Solid TumorsPhase 1/2NCT01294670
Clinical Study of Vorinostat in Combination With Etoposide in Pediatric Patients < 21 Years at Diagnosis With Refractory Solid Tumors
A Phase 1/2 study testing Vorinostat and Etoposide in people with Solid Tumors and Relapsed/Refractory Sarcomas, run by Memorial Sloan Kettering Cancer Center at 11 sites in 2 countries.
Trial summary
The purpose of this study is to find out how safe and effective treatment with a new combination of drugs, vorinostat and etoposide, is in treating cancer. The medication etoposide is a standard medication used in the treatment of cancer in children. Read more about this study
- Who is it for?
- Ages 4 to 21 years
- Conditions the study is for
- Solid Tumors, Relapsed/Refractory Sarcomas
- What is being tested?
- Vorinostat and Etoposide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 9 Feb 2011to 8 Dec 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 4 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Phase I Component: Histologic confirmation of relapsed/refractory solid tumors, including tumors of the central nervous system that have failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist. Patients with diffuse pontine glioma are not required to have histologic confirmation of disease, and are eligible with radiologic confirmation. Phase II Component: the population will be restricted to relapsed/refractory sarcomas
- Patient must be between 4-21 years of age at the time of study enrollment. Efforts will be made to enroll patients <13 years of age so that adequate information about the biologic effects of this agent in younger patients can be obtained.
- Patient must have Karnofsky > or = to 60% for patients >10 years of age; Lansky Play Scale > or = to to 60 for children < or = to 10 years of age
- Patient must have a life expectancy of > 8 weeks.
- There is no limit to the number of prior treatment regimens provided that performance status and life expectancy meet the criteria above.
- Absolute neutrophil count (ANC) ≥ 1000 / mcL
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- Platelets ≥100,000 / mcL (transfusion not permitted)
- Hemoglobin ≥ 9 g/dL qualifications (transfusion permitted)
- Coagulation Prothrombin Time or INR ≤ 1.5x upper limit of normal (ULN)
- Serum creatinine ≤ 1.5x upper limit of normal (ULN) OR calculated creatinine clearance ≥ 60 mL/min for patients with creatinine levels > 1.5x institutional ULN. or calculated creatinine clearance Creatinine clearance should be calculated per institutional standard.
- Serum total bilirubin ≤ 1.5 x ULN Patient's who don't meet this criteria must have a Direct bilirubin ≤ 1.5 x ULN
- AST (SGOT) and ALT (SGPT) Alkaline Phosphatase (liver fraction)
- ≤ 2.5 x ULN. If AST or ALT is > 2.5 x ULN, then the liver fraction of Alkaline Phosphatase should be ≤ 2.5 x ULN
- Phase I component: Patients may have measurable or non-measurable disease. Phase II component: Patients may only have measurable disease.
- Patient must have no persistent toxicities from prior therapy > or = to Grade 2 with the exception of hematologic indices (i.e. hemoglobin, WBC, ANC, ALC).
- For females of childbearing potential, a negative serum pregnancy test must be documented within 72 hours of receiving the first dose of vorinostat.
- Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent.
- Female patients of childbearing potential must be willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study, starting with visit 1.
- Male patients must agree to use an adequate method of contraception for the duration of the study.
- Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
- Myelosuppressive chemotherapy: At least 2 weeks must have elapsed since the administration of previous therapy. Six weeks must have elapsed since administration of nitrosoureas or mitomycin C. Seven days must have elapsed since the administration of G-CSF and/or GM-CSF.
- Biologic agents: At least 14 days must have elapsed since the completion of therapy with a biologic agent such as a monoclonal antibody. Seven days must have elapsed since the last dose of retinoids.
- Radiation therapy (XRT): > or = to 2 weeks must have elapsed for local XRT (small port); > or = to 6 months must have elapsed if prior radiation to > or = to 50% of the pelvis or if other substantial bone marrow irradiation, including total body irradiation.
- Patient must be able to swallow capsules.
- Patient must have an available archival/pre-treatment block or fresh tumor biopsy for molecular profiling to be performed.
Who cannot join
- A patient meeting any of the following criteria is not eligible to participate in this study:
- Patients currently participating or has participated in a study with an investigational compound or device within 4 weeks of initial dosing with study drugs.
- Patients with a prior history of treatment with HDAC inhibitors ( e.g. SNDX-275/entinostat, LAQ-824, LBH589, PXD-101/belinostat, etc). Patients who have received Valproic acid will be excluded from this study.
- Patients with non CNS primary tumors who have known brain metastases or symptomatic CNS disease (e.g. cranial nerve abnormalities) without cytologic abnormality in the CSF should be excluded from this clinical trial because of their poor prognosis and known propensity for the development of progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with metastatic CNS tumors will not be excluded from enrollment on this study in the phase I component only.
- Patients who have undergone prior autologous stem cell transplantation or allogeneic transplantation.
- Uncontrolled intercurrent illness or circumstances that could limit compliance with the study requirements including, but not limited to: ongoing or active bacterial or fungal infection, acute or chronic graft versus host disease, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations.
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- Patients who are pregnant or breastfeeding, or expecting to conceive within the projected duration of the study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat, lactating patients will be excluded from this study.
- Patients known to be Human Immunodeficiency Virus (HIV)-positive.
- Patients with known hypersensitivity to the components of the study drugs or their analogs.
- Patients with symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible.
- Patients who are at the time of signing informed consent, a regular user of any illicit drugs, substance abuser or who have a recent history of drug or alcohol abuse.
- Patients with a known history of Hepatitis B or C.
- Patients who have a history of gastrointestinal surgery or other procedures that might in the opinion of the investigator, interfere with the absorption or swallowing of the study drug.
- Patients who are unable to take or tolerate oral medications on a continuous basis.
- Patients with a history of a prior malignancy who have undergone potentially curative therapy with no evidence of that disease for five years or patients, who are deemed low risk for recurrence by his/her treating physician are permitted to enroll.
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States10 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
John Hopkins Medical Center
Baltimore, Maryland, 21287
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Pennsylvania State University College of Medicine
Hershey, Pennsylvania, 17110
Md Anderson Cancer Center
Houston, Texas, 77030
Children's Mercy Hospital & Clinics
Kansas City, Missouri, 64108
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Arnold Palmer Hospital for Children/MD Anderson Cancer Center Orlando
Orlando, Florida, 32806
Phoenix Children'S Hospital
Phoenix, Arizona, 85016
All Children's Hospital
St. Petersburg, Florida, 33701
About this study
Official title: A Phase I/II Clinical Study of Vorinostat in Combination With Etoposide in Pediatric Patients < 21 Years at Diagnosis With Refractory Solid Tumors
The purpose of this study is to find out how safe and effective treatment with a new combination of drugs, vorinostat and etoposide, is in treating cancer. The medication etoposide is a standard medication used in the treatment of cancer in children. Vorinostat is an experimental drug which targets a protein(s) that control the way cancer cells grow and divide. Vorinostat is approved by the FDA in adults with certain cancers but not approved yet in children.
There are two parts to this study. In the first part of this study, the phase I portion, a safe dose of the combination, vorinostat and etoposide. The goal of second part of this study, the phase II portion, is to see how effective the combination of vorinostat and etoposide is in treating cancer.
- Conditions
- Solid Tumors, Relapsed/Refractory Sarcomas
- Being tested
- Vorinostat and Etoposide
- Keywords
- ETOPOSIDE (VP-16), SAHA (SUBEROYLANILIDE HYDROXAMIC ACID) (Vorinostat), Pediatric, 10-096, POETIC, phase II component: the population will be restricted to relapsed/refractory sarcomas.
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vorinostat and EtoposideDrug
Patients will be assessed in 3-week cycles. Escalating doses of vorinostat will be administered orally on a daily x 4 schedule in combination with a fixed dose of etoposide. Etoposide will be administered intravenously daily x 3 days. Cohorts of 3-6 patients will be treated with vorinostat and etoposide. In the phase II component, patients will be treated at the RP2D established in the Phase I component of the study, which was found to be 270 mg/m2/dose of Vorinostat and 100 mg/m2/dose of Etoposide.
| Study group | Role | What they receive |
|---|---|---|
| Vorinostat and Etoposide | Experimental | This is a multi-center, open label, phase I/II trial of escalating doses of vorinostat in combination with etoposide. Receives: Drug: Vorinostat and Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Establish the Dose Limiting Toxicity (DLT)
of the novel combination vorinostat and etoposide in pediatric patients with refractory solid tumors including tumors of the central nervous system. The Toxicity will be evaluated according to NCI CTCAE Version 4.0.
Measured: Patients will be assessed in 3-week cycles.
To Establish the Maximum Tolerated Dose (MTD)
of the novel combination vorinostat and etoposide in pediatric patients with refractory solid tumors including tumors of the central nervous system.
Measured: 1 year
To Establish the Efficacy (CR (Complete Response) + PR (Partial Response) Rate)
of the novel combination vorinostat and etoposide in pediatric patients with relapsed/refractory sarcoma. Evaluation for response will be determined by Revised RECIST guideline
Measured: 1 year
Secondary outcomes (2)
To Evaluate the Efficacy (CR (Complete Response) + PR (Partial Response) Rate)
of the novel combination vorinostat and etoposide in pediatric patients enrolled in the phase I component of the study. Evaluation for response will be determined by Revised RECIST guideline.
Measured: 1 year
To Evaluate the Biologic Effects Using Histone Acetylation, Gene Expression Profiling, and Histone Phosphorylation Profiling.
of the novel combination of vorinostat and etoposide in pediatric patients with refractory solid tumors including central nervous system tumors
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2011 (estimated)
- Study start9 Feb 2011
- Primary completion8 Dec 2020
- Study completion8 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Phoenix Children's Hospital, Milton S. Hershey Medical Center, Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Children's Hospital Colorado, University of Florida, Alberta Children's Hospital, M.D. Anderson Cancer Center, Dana-Farber Cancer Institute, Children's Mercy Hospital Kansas City, Johns Hopkins All Children's Hospital, Arnold Palmer Hospital for Children
- Responsible party
- Sponsor
- Investigators
- Tanya Trippett, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01294670
- Sponsor's protocol ID
- 10-096
- Status last verified
- Dec 2020
- First submitted
- 9 Feb 2011
- Last updated
- 18 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Clinical Study of Vorinostat in Combination With Etoposide in Pediatric Patients < 21 Years at Diagnosis With Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT01294670
- Acronym / sponsor ID
- 10-096
- Conditions
- Solid Tumors, Relapsed/Refractory Sarcomas
- Keywords
- ETOPOSIDE (VP-16), SAHA (SUBEROYLANILIDE HYDROXAMIC ACID) (Vorinostat), Pediatric, 10-096, POETIC, phase II component: the population will be restricted to relapsed/refractory sarcomas.
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Phoenix Children's Hospital, Milton S. Hershey Medical Center, Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Children's Hospital Colorado, University of Florida, Alberta Children's Hospital, M.D. Anderson Cancer Center, Dana-Farber Cancer Institute, Children's Mercy Hospital Kansas City, Johns Hopkins All Children's Hospital, Arnold Palmer Hospital for Children
- Study start
- 9 Feb 2011 (actual)
- Primary completion
- 8 Dec 2020 (actual)
- Study completion
- 8 Dec 2020 (actual)
- First posted
- 11 Feb 2011 (estimated)
- Results
- Posted 18 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out how safe and effective treatment with a new combination of drugs, vorinostat and etoposide, is in treating cancer. The medication etoposide is a standard medication used in the treatment of cancer in children. Vorinostat is an experimental drug which targets a protein(s) that control the way cancer cells grow and divide. Vorinostat is approved by the FDA in adults with certain cancers but not approved yet in children.
There are two parts to this study. In the first part of this study, the phase I portion, a safe dose of the combination, vorinostat and etoposide. The goal of second part of this study, the phase II portion, is to see how effective the combination of vorinostat and etoposide is in treating cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vorinostat and Etoposide | Experimental | Drug: Vorinostat and EtoposideThis is a multi-center, open label, phase I/II trial of escalating doses of vorinostat in combination with etoposide. |
Who may qualify
- Ages
- 4 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (25 listed)
- Phase I Component: Histologic confirmation of relapsed/refractory solid tumors, including tumors of the central nervous system that have failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist. Patients with diffuse pontine glioma are not required to have histologic confirmation of disease, and are eligible with radiologic confirmation. Phase II Component: the population will be restricted to relapsed/refractory sarcomas
- Patient must be between 4-21 years of age at the time of study enrollment. Efforts will be made to enroll patients <13 years of age so that adequate information about the biologic effects of this agent in younger patients can be obtained.
- Patient must have Karnofsky > or = to 60% for patients >10 years of age; Lansky Play Scale > or = to to 60 for children < or = to 10 years of age
- Patient must have a life expectancy of > 8 weeks.
- There is no limit to the number of prior treatment regimens provided that performance status and life expectancy meet the criteria above.
Key exclusion criteria (15 listed)
- A patient meeting any of the following criteria is not eligible to participate in this study:
- Patients currently participating or has participated in a study with an investigational compound or device within 4 weeks of initial dosing with study drugs.
- Patients with a prior history of treatment with HDAC inhibitors ( e.g. SNDX-275/entinostat, LAQ-824, LBH589, PXD-101/belinostat, etc). Patients who have received Valproic acid will be excluded from this study.
- Patients with non CNS primary tumors who have known brain metastases or symptomatic CNS disease (e.g. cranial nerve abnormalities) without cytologic abnormality in the CSF should be excluded from this clinical trial because of their poor prognosis and known propensity for the development of progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with metastatic CNS tumors will not be excluded from enrollment on this study in the phase I component only.
- Patients who have undergone prior autologous stem cell transplantation or allogeneic transplantation.
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 |
|---|---|---|
| Vorinostat and EtoposidePatients will be assessed in 3-week cycles. Escalating doses of vorinostat will be administered orally on a daily x 4 schedule in combination with a fixed dose of etoposide. Etoposide will be administered intravenously daily x 3 days. Cohorts of 3-6 patients will be treated with vorinostat and etoposide. In the phase II component, patients will be treated at the RP2D established in the Phase I component of the study, which was found to be 270 mg/m2/dose of Vorinostat and 100 mg/m2/dose of Etoposide. | Drug | Vorinostat and Etoposide |
Primary outcome
To Establish the Dose Limiting Toxicity (DLT)
Time frame: Patients will be assessed in 3-week cycles.
of the novel combination vorinostat and etoposide in pediatric patients with refractory solid tumors including tumors of the central nervous system. The Toxicity will be evaluated according to NCI CTCAE Version 4.0.
To Establish the Maximum Tolerated Dose (MTD)
Time frame: 1 year
of the novel combination vorinostat and etoposide in pediatric patients with refractory solid tumors including tumors of the central nervous system.
To Establish the Efficacy (CR (Complete Response) + PR (Partial Response) Rate)
Time frame: 1 year
of the novel combination vorinostat and etoposide in pediatric patients with relapsed/refractory sarcoma. Evaluation for response will be determined by Revised RECIST guideline
2 secondary outcomes
To Evaluate the Efficacy (CR (Complete Response) + PR (Partial Response) Rate)
Time frame: 1 year
To Evaluate the Biologic Effects Using Histone Acetylation, Gene Expression Profiling, and Histone Phosphorylation Profiling.
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
Related trials for Solid Tumors
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Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
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IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
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Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm
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.
Tanya Trippett, MD principal investigator
Memorial Sloan Kettering Cancer Center
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Vorinostat and Etoposide in people with Solid Tumors and Relapsed/Refractory Sarcomas, run by Memorial Sloan Kettering Cancer Center at 11 sites in 2 countries.
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 25 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: finished, as of the sponsor's last update on 18 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Canada. 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 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.
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?
Yes. Results are posted in the registry (first posted 18 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
To Establish the Dose Limiting Toxicity (DLT) (time frame: Patients will be assessed in 3-week cycles.). The study lists 3 primary outcomes in all. 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 18 Nov 2021.