A Phase I Study of Vorinostat in Combination With Vincristine, Irinotecan, and Temozolomide in Children, Adolescents, and Young Adults With Relapsed or Refractory Solid Tumors and CNS Malignancies
概览
- 阶段
- 1 期
- 干预措施
- Vorinostat
- 疾病 / 适应症
- Ewing Sarcoma
- 发起方
- New York Medical College
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- To determine a maximally tolerated (or optimal) dose of vorinostat
- 状态
- 招募中
- 最后更新
- 17天前
概览
简要总结
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.
详细描述
This first cycle will be used to determine whether the patient can tolerate the chemotherapeutic backbone without developing a DLT. The baseline disease evaluation will be obtained following hematologic recovery from the first cycle of chemotherapy, after which combination therapy with vorinostat will be given in subsequent cycles (2-12) w/ modifications if needed. Vorinostat dose escalation in subsequent patient cohorts will occur based on DLT to determine a MTD.
研究者
入排标准
入选标准
- •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
- •Children under 16 years of age must have a Lansky score greater than or equal to
- •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.
排除标准
- •Pregnancy or breast feeding: Women who are pregnant or breast feeding will not be entered on the protocol due to the risks of fetal and teratogenic adverse events with the therapeutic agents used in the protocol therapy.
- •Corticosteroid use: Patients with CNS tumors who have not been on a stable or decreasing dose of corticosteroids for the 7 days prior to the initiation of protocol therapy.
- •Antineoplastic therapy: Patients receiving any other antineoplastic therapy.
- •Medication allergy:
- •Allergy or intolerance to any of the protocol agents: vincristine, irinotecan, temozolomide, or vorinostat.
- •Allergy or intolerance to cephalosporins.
- •Infection: Patients who have any uncontrolled infection, positive blood culture within 48 hours prior to protocol entry, or diagnosed or receiving therapy for Clostridium difficile infection.
- •Patients may not have taken valproic acid or any other histone deacetylase inhibitor for at least 2 weeks prior to study enrollment.
- •Children with neurofibromastosis Type 1, if being used for treatment of a low grade glioma.
研究组 & 干预措施
Vorinostat
The first cycle of chemotherapy will not include the experimental agent vorinostat. This first cycle will be used to determine whether the patient can tolerate the chemotherapeutic backbone without developing a DLT. Cycle 1 * Vincristine: 1.5 mg/m2/day (maximum dose 2 mg) IV Days 1 and 8 over 1-15 minutes. * Temozolomide: 125 mg/m2/day PO Days 1-5. * Irinotecan: 50 mg/m2/day IV Days 1-5 over 60 minutes. * Cefixime: 8 mg/kg/day (maximum dose 400 mg) PO. Begin 2 days prior to irinotecan therapy and continue through Day 8. Cycles 2-12 * Vincristine: 1.5 mg/m2/day (maximum dose 2 mg) IV Days 1 and 8 over 1-15 minutes. * Temozolomide: 125 mg/m2/day PO Days 1-5. * Irinotecan: 50 mg/m2/day IV Days 1-5 over 60 minutes. * Cefixime: 8 mg/kg/day (maximum dose 400 mg) PO. Begin 2 days prior to irinotecan therapy and continue through Day 8. * Vorinostat: Dose per escalation schema daily Days 1-5. * Vorinostat will not be administered during Cycle 1.
干预措施: Vorinostat
结局指标
主要结局
To determine a maximally tolerated (or optimal) dose of vorinostat
时间窗: 1 year
A minimum of 3 evaluable patients will be entered at each dose level. If no significant dose limiting toxicity is discovered, a maximum of 3 dose levels will be evaluated. The minimum patient enrollment will be 3 patients. Many of the patients enrolled on this trial are expected to be heavily pretreated. All patients will be given a VIT only "window" to evaluate adequate bone marrow reserve to tolerate protocol therapy. We expect that at most 20% of patients will not be able to tolerate VIT or VIT with dose reduced temozolomide. A maximum of 24 patients enrolled on study is anticipated. Once the MTD has been defined, up to 6 additional patients may be enrolled to acquire additional safety data regarding this combination of agents.
次要结局
- Overall response rate (ORR) after therapy(1 year)