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

NCT01294670 | Completed Phase 1 Results

• 1 other identifier: 10-096
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 11

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.

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.

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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

  1 year

Secondary Outcomes (2)

• To Evaluate the Efficacy (CR (Complete Response) + PR (Partial Response) Rate)

  1 year

• To Evaluate the Biologic Effects Using Histone Acetylation, Gene Expression Profiling, and Histone Phosphorylation Profiling.

  2 years

Study Arms (1)

Vorinostat and Etoposide

EXPERIMENTAL

This is a multi-center, open label, phase I/II trial of escalating doses of vorinostat in combination with etoposide.

Drug: Vorinostat and Etoposide

Interventions

Vorinostat and Etoposide DRUG

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.

Vorinostat and Etoposide

Eligibility Criteria

• Age: 4 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator
• Phoenix Children's Hospital: collaborator
• Milton S. Hershey Medical Center: collaborator
• Johns Hopkins University: collaborator
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: collaborator
• Children's Hospital Colorado: collaborator
• University of Florida: collaborator
• Alberta Children's Hospital: collaborator
• M.D. Anderson Cancer Center: collaborator
• Dana-Farber Cancer Institute: collaborator
• Children's Mercy Hospital Kansas City: collaborator
• Johns Hopkins All Children's Hospital: collaborator
• Arnold Palmer Hospital for Children: collaborator

Study Sites (11)

Phoenix Children'S Hospital

Phoenix, Arizona, 85016, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Arnold Palmer Hospital for Children/MD Anderson Cancer Center Orlando

Orlando, Florida, 32806, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

John Hopkins Medical Center

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Children's Mercy Hospital & Clinics

Kansas City, Missouri, 64108, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Pennsylvania State University College of Medicine

Hershey, Pennsylvania, 17110, United States

Location

Md Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Alberta Children'S Hospital

Calgary, Alberta, T2N 1N4, Canada

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Sarcoma

Interventions

Vorinostat; Etoposide

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Tanya Trippett, MD
• Organization: Memorial Sloan Kettering Cancer Center

trippet@mskcc.org

1-833-MSK-KIDS

Study Officials

• Tanya Trippett, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2011
• First Posted: February 11, 2011
• Study Start: February 9, 2011
• Primary Completion: December 8, 2020
• Study Completion: December 8, 2020
• Last Updated: November 18, 2021
• Results First Posted: November 18, 2021

Record last verified: 2020-12

Locations

US (10); CA (1)