DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



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

Information source: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Solid Tumors; Relapsed/Refractory Sarcomas

Intervention: Vorinostat and Etoposide (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Memorial Sloan Kettering Cancer Center

Official(s) and/or principal investigator(s):
Tanya Trippett, MD, Principal Investigator, Affiliation: Memorial Sloan Kettering Cancer Center

Overall contact:
Tanya Trippett,, MD, Phone: 212-639-8267

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.

Clinical Details

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

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

To establish the Dose Limiting Toxicity (DLT)

To establish the Maximum Tolerated Dose (MTD)

To establish the efficacy (CR (Complete Response) + PR (Partial Response) rate)

Secondary outcome:

To evaluate the efficacy (CR (complete response) + PR (partial response) rate)

To evaluate the biologic effects using Histone Acetylation, Gene Expression Profiling, and Histone Phosphorylation Profiling.

Eligibility

Minimum age: 4 Years. Maximum age: 21 Years. Gender(s): Both.

Criteria:

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.

Locations and Contacts

Tanya Trippett,, MD, Phone: 212-639-8267

Alberta Children'S Hospital, Calgary, Alberta T2N 1N4, Canada; Not yet recruiting
Tony Truong, MD, Phone: 403 955-2946
Tony Truong, MD, Principal Investigator

Phoenix Children'S Hospital, Phoenix, Arizona 85016, United States; Not yet recruiting
Jessica Boklan, MD, Phone: 602-546-0920
Jessica Boklan, MD, Principal Investigator

Children's Hospital Colorado, Aurora, Colorado 80045, United States; Recruiting
Lia Gore, MD, Phone: 720-777-4159
Lia Gore, MD, Principal Investigator

Arnold Palmer Hospital for Children/MD Anderson Cancer Center Orlando, Orlando, Florida 32806, United States; Recruiting
Amy Smith, MD, Phone: 321-841-8588
Amy Smith, MD, Principal Investigator

All Children's Hospital, St. Petersburg, Florida 33701, United States; Recruiting
Gregory Hale, MD, Phone: 727-767-4176
Gregory Hale, MD, Principal Investigator

John Hopkins Medical Center, Baltimore, Maryland 21287, United States; Not yet recruiting
Patrick Brown, MD, Phone: 410-614-4915
Patrick Brown, MD, Principal Investigator

Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States; Recruiting
Suzanne Shusterman, MD, Phone: 617-632-4901
Suzanne Shusterman, MD, Principal Investigator

Children's Mercy Hospital & Clinics, Kansas City, Missouri 64108, United States; Recruiting
Kathleen Neville, MD, Phone: 816-234-3059
Kathleen Neville, MD, Principal Investigator

Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States; Recruiting
Tanya Trippett, MD, Phone: 212-639-8267
Christine Pratilas, MD, Phone: 212-639-3964
Tanya Trippett, MD, Principal Investigator

Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17110, United States; Recruiting
Lisa McGregor, MD, Phone: 717-531-6012
Lisa McGregor, MD, Principal Investigator

Md Anderson Cancer Center, Houston, Texas 77030, United States; Not yet recruiting
Cynthia Herzog, MD
Cynthia Herzog, MD, Principal Investigator

Additional Information

Memorial Sloan Kettering Cancer Center

Starting date: February 2011
Last updated: April 28, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017