanding in the treatment process of these children, The results of thalidomide combined with TGA chemotherapy regimen (nab-paclitaxel + gemcitabine + epirubicin) were satisfactory. Therefore, we hope to evaluate the therapeutic effectiveness and adverse reactions of this regimen through clinical trials, so as to provide an effective treatment option for children with recurrent and refractory yolk sac tumor.

This paper is the first one to report the treatment combining thalidomide with nab-paclitaxel, gemcitabine, and epirubicin (T-TGA) for children with repeated relapsed or refractory yolk sac tumor (rrrYST).

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital and Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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 18 years old at the time of study participation.
3. The patients were children with vitelline cystic tumor who were resistant to drugs after at least two platinum-containing chemotherapy regimes or whose disease recurred within 3 months after chemotherapy regimes, or who recurred again or repeatedly after treatment with Sirolimus combined with TIC chemotherapy regimes.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: thalidomide combined with chemotherapy in the treatment of relapsed or refractory yolk sac tumor; This study employed an open single-group clinical laboratory design method (Simon Phase II study) to investigate the efficacy and safety of combining thalidomide with TGA chemotherapy (nab-paclitaxel + gemcitabine+ epirubicin) in the treatment of children with recurrent or refractory YST. 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 or refractory yolk sac tumor, evaluating overall remission rate (ORR) and event-free survival rate (EFS), as well as monitoring and recording chemotherapy-related side effects.

Drug: Thalidomide combined with TGA chemotherapy (nab-paclitaxel + gemcitabine+ epirubicin); The oral dose of thalidomide is 1.5-2.5mg/kg/d daily (maximum 28g). 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Proportion of participants achieving partial or complete response，Measurement: Imaging (CT/MRI) every 2 cycles per RECIST 1.1；Serum AFP reduction ≥90% from baseline.	Every 3 weeks per cycle, up to 6 cycles

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Tumor Response Evaluation	Assessment of tumor size and characteristics to evaluate treatment response. Method: Contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) scans Outcome Metrics: Complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) based on RECIST 1.1 criteria	Every 6 weeks (i.e., every 2 chemotherapy cycles)

Collaborators and Investigators

• Sponsor: Shandong First Medical University
• Investigators: Study Director: Jingfu Wang, MD, Shandong Cancer Hospital and Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2021
• Primary Completion (Actual): June 16, 2024
• Study Completion (Actual): June 16, 2024

Study Registration Dates

• First Submitted: June 17, 2024
• First Submitted That Met QC Criteria: June 21, 2024
• First Posted (Actual): June 24, 2024

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 14, 2025
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: thalidomide; relapsed or refractory yolk sac tumor
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Mesonephroma; Pathological Conditions, Signs and Symptoms; Recurrence; Neoplasms, Germ Cell and Embryonal; Endodermal Sinus Tumor; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Antibiotics, Antineoplastic; 130-nm albumin-bound paclitaxel
• Other Study ID Numbers: HERO2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No