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Clinical Trial Name - Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory So
| Original Study ID : CDR0000440999 |
| Secondary ID : Array |
| NCT ID : NCT00217412 |
| Brief Title : Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia |
| Official Title : A Phase I Study of SAHA (NSC#: 701852 IND#: 71976) in Pediatric Patients With Recurrent or Refractory Solid Tumors (Including Lymphomas) and Leukemia Followed By a Phase I Study of SAHA in Combination With 13-Cis-Retinoic Acid for Patients With Selected Recurrent/Refractory Solid Tumors |
| Brief Summary : RATIONALE: Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Isotretinoin may cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving vorinostat together with isotretinoin may be an effective treatment for cancer. PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with isotretinoin in treating young patients with recurrent or refractory solid tumors, lymphoma, or leukemia. |
| Source : National Cancer Institute (NCI) |
| Detailed Description : OBJECTIVES: Primary - Determine the maximum tolerated dose (MTD) of vorinostat (SAHA) in young patients with recurrent or refractory solid tumors or lymphomas. - Determine the MTD of SAHA administered in combination with isotretinoin in young patients with recurrent or refractory neuroblastoma, medulloblastoma/CNS primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor. - Determine the tolerability of the solid tumor MTD of SAHA in young patients with recurrent or refractory leukemia. - Determine the toxic effects of SAHA administered with or without isotretinoin in these patients. - Determine the pharmacokinetics of this drug in these patients. Secondary - Determine, preliminarily, the antitumor activity of SAHA administered with or without isotretinoin in these patients. - Correlate the pharmacokinetics of this drug with genetic polymorphisms (e.g., UGT1A1) in these patients. OUTLINE: This is a multicenter, dose-escalation study of vorinostat (SAHA). - Group 1 (solid tumor or lymphoma patients): Patients receive oral SAHA once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients may be treated at the MTD. - Group 2 (leukemia patients): Patients receive SAHA as in group 1 at the MTD. - Group 3 (select solid tumor patients): Patients receive oral isotretinoin twice daily on days 1-14. Patients also receive SAHA once daily on days 1-28 OR once on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. The MTD of SAHA is determined as in group 1. An additional 6 patients may be treated at the MTD. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A maximum of 60 patients will be accrued for this study. |
| Overall Status : Active, not recruiting |
| Start Date : August 2005 |
| Official Title : Phase 1 |
| Phase : Interventional |
| Study Design : Treatment |
| Enrollment : 60 |
| Verification Date : May 2008 |
| First Received Date : September 20, 2005 |
| Trial Eligibility |
| Criteria : DISEASE CHARACTERISTICS: - Histologically confirmed* diagnosis of 1 of the following: - Recurrent or refractory solid tumor or lymphoma (for patients in group 1) - Measurable or evaluable disease - Recurrent or refractory leukemia (for patients in group 2) - Greater than 25% blasts in the bone marrow (i.e., M3 bone marrow) - Active extramedullary disease allowed except leptomeningeal disease - Recurrent or refractory CNS tumor of 1 of the following types (for patients in group 3): - Neuroblastoma - Medulloblastoma/CNS primitive neuroectodermal tumor - Atypical teratoid rhabdoid tumor NOTE: *Histologic confirmation not required for intrinsic brain stem tumors - No known curative therapy or therapy proven to prolong survival with an acceptable quality of life exists - No bone marrow involvement by disease (for patients in groups 1 and 3) - No active CNS leukemia PATIENT CHARACTERISTICS: Age - 1 to 21 Performance status - Lansky 50-100% (for patients ≤ 10 years of age) - Karnofsky 60-100% (for patients > 10 years of age) Life expectancy - Not specified Hematopoietic - Absolute neutrophil count ≥ 1,000/mm^3 (for solid tumor patients) - Platelet count ≥ 100,000/mm^3* (for solid tumor patients) (20,000/mm^3** for leukemia patients) - Hemoglobin ≥ 8.0 g/dL (RBC transfusion allowed) (for solid tumor and leukemia patients) - Triglycerides < 300 mg/dL (for patients in group 3) NOTE: *Transfusion independent NOTE: **Transfusion allowed Hepatic - Bilirubin ≤ 1.5 times upper limit of normal (ULN) - ALT ≤ 5 times ULN - Albumin ≥ 2 g/dL Renal - Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR - Creatinine based on age as follows: - No greater than 0.8 mg/dL (for patients ≤ 5 years of age) - No greater than 1.0 mg/dL (for patients 6 to 10 years of age) - No greater than 1.2 mg/dL (for patients 11 to 15 years of age) - No greater than 1.5 mg/dL (for patients over 15 years of age) - Negative dipstick for protein OR < 1,000 mg protein/24 hour urine collection (for patients in group 3) - No evidence of gross hematuria (for patients in group 3) Other - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - Body surface area ≥ 0.5 m^2 - Neurologic deficits in patients with CNS tumors must be stable for ≥ 1 week before study entry - Able to swallow whole capsules - No uncontrolled infection - Skin toxicity < grade 1 (for patients in group 3) PRIOR CONCURRENT THERAPY: Biologic therapy - Recovered from prior immunotherapy - At least 7 days since prior hematopoietic growth factors - At least 7 days since prior antineoplastic biologic agents - At least 2 months since prior stem cell transplantation or rescue - No evidence of active graft-versus-host disease - No other concurrent biologic therapy or immunotherapy Chemotherapy - More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered - No concurrent chemotherapy Endocrine therapy - Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for ≥ 7 days prior to study entry - No concurrent dexamethasone for antinausea or antiemetic therapy Radiotherapy - Recovered from prior radiotherapy - At least 2 weeks since prior local, palliative, small-port radiotherapy - At least 3 months since prior total-body irradiation, radiotherapy to the craniospinal area, or radiotherapy to ≥ 50% of the pelvis - At least 6 weeks since other prior substantial radiotherapy to the bone marrow - No concurrent radiotherapy Surgery - Not specified Other - At least 2 weeks since prior valproic acid - No other concurrent investigational agents - No other concurrent anticancer therapy - No concurrent enzyme-inducing anticonvulsants |
| Gender : Both |
| Minimum Age : 1 Year |
| Maximum Age : 21 Years |
| Healthy Volunteers : No |
| Facilities |
| Facility Name : Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham |
| City : Birmingham |
| State : Alabama |
| Zip Code : 35294 |
| Country : United States |
| Facility Name : Children's Hospital of Orange County |
| City : Orange |
| State : California |
| Zip Code : 92868 |
| Country : United States |
| Facility Name : Stanford Cancer Center |
| City : Stanford |
| State : California |
| Zip Code : 94305-5824 |
| Country : United States |
| Facility Name : Children's National Medical Center |
| City : Washington |
| State : District of Columbia |
| Zip Code : 20010-2970 |
| Country : United States |
| Facility Name : Children's Memorial Hospital - Chicago |
| City : Chicago |
| State : Illinois |
| Zip Code : 60614 |
| Country : United States |
| Facility Name : Indiana University Melvin and Bren Simon Cancer Center |
| City : Indianapolis |
| State : Indiana |
| Zip Code : 46202-5289 |
| Country : United States |
| Facility Name : Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute |
| City : Boston |
| State : Massachusetts |
| Zip Code : 02115 |
| Country : United States |
| Facility Name : C.S. Mott Children's Hospital at University of Michigan Medical Center |
| City : Ann Arbor |
| State : Michigan |
| Zip Code : 48109-0286 |
| Country : United States |
| Facility Name : Mayo Clinic Cancer Center |
| City : Rochester |
| State : Minnesota |
| Zip Code : 55905 |
| Country : United States |
| Facility Name : University of Minnesota Cancer Center |
| City : Minneapolis |
| State : Minnesota |
| Zip Code : 55455 |
| Country : United States |
| Facility Name : Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - Saint Louis |
| City : St. Louis |
| State : Missouri |
| Zip Code : 63110 |
| Country : United States |
| Facility Name : Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center |
| City : New York |
| State : New York |
| Zip Code : 10032 |
| Country : United States |
| Facility Name : SUNY Upstate Medical University Hospital |
| City : Syracuse |
| State : New York |
| Zip Code : 13210 |
| Country : United States |
| Facility Name : Cincinnati Children's Hospital Medical Center |
| City : Cincinnati |
| State : Ohio |
| Zip Code : 45229-3039 |
| Country : United States |
| Facility Name : Oregon Health and Science University Cancer Institute |
| City : Portland |
| State : Oregon |
| Zip Code : 97239-3098 |
| Country : United States |
| Facility Name : Children's Hospital of Philadelphia |
| City : Philadelphia |
| State : Pennsylvania |
| Zip Code : 19104-9786 |
| Country : United States |
| Facility Name : St. Jude Children's Research Hospital |
| City : Memphis |
| State : Tennessee |
| Zip Code : 38105 |
| Country : United States |
| Facility Name : Baylor University Medical Center - Houston |
| City : Houston |
| State : Texas |
| Zip Code : 77030-2399 |
| Country : United States |
| Facility Name : Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas |
| City : Dallas |
| State : Texas |
| Zip Code : 75390 |
| Country : United States |
| Facility Name : Children's Hospital and Regional Medical Center - Seattle |
| City : Seattle |
| State : Washington |
| Zip Code : 98105 |
| Country : United States |
| Facility Name : Hospital for Sick Children |
| City : Toronto |
| State : Ontario |
| Zip Code : M5G 1X8 |
| Country : Canada |
| Facility Name : Hopital Sainte Justine |
| City : Montreal |
| State : Quebec |
| Zip Code : H3T 1C5 |
| Country : Canada |
| Interventions |
| Type : Drug |
| Name : isotretinoin |
| Type : Drug |
| Name : vorinostat |
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