Atypical Teratoid/Rhabdoid Tumors (AT/RTs)Phase 2NCT06853080
Feasibility of Using Bortezomib With or Without Chemotherapy in Patients With Atypical Teratoid/Rhabdoid Tumors
A Phase 2 study testing Bortezomib in people with Atypical Teratoid/Rhabdoid Tumors (AT/RTs) and Central Nervous System (CNS) Tumors, run by Taipei Medical University at 1 site in Taiwan.
Trial summary
Atypical teratoid/rhabdoid tumors (AT/RTs) account for 1%-2% of all central nervous system (CNS) tumors in children aged 0-14 years, yet are among the most common malignant CNS tumors in infants less than 1 year old. Read more about this study
- Who is it for?
- Ages 1 year to 20 years
- Conditions the study is for
- Atypical Teratoid/Rhabdoid Tumors (AT/RTs), Central Nervous System (CNS) Tumors
- What is being tested?
- Bortezomib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteTaiwan
- Study dates
- 2 Dec 2020to Dec 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with a valid Informed Consent Form signed by the Legal Guardian and/or Patient himself/herself.
- Patients with CNS AT/RT who were initially diagnosed at the age of 0-20 years.
- Disease Status:
- Cohort 1: Patients with newly diagnosed AT/RT; Cohort 2: Patients with recurrent or refractory CNS AT/RT who have had at least 1 line of chemotherapy with radiographically measurable disease as defined by at least 1 lesion that can be measured in 2 dimensions.
- Previous Anticancer Therapy:
- Cohort 1: No previous anticancer chemotherapy other than the use of corticosteroids.
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- Cohort 2: Patient has fully recovered from the acute toxic effects of chemotherapy, immunotherapy, or radiation therapy prior to entering this study:
- Myelosuppressive chemotherapy: Patient has not received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (4 and 6 weeks if prior temozolomide and nitrosourea, respectively).
- Hematopoietic growth factors: At least 7 days must have elapsed since the completion of therapy with a growth factor. At least 14 days must have elapsed after receiving pegfilgrastim.
- Biologic (anti-neoplastic agent): At least 7 days must have elapsed since completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur.
- Monoclonal antibodies: At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody.
- Radiation therapy: at least 3 months must have elapsed since any irradiation unless measurable disease progression occurs at a site separate from the irradiated area and the patient has recovered from toxicities associated with radiation therapy.
- Patients must have adequate organ and marrow function as defined below at enrollment and on day 1 of (or within 1 week prior to) each cycle:
- Absolute Neutrophil Count (ANC) ≥ 1,000/μL
- Platelets ≥ 100,000/μL at enrollment and on day 1 of each cycle
- Hemoglobin ≥ 8 g/dL (RBC transfusions allowed)
- Total bilirubin ≤ 1.5 times institutional upper limit of normal
- AST (SGOT) and ALT (SGPT) ≤ 2.5 times institutional upper limit of normal (4x ULN if liver involvement)
- Creatinine ≤ upper limits by age 0-5 years old: 0.8 mg/dL; 6-9 years old: 1.0 mg/dL; 10-12 years old: 1.2 mg/dL; 13-15 years old: male, 1.5 mg/dL; female, 1.4 mg/dL; 16 years or older: male, 1.7 mg/dL; female, 1.4 mg/dL
- LV Ejection Fraction of ≥ 50% by Echocardiogram
- Patient must have the Performance status defined by Lansky (< 16 years of age) or Karnofsky (≥16 years of age) Performace Status of ≥ 30 (Cohort 1) or ≥ 60 (Cohort 2).
- Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered to be ambulatory for the purpose of assessing the performance score.
- Female patients who are at least 10-years-old or are post-menarchal must have a negative serum or urine pregnancy test prior to enrollment
- Fertile patients must use effective contraception
- Life expectancy > 8 weeks
- No evidence of dyspnea at rest
- Fertile patients must use effective contraception
Who cannot join
- Clinically significant medical disorders that could compromise the ability to tolerate protocol therapy or that would interfere with the study procedures or results history.
- Presence of an active, uncontrolled infection.
- Existing peripheral neuropathy of NCI CTCAE v5.0 grade 2 or higher.
- Patients who have not recovered to baseline from previous treatment.
- Patients with hypersensitivity (not including local reactions) to BTZ, boron, or mannitol.
- Patients who have been previously treated with BTZ.
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- Requirement for constant administration of strong CYP3A4 interfering agents.
- Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or with rifampin, rifabutin, rifapentine, or St. John's wort within 7 days prior to initiation of BTZ.
- Inability to comply with the safety monitoring requirements of the study, as judged by the investigator.
- Female participants of childbearing potential cannot be pregnant or breast-feeding.
- Patients who are receiving other investigational drugs 14 or fewer days before enrollment.
- Patients with extra-CNS, extrarenal rhabdoid tumors or malignant renal rhabdoid tumors without CNS AT/RT are not eligible.
- Myocardial infarction within 6 months prior to enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. If for some reason an electrocardiogram is obtained before study enrollment, any abnormalities detected should be documented as clinically irrelevant.
- Other severe acute or chronic medical or psychiatric condition or any laboratory abnormality that may increase the risk associated with study participation or investigational product administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
- Subjects with known active infections requiring ongoing treatment (bacterial, fungal, or viral, including human immunodeficiency virus [HIV]).
Trial locations and contacts
1 site in 1 country.
About this study
Atypical teratoid/rhabdoid tumors (AT/RTs) account for 1%-2% of all central nervous system (CNS) tumors in children aged 0-14 years, yet are among the most common malignant CNS tumors in infants less than 1 year old. AT/RTs are defined by the loss of INI1 or, rarely, BRG1, encoded by the SMARCB1 and SMARCA4 genes, respectively. Patients with AT/RTs have dismal outcomes due to their highly malignant nature and young age at diagnosis. There remains no standard therapy for AT/RTs. Multimodal treatment strategies include a selective combination of conventional chemotherapy, high dose chemotherapy and stem cell rescue, intrathecal chemotherapy, and radiotherapy after tumor resection. The survival rate, even with aggressive treatment, is still low (2-year survival rate is 32.6%-44.6%). Moreover, currently used cytotoxic therapies incur some neurocognitive side effects, particularly in infants, highlighting the urgent need for novel targeted therapies.
Bortezomib (Velcade®) is the first generation proteasome inhibitor developed by Millennium Pharmaceuticals, Inc. as an anti-cancer medication. Bortezomib was approved by FDA for the treatment of adult patients with multiple myeloma and mantle cell lymphoma (newly diagnosed or relapse/recurrent disease). In children, the safety of BTZ has been proved in phase I clinical trial of patients with acute lymphoblastic leukemia, refractory or recurrent solid tumors, relapsed/refractory high-risk neuroblastoma. Recently, we found the proteasome-encoding genes were highly expressed in AT/RTs compared with that in normal brain tissues, correlated with the malignant phenotype of tumor cells, and were essential for tumor cell survival. Bortezomib targets proteostasis, inhibiting tumor growth and inducing apoptosis through p53 accumulation in three Myc-AT/RT cell lines and in mice with orthotopic xenografts of AT/RT. Our findings suggest that BTZ is a promising targeted therapy for Myc-AT/RTs (manuscript under review). To determine whether the other subgroups of ATRTs (i.e., SHH and TYR subgroups) are sensitive to BTZ, we conducted the in vivo drug test in 2 SHH-AT/RT cell lines (CHLA-02 and CHLA-04). Although CHLA-02 and CHLA-04 cell line were less sensitive to BTZ (IC50 of 15.1 (14.3-15.9) nM and 15.8 (14.5-17.3) nM, respectively) than Myc-AT/RT cell line (IC50 of 5.84 to 8.7 nM), these inhibitory concentrations are still clinically achievable (Cmax, 231.6-312.3 nM). Furthermore, the dependence on ubiquitin proteasome system for survival and high sensitivity to proteasome inhibitors have been reported in SMARCB1-deficient cancer cells. Additionally, we also observed the subgroup shifting in one infant with AT/RTs, from SHH subgroup of primary tumor to Tyr subgroup of the first recurrent tumor and Myc subgroup of the second recurrent tumor. Therefore, we hypothesize that BTZ treatment is potentially effective to all subgroups of CNS AT/RT and propose a clinical trial utilizing BTZ as an add-on therapy to standard and high-dose chemotherapy
- Being tested
- Bortezomib
- Medical subject headings
- Rhabdoid Tumor, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
4 cycles of Bortezomib treatment, with each cycle include 8 doses of Bortezomib at 1.3 mg/m2
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib single arm | Experimental | Bortezomib will be administered with chemotherapy on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 56-day treatment cycle for 4 cycles in newly diagnosed patients enrolled on Cohort 1.
Bortezomib will be administered as a single agent on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day treatment cycle for 4 cycles in all recurrent patients enrolled on Cohort 2. Receives: Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
Overall Response Rate (ORR) to bortezomib in patients with recurrent or refractory CNS AT/RT.
Measured: through study completion, an average of 1 year
Secondary outcomes (2)
Progression-Free Survival (PFS)
Progression-Free Survival (PFS) in patients with newly diagnosed CNS AT/RT
Measured: through study completion, an average of 1 year
Overall Survival (OS)
Overall Survival (OS) in patients with newly diagnosed CNS AT/RT
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2025
- Study start2 Dec 2020
- Primary completion31 Dec 2023
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Atypical Teratoid/Rhabdoid Tumors (AT/RTs)Studies of the same condition, open and under way.
- More trials run by Taipei Medical UniversityThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taipei Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06853080
- Sponsor's protocol ID
- N202010033
- Status last verified
- Jan 2025
- First submitted
- 17 Feb 2025
- Last updated
- 28 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Trial still conducted.
Publications
Ho WL, Hsieh MY, Liao YM, Chiou SS, Shiah HS, Chiang CH, Jou ST, Yen HJ, Lee YY, Liang ML, Yeh TC, Chou YC, Huang FL, Chen SH, Lee HL, Kuo CC, Yang YS, Chen SM, Tsai ML, Chang H, Hsieh KL, Fang CL, Chang CY, Wang JL, Chen CC, Loh JK, Lin PC, Lin TC, Wang SC, Tu YF, Cheng CN, Chuang JM, Tran HM, Sung SY, Lai I, Wu KS, Miser JS, Liu YL, Wong TT. A Phase Ib Case Series Using Bortezomib With Chemotherapy in Atypical Teratoid/Rhabdoid Tumors. Cancer Med. 2026 Sep;15(9):e72173. doi: 10.1002/cam4.72173.
PubMed 42745490
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility of Using Bortezomib With or Without Chemotherapy in Patients With Atypical Teratoid/Rhabdoid Tumors
- ClinicalTrials.gov ID
- NCT06853080
- Acronym / sponsor ID
- N202010033
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Taipei Medical UniversityUniversity, hospital or other
- Study start
- 2 Dec 2020 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- Dec 2025 (estimated)
- First posted
- 28 Feb 2025 (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.
Atypical teratoid/rhabdoid tumors (AT/RTs) account for 1%-2% of all central nervous system (CNS) tumors in children aged 0-14 years, yet are among the most common malignant CNS tumors in infants less than 1 year old. AT/RTs are defined by the loss of INI1 or, rarely, BRG1, encoded by the SMARCB1 and SMARCA4 genes, respectively. Patients with AT/RTs have dismal outcomes due to their highly malignant nature and young age at diagnosis. There remains no standard therapy for AT/RTs. Multimodal treatment strategies include a selective combination of conventional chemotherapy, high dose chemotherapy and stem cell rescue, intrathecal chemotherapy, and radiotherapy after tumor resection. The survival rate, even with aggressive treatment, is still low (2-year survival rate is 32.6%-44.6%). Moreover, currently used cytotoxic therapies incur some neurocognitive side effects, particularly in infants, highlighting the urgent need for novel targeted therapies.
Bortezomib (Velcade®) is the first generation proteasome inhibitor developed by Millennium Pharmaceuticals, Inc. as an anti-cancer medication. Bortezomib was approved by FDA for the treatment of adult patients with multiple myeloma and mantle cell lymphoma (newly diagnosed or relapse/recurrent disease). In children, the safety of BTZ has been proved in phase I clinical trial of patients with acute lymphoblastic leukemia, refractory or recurrent solid tumors, relapsed/refractory high-risk neuroblastoma. Recently, we found the proteasome-encoding genes were highly expressed in AT/RTs compared with that in normal brain tissues, correlated with the malignant phenotype of tumor cells, and were essential for tumor cell survival. Bortezomib targets proteostasis, inhibiting tumor growth and inducing apoptosis through p53 accumulation in three Myc-AT/RT cell lines and in mice with orthotopic xenografts of AT/RT. Our findings suggest that BTZ is a promising targeted therapy for Myc-AT/RTs (manuscript under review). To determine whether the other subgroups of ATRTs (i.e., SHH and TYR subgroups) are sensitive to BTZ, we conducted the in vivo drug test in 2 SHH-AT/RT cell lines (CHLA-02 and CHLA-04). Although CHLA-02 and CHLA-04 cell line were less sensitive to BTZ (IC50 of 15.1 (14.3-15.9) nM and 15.8 (14.5-17.3) nM, respectively) than Myc-AT/RT cell line (IC50 of 5.84 to 8.7 nM), these inhibitory concentrations are still clinically achievable (Cmax, 231.6-312.3 nM). Furthermore, the dependence on ubiquitin proteasome system for survival and high sensitivity to proteasome inhibitors have been reported in SMARCB1-deficient cancer cells. Additionally, we also observed the subgroup shifting in one infant with AT/RTs, from SHH subgroup of primary tumor to Tyr subgroup of the first recurrent tumor and Myc subgroup of the second recurrent tumor. Therefore, we hypothesize that BTZ treatment is potentially effective to all subgroups of CNS AT/RT and propose a clinical trial utilizing BTZ as an add-on therapy to standard and high-dose chemotherapy
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib single arm | Experimental | Drug: BortezomibBortezomib will be administered with chemotherapy on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 56-day treatment cycle for 4 cycles in newly diagnosed patients enrolled on Cohort 1. Bortezomib will be administered as a single agent on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day treatment cycle for 4 cycles in all recurrent patients enrolled on Cohort 2. |
Who may qualify
- Ages
- 1 year to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (27 listed)
- Patients with a valid Informed Consent Form signed by the Legal Guardian and/or Patient himself/herself.
- Patients with CNS AT/RT who were initially diagnosed at the age of 0-20 years.
- Disease Status:
- Cohort 1: Patients with newly diagnosed AT/RT; Cohort 2: Patients with recurrent or refractory CNS AT/RT who have had at least 1 line of chemotherapy with radiographically measurable disease as defined by at least 1 lesion that can be measured in 2 dimensions.
- Previous Anticancer Therapy:
Key exclusion criteria (15 listed)
- Clinically significant medical disorders that could compromise the ability to tolerate protocol therapy or that would interfere with the study procedures or results history.
- Presence of an active, uncontrolled infection.
- Existing peripheral neuropathy of NCI CTCAE v5.0 grade 2 or higher.
- Patients who have not recovered to baseline from previous treatment.
- Patients with hypersensitivity (not including local reactions) to BTZ, boron, or mannitol.
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 |
|---|---|---|
| Bortezomib4 cycles of Bortezomib treatment, with each cycle include 8 doses of Bortezomib at 1.3 mg/m2 | Drug | Bortezomib single arm |
Primary outcome
Overall Response Rate (ORR)
Time frame: through study completion, an average of 1 year
Overall Response Rate (ORR) to bortezomib in patients with recurrent or refractory CNS AT/RT.
2 secondary outcomes
Progression-Free Survival (PFS)
Time frame: through study completion, an average of 1 year
Overall Survival (OS)
Time frame: through study completion, an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2025.
- Derived from this study: PubMed 42745490Ho WL, Hsieh MY, Liao YM, Chiou SS, Shiah HS, Chiang CH, Jou ST, Yen HJ, Lee YY, Liang ML, Yeh TC, Chou YC, Huang FL, Chen SH, Lee HL, Kuo CC, Yang YS, Chen SM, Tsai ML, Chang H, Hsieh KL, Fang CL, Chang CY, Wang JL, Chen CC, Loh JK, Lin PC, Lin TC, Wang SC, Tu YF, Cheng CN, Chuang JM, Tran HM, Sung SY, Lai I, Wu KS, Miser JS, Liu YL, Wong TT. A Phase Ib Case Series Using Bortezomib With Chemotherapy in Atypical Teratoid/Rhabdoid Tumors. Cancer Med. 2026 Sep;15(9):e72173. doi: 10.1002/cam4.72173.
- Individual participant dataSharing planned: Undecided. Trial still conducted.
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib in people with Atypical Teratoid/Rhabdoid Tumors (AT/RTs) and Central Nervous System (CNS) Tumors, run by Taipei Medical University at 1 site in Taiwan.
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 27 inclusion and 15 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: under way, not looking for participants, as of the sponsor's last update on 28 Feb 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 Taiwan. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Overall Response Rate (ORR) (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06853080, which also lists 1 linked publication.
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 28 Feb 2025.