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Clinical Study of Vorinostat in Combination With Etoposide in Pediatric Patients < 21 Years at Diagnosis With Refractory Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01294670
Recruitment Status : Active, not recruiting
First Posted : February 11, 2011
Last Update Posted : February 26, 2020
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
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
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE February 9, 2011
First Posted Date  ICMJE February 11, 2011
Last Update Posted Date February 26, 2020
Actual Study Start Date  ICMJE February 2011
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 10, 2011)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2011)
  • To evaluate the efficacy (CR (complete response) + PR (partial response) rate) [ Time Frame: 1 year ]
    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.
  • To evaluate the biologic effects using Histone Acetylation, Gene Expression Profiling, and Histone Phosphorylation Profiling. [ Time Frame: 2 years ]
    of the novel combination of vorinostat and etoposide in pediatric patients with refractory solid tumors including central nervous system tumors
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Study of Vorinostat in Combination With Etoposide in Pediatric Patients < 21 Years at Diagnosis With Refractory Solid Tumors
Official Title  ICMJE A Phase I/II Clinical Study of Vorinostat in Combination With Etoposide in Pediatric Patients < 21 Years at Diagnosis With Refractory Solid Tumors
Brief 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. 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumors
  • Relapsed/Refractory Sarcomas
Intervention  ICMJE Drug: Vorinostat and Etoposide
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 Arms  ICMJE Experimental: Vorinostat and Etoposide
This is a multi-center, open label, phase I/II trial of escalating doses of vorinostat in combination with etoposide.
Intervention: Drug: Vorinostat and Etoposide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 26, 2016)
27
Original Estimated Enrollment  ICMJE
 (submitted: February 10, 2011)
50
Estimated Study Completion Date  ICMJE February 2021
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • 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.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01294670
Other Study ID Numbers  ICMJE 10-096
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE
  • Merck Sharp & Dohme Corp.
  • 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
Investigators  ICMJE
Principal Investigator: Tanya Trippett, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP