Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies

Introduction

• Org Study ID: 12011
• NTC ID: NCT04308330
• Lead Sponsor Name: New York Medical College
• Status: RECRUITING

Conditions

• Wilms Tumor

Brief Summary

Investigators are testing new experimental drug combinations such as the combination of vorinostat, vincristine, irinotecan, and temozolomide in the hopes of finding a drug that may be effective against tumors that have come back or that have not responded to standard therapy.

The goals of this study are:

* To find the highest safe dose of vorinostat that can be given together with vincristine, irinotecan, and temozolomide without causing severe side effects;
* To learn what kind of side effects this four drug combination can cause;
* To learn about the effects of vorinostat and the combination of vorinostat, vincristine, irinotecan, and temozolomide on specific molecules in tumor cells;
* To determine whether the combination of vorinosat, vincristine, irinotecan, and temozolomide is a beneficial treatment.

Eligibility Criteria

Inclusion Criteria:

* Age: Patients must be less than or equal to 1 year and less than or equal to 30 years of age at initiation of protocol therapy.
* Diagnosis: Patients must have a confirmed histologic diagnosis of a relapsed or refractory solid tumor or CNS malignancy.
* Performance status: Patients over 16 years of age must have a Karnofsky score greater than or equal to 50. Children under 16 years of age must have a Lansky score greater than or equal to 50.
* Prior therapy: Patients may have received prior therapy with vincristine, irinotecan, or temozolomide. They may not however have received therapy that included a treatment cassette of irinotecan and temozolomide in combination.

* Prior myelosuppressive therapy: Patients must have not received myelosuppressive therapy in 3 weeks or nitrosourea chemotherapy within 6 weeks of initiation of protocol therapy.
* Hematologic growth factor support: Patients may not have received G-CSF within the previous 3 days or peg-filgrastim within the past 7 days.
* Biologic anti-neoplastic therapy: At least 21 days or 5 half-lives (whichever is of longer duration) must have elapsed since the last administration of biologic antineoplastic therapy.
* Radiation therapy: ≥ 14 days since the last dose of local XRT; ≥ 6 months must have elapsed if prior TBI, craniospinal XRT or ≥ 50% radiation of pelvis; ≥ 6 wks must have elapsed if other substantial BM radiation.
* Autologous or allogeneic stem cell transplant: No active graft vs. host disease or need for immunosuppressive therapy. At least 3 months must have passed since neutrophil engraftment.
* Organ function:

Bone marrow function:

* Peripheral absolute neutrophil count (ANC) greater than or equal to 1000 cells/mcL.
* Platelet count greater than or equal to100,000/mcL and no platelet transfusion within prior 7 days.
* Hemoglobin greater than or equal to 8 gm/dL
* Patients with known bone marrow metastatic disease may enroll on the study if they have a peripheral ANC greater than or equal to 750 cells/mcL. They will not be evaluable for hematologic toxicity.

- Adequate liver function:
* Total bilirubin less than or equal to 1.5x upper limit of normal (ULN) for age.
* SGPT (ALT) less than or equal to 5x ULN
* Serum albumin greater than or equal to 2 gm/dL

- Adequate renal function:
* Creatinine clearance or glomerular filtration rate >70 ml/min/1.73 m2 or a serum creatinine based on age and gender as follows:

Age Maximum serum creatinine concentration (mg/dL) Male Female 1-