Combining vorinostat with chemotherapy for relapsed solid tumors and CNS cancers

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

This study is testing if adding a drug called vorinostat to chemotherapy can help people with relapsed solid tumors and brain cancers feel better and improve their treatment outcomes.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 1 Year to 30 Years
• Sex: All
• Sponsor: New York Medical College (other)
• Drugs / interventions: chemotherapy, Radiation
• Locations: 1 site (Valhalla, New York)
• Trial ID: NCT04308330 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of vorinostat in combination with chemotherapy agents vincristine, irinotecan, and temozolomide for patients with relapsed or refractory solid tumors and CNS malignancies. The study aims to determine the maximum tolerated dose of vorinostat while monitoring for side effects and evaluating its impact on tumor cells. Patients will undergo a series of treatment cycles, with dose adjustments based on their tolerance and response. The trial focuses on a specific age group, allowing for a targeted approach to treatment.

Who should consider this trial

Good fit: Ideal candidates are patients aged 1 to 30 years with relapsed or refractory solid tumors or CNS malignancies.

Not a fit: Patients who have received certain prior therapies or those with significant health issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could provide a new treatment option for patients with difficult-to-treat tumors.

How similar studies have performed: While this approach is novel in its specific combination, similar studies have shown promise in treating relapsed tumors with multi-agent chemotherapy.

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-\<2 years 0.6 0.6 2-\<6 years 0.8 0.8 6-\<10 years 1 1 10-\<13 years 1.2 1.2 13-\<16 years 1.5 1.4 greater than or equal to 16 years 1.7 1.4 The threshold creatinine values in this table were derived from the Schwartz formula to estimate glomerular filtration rates (Schwartz et al. J. Peds. 106; 522. 1985) using child length and stature data from the CDC.

\- Informed consent: All patients less than 18 years of age must sign a written informed consent. For patients \<18 years of age, a parent or guardian must sign a written informed consent, unless the patient is an emancipated minor. Childhood assent, when appropriate, should be obtained as well per institutional guidelines.

Exclusion Criteria:

* 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.

Where this trial is running

Valhalla, New York

• New York Medical College — Valhalla, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Jeremy Rosenblum, MD — New York Medical College
• Study coordinator: Harshini Mahanti, BS

Conditions: Ewing Sarcoma, Rhabdomyosarcoma, Wilms Tumor, Neuroblastoma, Hepatoblastoma, Germ Cell Tumor