Germ Cell TumorPhase 2/3SCRRYSTNCT06341998
Clinical Study of Chemotherapy in the Treatment of Recurrent/Refractory Yolk Sac Tumor in Children
A Phase 2/3 study testing sirolimus combined with chemotherapy in the treatment of recurrent/refractory yolk sac tumor in children in people with Germ Cell Tumor and Yolk Sac Tumor, run by Shandong First Medical University at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Germ Cell Tumor, Yolk Sac Tumor
- What is being tested?
- sirolimus combined with chemotherapy in the treatment of recurrent/refractory yolk sac tumor in children
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2020to 1 Feb 2024
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- a history of previous tumors
- organ failure, specifically involving the heart, brain, liver, or kidneys.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Study of Sirolimus Combined With Chemotherapy in the Treatment of Recurrent/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 sirolimus with nab-paclitaxel, ifosfamide, and carboplatin (S-TIC) for children with repeated relapsed or refractory yolk sac tumor (rrrYST).
Read the 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
- Being tested
- sirolimus combined with chemotherapy in the treatment of recurrent/refractory yolk sac tumor in children
- Keywords
- multiply relapsed or cisplatin refractory yolk sac tumor, sirolimus, germ cell tumor, mTOR
- Medical subject headings
- Neoplasms, Germ Cell and Embryonal, Endodermal Sinus Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimus combined with chemotherapy in the treatment of recurrent/refractory yolk sac tumor in childrenDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| sirolimus combined with chemotherapy treat recurrent/refractory yolk sac tumor in children | Experimental | 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. Receives: Drug: sirolimus combined with chemotherapy in the treatment of recurrent/refractory yolk sac tumor in children |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Each treatment cycle spans 3 to 4 weeks, 1-4 cycles, last at lest 3 to 16 weeks.
Secondary outcomes (1)
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).
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2024
- Study start1 Jun 2020
- Primary completion1 Jan 2024
- Study completion1 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Germ Cell TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shandong First Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jingfu Wang, MD, Principal investigator, Shandong Cancer Hospital and Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06341998
- Sponsor's protocol ID
- HERO2020
- Acronym
- SCRRYST
- Status last verified
- Sep 2025
- First submitted
- 26 Mar 2024
- Last updated
- 19 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of Sirolimus Combined With Chemotherapy in the Treatment of Recurrent/Refractory Yolk Sac Tumor in Children
- ClinicalTrials.gov ID
- NCT06341998
- Acronym / sponsor ID
- SCRRYST / HERO2020
- Conditions
- Germ Cell Tumor, Yolk Sac Tumor
- Keywords
- multiply relapsed or cisplatin refractory yolk sac tumor, sirolimus, germ cell tumor, mTOR
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Shandong First Medical UniversityUniversity, hospital or other
- Study start
- 1 Jun 2020 (actual)
- Primary completion
- 1 Jan 2024 (actual)
- Study completion
- 1 Feb 2024 (actual)
- First posted
- 2 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| sirolimus combined with chemotherapy treat recurrent/refractory yolk sac tumor in children | Experimental | Drug: sirolimus combined with chemotherapy in the treatment of recurrent/refractory yolk sac tumor in childrenThis 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. |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (2 listed)
- a history of previous tumors
- organ failure, specifically involving the heart, brain, liver, or kidneys.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sirolimus combined with chemotherapy in the treatment of recurrent/refractory yolk sac tumor in childrenThe 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. | Drug | sirolimus combined with chemotherapy treat recurrent/refractory yolk sac tumor in children |
Primary outcome
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
Time frame: Each treatment cycle spans 3 to 4 weeks, 1-4 cycles, last at lest 3 to 16 weeks.
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.
1 secondary outcome
Secondary endpoints included the progression-free survival (PFS) rate, overall survival (OS), and safety profile.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jingfu Wang, MD principal investigator
Shandong Cancer Hospital and Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing sirolimus combined with chemotherapy in the treatment of recurrent/refractory yolk sac tumor in children in people with Germ Cell Tumor and Yolk Sac Tumor, run by Shandong First Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Each treatment cycle spans 3 to 4 weeks, 1-4 cycles, last at lest 3 to 16 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2025.