Ewing SarcomaPhase 1NYMC195NCT04308330
Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies
A Phase 1 study testing Vorinostat in people with Ewing Sarcoma and Rhabdomyosarcoma, run by New York Medical College at 1 site in United States.
Trial summary
Investigators are testing new experimental drug combinations such as the combination of vorinostat, vincristine, irinotecan, and temozolomide in the hopes of finding a drug that may be effective against tumors that have come back or that have not responded to standard therapy. Read more about this study
- Who is it for?
- Ages 1 year to 30 years
- Conditions the study is for
- Ewing Sarcoma, Rhabdomyosarcoma, Wilms Tumor
- What is being tested?
- Vorinostat
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Mar 2017to 31 Dec 2027
- Phase
- Phase 1
- 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 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: Patients must be less than or equal to 1 year and less than or equal to 30 years of age at initiation of protocol therapy.
- Diagnosis: Patients must have a confirmed histologic diagnosis of a relapsed or refractory solid tumor or CNS malignancy.
- Performance status: Patients over 16 years of age must have a Karnofsky score greater than or equal to 50. Children under 16 years of age must have a Lansky score greater than or equal to 50.
- Prior therapy: Patients may have received prior therapy with vincristine, irinotecan, or temozolomide. They may not however have received therapy that included a treatment cassette of irinotecan and temozolomide in combination.
- Prior myelosuppressive therapy: Patients must have not received myelosuppressive therapy in 3 weeks or nitrosourea chemotherapy within 6 weeks of initiation of protocol therapy.
- Hematologic growth factor support: Patients may not have received G-CSF within the previous 3 days or peg-filgrastim within the past 7 days.
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- Biologic anti-neoplastic therapy: At least 21 days or 5 half-lives (whichever is of longer duration) must have elapsed since the last administration of biologic antineoplastic therapy.
- Radiation therapy: ≥ 14 days since the last dose of local XRT; ≥ 6 months must have elapsed if prior TBI, craniospinal XRT or ≥ 50% radiation of pelvis; ≥ 6 wks must have elapsed if other substantial BM radiation.
- Autologous or allogeneic stem cell transplant: No active graft vs. host disease or need for immunosuppressive therapy. At least 3 months must have passed since neutrophil engraftment.
- Organ function:
- Bone marrow function:
- Peripheral absolute neutrophil count (ANC) greater than or equal to 1000 cells/mcL.
- Platelet count greater than or equal to100,000/mcL and no platelet transfusion within prior 7 days.
- Hemoglobin greater than or equal to 8 gm/dL
- Patients with known bone marrow metastatic disease may enroll on the study if they have a peripheral ANC greater than or equal to 750 cells/mcL. They will not be evaluable for hematologic toxicity.
- Adequate liver function:
- Total bilirubin less than or equal to 1.5x upper limit of normal (ULN) for age.
- SGPT (ALT) less than or equal to 5x ULN
- Serum albumin greater than or equal to 2 gm/dL
- Adequate renal function:
- Creatinine clearance or glomerular filtration rate >70 ml/min/1.73 m2 or a serum creatinine based on age and gender as follows:
- Age Maximum serum creatinine concentration (mg/dL) Male Female 1-<2 years 0.6 0.6 2-<6 years 0.8 0.8 6-<10 years 1 1 10-<13 years 1.2 1.2 13-<16 years 1.5 1.4 greater than or equal to 16 years 1.7 1.4 The threshold creatinine values in this table were derived from the Schwartz formula to estimate glomerular filtration rates (Schwartz et al. J. Peds. 106; 522. 1985) using child length and stature data from the CDC.
- Informed consent: All patients less than 18 years of age must sign a written informed consent. For patients <18 years of age, a parent or guardian must sign a written informed consent, unless the patient is an emancipated minor. Childhood assent, when appropriate, should be obtained as well per institutional guidelines.
Who cannot join
- Pregnancy or breast feeding: Women who are pregnant or breast feeding will not be entered on the protocol due to the risks of fetal and teratogenic adverse events with the therapeutic agents used in the protocol therapy.
- Corticosteroid use: Patients with CNS tumors who have not been on a stable or decreasing dose of corticosteroids for the 7 days prior to the initiation of protocol therapy.
- Antineoplastic therapy: Patients receiving any other antineoplastic therapy.
- Medication allergy:
- Allergy or intolerance to any of the protocol agents: vincristine, irinotecan, temozolomide, or vorinostat.
- Allergy or intolerance to cephalosporins.
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- Infection: Patients who have any uncontrolled infection, positive blood culture within 48 hours prior to protocol entry, or diagnosed or receiving therapy for Clostridium difficile infection.
- Patients may not have taken valproic acid or any other histone deacetylase inhibitor for at least 2 weeks prior to study enrollment.
- Children with neurofibromastosis Type 1, if being used for treatment of a low grade glioma.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
New York Medical College
Valhalla, New York, 10595
Harshini Mahanti, BS
Jeremy Rosenblum, MD
About this study
Official title: A Phase I Study of Vorinostat in Combination With Vincristine, Irinotecan, and Temozolomide in Children, Adolescents, and Young Adults With Relapsed or Refractory Solid Tumors and CNS Malignancies
Investigators are testing new experimental drug combinations such as the combination of vorinostat, vincristine, irinotecan, and temozolomide in the hopes of finding a drug that may be effective against tumors that have come back or that have not responded to standard therapy.
The goals of this study are:
- To find the highest safe dose of vorinostat that can be given together with vincristine, irinotecan, and temozolomide without causing severe side effects;
- To learn what kind of side effects this four drug combination can cause;
- To learn about the effects of vorinostat and the combination of vorinostat, vincristine, irinotecan, and temozolomide on specific molecules in tumor cells;
- To determine whether the combination of vorinosat, vincristine, irinotecan, and temozolomide is a beneficial treatment.
Read the detailed description
This first cycle will be used to determine whether the patient can tolerate the chemotherapeutic backbone without developing a DLT. The baseline disease evaluation will be obtained following hematologic recovery from the first cycle of chemotherapy, after which combination therapy with vorinostat will be given in subsequent cycles (2-12) w/ modifications if needed. Vorinostat dose escalation in subsequent patient cohorts will occur based on DLT to determine a MTD.
- Conditions
- Ewing Sarcoma, Rhabdomyosarcoma, Wilms Tumor, Neuroblastoma, Hepatoblastoma, Germ Cell Tumor
- Being tested
- Vorinostat
- Medical subject headings
- Sarcoma, Ewing, Rhabdomyosarcoma, Wilms Tumor, Neuroblastoma, Hepatoblastoma, Neoplasms, Germ Cell and Embryonal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorinostatDrug
Also called Zolinza
This is a phase I study of the combination of four drugs: vorinostat, vincristine, irinotecan, and temozolomide. This is called a Phase I study because the goal is to find the highest dose of vorinostat that investigators can give safely when it is used together with the chemotherapy drugs vincristine, irinotecan and temozolomide. Investigators are using vorinostat because it seems to work against cancer in test tubes and animals. It may be most effective when it is given with chemotherapy. The combination of these three agents together has never been given to children. Vincristine, irinotecan, and temozolomide are approved and used for the treatment of other types of cancer in adults and children. Vorinostat is approved and used to treat cancer in adults. The combination of these four drugs together is experimental. Investigators do not know if this combination of medicines will work in people. There is a lot that investigators do not yet know about this combination of medicines.
| Study group | Role | What they receive |
|---|---|---|
| Vorinostat | Experimental | The first cycle of chemotherapy will not include the experimental agent vorinostat. This first cycle will be used to determine whether the patient can tolerate the chemotherapeutic backbone without developing a DLT.
Cycle 1
* Vincristine: 1.5 mg/m2/day (maximum dose 2 mg) IV Days 1 and 8 over 1-15 minutes.
* Temozolomide: 125 mg/m2/day PO Days 1-5.
* Irinotecan: 50 mg/m2/day IV Days 1-5 over 60 minutes.
* Cefixime: 8 mg/kg/day (maximum dose 400 mg) PO. Begin 2 days prior to irinotecan therapy and continue through Day 8.
Cycles 2-12
* Vincristine: 1.5 mg/m2/day (maximum dose 2 mg) IV Days 1 and 8 over 1-15 minutes.
* Temozolomide: 125 mg/m2/day PO Days 1-5.
* Irinotecan: 50 mg/m2/day IV Days 1-5 over 60 minutes.
* Cefixime: 8 mg/kg/day (maximum dose 400 mg) PO. Begin 2 days prior to irinotecan therapy and continue through Day 8.
* Vorinostat: Dose per escalation schema daily Days 1-5.
* Vorinostat will not be administered during Cycle 1. Receives: Drug: Vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine a maximally tolerated (or optimal) dose of vorinostat
A minimum of 3 evaluable patients will be entered at each dose level. If no significant dose limiting toxicity is discovered, a maximum of 3 dose levels will be evaluated. The minimum patient enrollment will be 3 patients. Many of the patients enrolled on this trial are expected to be heavily pretreated. All patients will be given a VIT only "window" to evaluate adequate bone marrow reserve to tolerate protocol therapy. We expect that at most 20% of patients will not be able to tolerate VIT or VIT with dose reduced temozolomide. A maximum of 24 patients enrolled on study is anticipated. Once the MTD has been defined, up to 6 additional patients may be enrolled to acquire additional safety data regarding this combination of agents.
Measured: 1 year
Secondary outcomes (1)
Overall response rate (ORR) after therapy
To determine the overall response rate (ORR) of vorinostat in combination with VIT in children, adolescents, and young adults with relapsed or refractory solid tumors.
The overall (CR+PR) and best response rates with the 95% confidence intervals will be estimated based on the exact binomial distribution.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2020
- Study start17 Mar 2017
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ewing SarcomaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New York Medical College
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeremy Rosenblum, MD, Principal investigator, New York Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04308330
- Sponsor's protocol ID
- 12011
- Acronym
- NYMC195
- Status last verified
- Apr 2026
- First submitted
- 11 Mar 2020
- Last updated
- 15 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Vorinostat in Combination With Vincristine, Irinotecan, and Temozolomide in Children, Adolescents, and Young Adults With Relapsed or Refractory Solid Tumors and CNS Malignancies
- ClinicalTrials.gov ID
- NCT04308330
- Acronym / sponsor ID
- NYMC195 / 12011
- Conditions
- Ewing Sarcoma, Rhabdomyosarcoma, Wilms Tumor, Neuroblastoma, Hepatoblastoma, Germ Cell Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- New York Medical CollegeUniversity, hospital or other
- Study start
- 17 Mar 2017 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 16 Mar 2020 (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.
Investigators are testing new experimental drug combinations such as the combination of vorinostat, vincristine, irinotecan, and temozolomide in the hopes of finding a drug that may be effective against tumors that have come back or that have not responded to standard therapy.
The goals of this study are:
- To find the highest safe dose of vorinostat that can be given together with vincristine, irinotecan, and temozolomide without causing severe side effects;
- To learn what kind of side effects this four drug combination can cause;
- To learn about the effects of vorinostat and the combination of vorinostat, vincristine, irinotecan, and temozolomide on specific molecules in tumor cells;
- To determine whether the combination of vorinosat, vincristine, irinotecan, and temozolomide is a beneficial treatment.
Detailed description
This first cycle will be used to determine whether the patient can tolerate the chemotherapeutic backbone without developing a DLT. The baseline disease evaluation will be obtained following hematologic recovery from the first cycle of chemotherapy, after which combination therapy with vorinostat will be given in subsequent cycles (2-12) w/ modifications if needed. Vorinostat dose escalation in subsequent patient cohorts will occur based on DLT to determine a MTD.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vorinostat | Experimental | Drug: VorinostatThe first cycle of chemotherapy will not include the experimental agent vorinostat. This first cycle will be used to determine whether the patient can tolerate the chemotherapeutic backbone without developing a DLT. Cycle 1 * Vincristine: 1.5 mg/m2/day (maximum dose 2 mg) IV Days 1 and 8 over 1-15 minutes. * Temozolomide: 125 mg/m2/day PO Days 1-5. * Irinotecan: 50 mg/m2/day IV Days 1-5 over 60 minutes. * Cefixime: 8 mg/kg/day (maximum dose 400 mg) PO. Begin 2 days prior to irinotecan therapy and continue through Day 8. Cycles 2-12 * Vincristine: 1.5 mg/m2/day (maximum dose 2 mg) IV Days 1 and 8 over 1-15 minutes. * Temozolomide: 125 mg/m2/day PO Days 1-5. * Irinotecan: 50 mg/m2/day IV Days 1-5 over 60 minutes. * Cefixime: 8 mg/kg/day (maximum dose 400 mg) PO. Begin 2 days prior to irinotecan therapy and continue through Day 8. * Vorinostat: Dose per escalation schema daily Days 1-5. * Vorinostat will not be administered during Cycle 1. |
Who may qualify
- Ages
- 1 year to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (23 listed)
- Age: Patients must be less than or equal to 1 year and less than or equal to 30 years of age at initiation of protocol therapy.
- Diagnosis: Patients must have a confirmed histologic diagnosis of a relapsed or refractory solid tumor or CNS malignancy.
- Performance status: Patients over 16 years of age must have a Karnofsky score greater than or equal to 50. Children under 16 years of age must have a Lansky score greater than or equal to 50.
- Prior therapy: Patients may have received prior therapy with vincristine, irinotecan, or temozolomide. They may not however have received therapy that included a treatment cassette of irinotecan and temozolomide in combination.
- Organ function:
Key exclusion criteria (9 listed)
- Pregnancy or breast feeding: Women who are pregnant or breast feeding will not be entered on the protocol due to the risks of fetal and teratogenic adverse events with the therapeutic agents used in the protocol therapy.
- Corticosteroid use: Patients with CNS tumors who have not been on a stable or decreasing dose of corticosteroids for the 7 days prior to the initiation of protocol therapy.
- Antineoplastic therapy: Patients receiving any other antineoplastic therapy.
- Medication allergy:
- Allergy or intolerance to any of the protocol agents: vincristine, irinotecan, temozolomide, or vorinostat.
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 |
|---|---|---|
| VorinostatAlso: ZolinzaThis is a phase I study of the combination of four drugs: vorinostat, vincristine, irinotecan, and temozolomide. This is called a Phase I study because the goal is to find the highest dose of vorinostat that investigators can give safely when it is used together with the chemotherapy drugs vincristine, irinotecan and temozolomide. Investigators are using vorinostat because it seems to work against cancer in test tubes and animals. It may be most effective when it is given with chemotherapy. The combination of these three agents together has never been given to children. Vincristine, irinotecan, and temozolomide are approved and used for the treatment of other types of cancer in adults and children. Vorinostat is approved and used to treat cancer in adults. The combination of these four drugs together is experimental. Investigators do not know if this combination of medicines will work in people. There is a lot that investigators do not yet know about this combination of medicines. | Drug | Vorinostat |
Primary outcome
To determine a maximally tolerated (or optimal) dose of vorinostat
Time frame: 1 year
A minimum of 3 evaluable patients will be entered at each dose level. If no significant dose limiting toxicity is discovered, a maximum of 3 dose levels will be evaluated. The minimum patient enrollment will be 3 patients. Many of the patients enrolled on this trial are expected to be heavily pretreated. All patients will be given a VIT only "window" to evaluate adequate bone marrow reserve to tolerate protocol therapy. We expect that at most 20% of patients will not be able to tolerate VIT or VIT with dose reduced temozolomide. A maximum of 24 patients enrolled on study is anticipated. Once the MTD has been defined, up to 6 additional patients may be enrolled to acquire additional safety data regarding this combination of agents.
1 secondary outcome
Overall response rate (ORR) after therapy
Time frame: 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 15 Apr 2026.
- 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.
Jeremy Rosenblum, MD principal investigator
New York Medical College
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vorinostat in people with Ewing Sarcoma and Rhabdomyosarcoma, run by New York Medical College at 1 site in United States.
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 23 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 15 Apr 2026. 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 United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Contact Harshini Mahanti, BS (914-594-2143, harshini_mahanti@nymc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine a maximally tolerated (or optimal) dose of vorinostat (time frame: 1 year). 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 15 Apr 2026.