|No phase specified||Biomarker/Laboratory analysis, Treatment||Active||2 months to 3 years||NCI||NCI-2012-03167|
PBTC-026, U01CA081457, NCT00867178
This pilot clinical trial studies the side effects and the best way to give vorinostat with isotretinoin and combination chemotherapy and to see how well it works in treating younger patients with embryonal tumors of the central nervous system. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as isotretinoin, vincristine sulfate, cisplatin, cyclophosphamide, and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vorinostat with isotretinoin and combination chemotherapy may be and effective treatment for embryonal tumors of the central nervous system. A peripheral blood stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. This may allow more chemotherapy to be given so that more tumor cells are killed.
Further Study Information
I. To investigate the feasibility of administering vorinostat (SAHA) and isotretinoin for three days prior and concomitant with cisplatin based chemotherapy over three courses of induction chemotherapy.
II. To describe the toxicity of administering vorinostat (SAHA) and isotretinoin for three days prior and concomitant with cisplatin based chemotherapy over three courses of induction chemotherapy.
III. To investigate prognostic values of histopathological classification and biological markers in the context of a feasibility study.
I. To estimate the preliminary response rate of this approach in patients with measurable residual disease (primary site and/or metastatic sites).
II. To estimate disease specific progression-free and overall survival, in the context of a feasibility study.
III. To explore the predictive values of biological markers in cerebrospinal fluid (CSF), plasma, urine tumor material in the context of a feasibility study.
OUTLINE: This is a multicenter study.
INDUCTION THERAPY: Patients receive vorinostat orally (PO) once daily (QD) and isotretinoin PO twice daily (BID) on days 1-4; vincristine sulfate intravenously (IV) on days 4, 11, and 18; cisplatin IV over 6 hours on day 4; cyclophosphamide IV over 1 hour on days 5-6; and etoposide phosphate IV over 1 hour on days 4-6. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo peripheral blood stem cell (PBSC) harvesting after each course.
CONSOLIDATION THERAPY: Within 6 weeks (10 weeks if patient is re-staged) after completion of induction therapy, patients receive carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1-2. Patients also receive autologous PBSC rescue infusion over 6 hours on day 4. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3 weeks later, patients with M0 non-desmoplastic medulloblastoma also undergo conformal radiotherapy* to the tumor bed.
NOTE: *Patients with supratentorial primary tumors or metastatic disease undergo radiotherapy at the discretion of treating physician.
MAINTENANCE THERAPY: Beginning 4 weeks after completion of radiotherapy or immediately after completion of consolidation therapy, patients receive vorinostat PO QD on days 1, 3, 5, 6, 8, 10, 12, and 13 and isotretinoin PO BID on days 1-14. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.
- Patients must have a histologically confirmed, newly-diagnosed medulloblastoma (except for patients with the histology of localized (M0) desmoplastic medulloblastoma or atypical teratoid/rhabdoid tumor [ATRT]) or supratentorial primitive neuroectodermal tumor (PNET) including pineoblastomas
- Patients must have not received any prior therapy other than surgery and/or steroids
- Patient must have adequate pre-trial formalin-fixed, paraffin-embedded (FFPE) tumor material available for use in the biology studies and central pathology review; if snap frozen tissue is not available, the study chair must be contacted to discuss eligibility
- Patient must be a suitable candidate, by institutional standards for stem cell apheresis
- Lansky performance score (LPS for =< 16 years of age) >= 30 assessed within two weeks prior to registration
- No prior therapy except surgery and/or corticosteroids alone
- Absolute neutrophil count (ANC) >= 1000/ul (unsupported)
- Platelets >= 100,000/ul (unsupported)
- Hemoglobin >= 8 g/dL (may be supported)
- Bilirubin < 1.5 times upper limit of normal for age
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 1.5 times institutional upper limit of normal for age
- Serum creatinine =< 1.5 times upper limit of institutional normal for age or glomerular filtration rate (GFR) >= 70 ml/min/1.73m^2 or estimated GFR (Schwartz bedside) that is > 99ml/min/1.73m^2
- Parents/legal guardians must have the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines
- Patients with diagnosis of atypical teratoid/rhabdoid tumor (ATRT by histology, immunohistochemistry and/or molecular analysis) and desmoplastic M0 medulloblastoma will be excluded from the study
- Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results
- Patients receiving any other anticancer or investigational drug therapy are excluded; patients having taken valproic acid within 2 weeks prior to initiation of treatment are excluded
- Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
- Patients with a parabens allergy
Trial Lead Organizations/Sponsors
National Cancer Institute
|Sarah Leary||Principal Investigator|
|Children's Hospital Los Angeles|
|Girish Dhall||Ph: 323-361-4629|
|Girish Dhall||Principal Investigator|
|Lucile Packard Children's Hospital at Stanford University Medical Center|
|Paul G. Fisher||Ph: 650-721-5889|
|Paul Graham Fisher||Principal Investigator|
|District of Columbia|
|Children's National Medical Center|
|Lindsay B. Kilburn||Ph: 202-476-3854|
|Lindsay B. Kilburn||Principal Investigator|
|Ann and Robert H. Lurie Children's Hospital of Chicago|
|Stewart Goldman||Ph: 312-227-4844|
|Stewart Goldman||Principal Investigator|
|NCI - Pediatric Oncology Branch|
|Katherine E. Warren||Ph: 301-435-4683|
|Katherine Warren||Principal Investigator|
|Memorial Sloan-Kettering Cancer Center|
|Ira J. Dunkel||Ph: 212-639-2153|
|Ira J. Dunkel||Principal Investigator|
|Duke Cancer Institute|
|Sridharan Gururangan||Ph: 919-684-3506|
|Sri Gururangan||Principal Investigator|
|Cincinnati Children's Hospital Medical Center|
|Maryam Fouladi||Ph: 513-803-0721|
|Maryam Fouladi||Principal Investigator|
|Children's Hospital of Philadelphia|
|Peter C. Phillips||Ph: 215-590-2107|
|Peter C. Phillips||Principal Investigator|
|Children's Hospital of Pittsburgh of UPMC|
|Ian F. Pollack||Ph: 412-692-5881|
|Ian F. Pollack||Principal Investigator|
|St. Jude Children's Research Hospital|
|Alberto Broniscer||Ph: 901-595-4925|
|Alberto Broniscer||Principal Investigator|
|M. D. Anderson Cancer Center at University of Texas|
|Anita Mahajan||Ph: 713-563-2350|
|Anita Mahajan||Principal Investigator|
|Texas Children's Hospital|
|Murali M. Chintagumpala||Ph: 832-822-4266|
|Murali M. Chintagumpala||Principal Investigator|
|Children's Hospital and Regional Medical Center - Seattle|
|Sarah E. Leary||Ph: 206-987-2106|
|Sarah E. Leary||Principal Investigator|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00867178
ClinicalTrials.gov processed this data on January 21, 2014
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