30 Participants Needed

Vorinostat + Chemotherapy for Cancer

(NYMC195 Trial)

HM
LH
Overseen ByLauren Harrison, MSN
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This trial tests a new mix of four medicines to treat tumors that are hard to treat with usual methods. The goal is to find the safest dose and see if this combination can effectively fight these tough tumors.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take any other cancer treatments or certain drugs like valproic acid for at least 2 weeks before joining. If you're on corticosteroids for a CNS tumor, your dose must be stable or decreasing for 7 days before starting the trial.

What data supports the effectiveness of the drug Vorinostat in cancer treatment?

Vorinostat, a drug that affects how genes are turned on and off, is already approved for treating T-cell lymphoma and shows potential in treating breast cancer and acute leukemias. It has also been studied in combination with other drugs for non-small cell lung cancer, suggesting it may help in various cancer types.12345

Is vorinostat safe for use in humans?

Vorinostat has been studied in humans, and common side effects include mild to moderate diarrhea, nausea, fatigue, and loss of appetite. More severe side effects can include significant fatigue, low platelet counts, and severe diarrhea, but no deaths related to the drug were reported in the studies.25678

What makes the drug Vorinostat unique for cancer treatment?

Vorinostat is unique because it is a histone deacetylase inhibitor (HDACi) that can regulate gene expression and induce cancer cell death, and it is being explored for use in combination with chemotherapy for various cancers, including breast cancer and acute leukemias. Its mechanism of action and potential to enhance the effects of other cancer drugs make it a novel option compared to standard treatments.12356

Research Team

JR

Jeremy Rosenblum, MD

Principal Investigator

New York Medical College

Eligibility Criteria

This trial is for young patients (1 to 30 years old) with relapsed or refractory solid tumors or CNS malignancies. They must have adequate organ function, not received certain treatments recently, and cannot be pregnant or breastfeeding. Those with uncontrolled infections, allergies to protocol drugs, or recent use of specific inhibitors are excluded.

Inclusion Criteria

You have enough infection-fighting white blood cells in your body.
It's been over 14 days since my last radiation therapy, or longer for specific types.
Your hemoglobin level is 8 gm/dL or higher.
See 15 more

Exclusion Criteria

I am not allergic to vincristine, irinotecan, temozolomide, or vorinostat.
My child has neurofibromatosis Type 1 and is being treated for a low grade brain tumor.
I haven't taken valproic acid or similar drugs in the last 2 weeks.
See 5 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Chemotherapy Cycle

Participants receive vincristine, temozolomide, irinotecan, and cefixime to assess tolerance without vorinostat

3 weeks
Weekly visits for drug administration

Combination Treatment Cycles

Participants receive combination therapy with vorinostat, vincristine, temozolomide, irinotecan, and cefixime

11 cycles (approximately 33 weeks)
Weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Vorinostat
Trial OverviewThe study tests the highest safe dose of vorinostat combined with vincristine, irinotecan, and temozolomide in children and young adults. It aims to determine side effects, impact on tumor cell molecules, and overall treatment effectiveness against stubborn tumors.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: VorinostatExperimental Treatment1 Intervention
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.

Vorinostat is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Zolinza for:
  • Cutaneous T-cell lymphoma
🇪🇺
Approved in European Union as Zolinza for:
  • Cutaneous T-cell lymphoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

New York Medical College

Lead Sponsor

Trials
73
Recruited
8,700+

Findings from Research

Vorinostat (SAHA) shows varying effectiveness in treating breast cancer, with some tumors and cell lines being resistant due to differences in gene expression related to cell adhesion and glutathione metabolism.
Depleting glutathione with buthionine sulfoximine (BSO) can enhance the effectiveness of SAHA, suggesting that evaluating antioxidant gene expression may help predict which tumors will respond to this treatment.
Redox-Mediated Suberoylanilide Hydroxamic Acid Sensitivity in Breast Cancer.Chiaradonna, F., Barozzi, I., Miccolo, C., et al.[2018]
A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed to accurately measure vorinostat and its metabolites in human serum, with a lower limit of quantitation of 3.0 ng/ml for each analyte.
This assay is currently being utilized in at least 12 clinical studies, highlighting its importance in evaluating the pharmacokinetics and therapeutic effects of vorinostat as an antineoplastic agent.
A liquid chromatography-electrospray ionization tandem mass spectrometric assay for quantitation of the histone deacetylase inhibitor, vorinostat (suberoylanilide hydroxamicacid, SAHA), and its metabolites in human serum.Parise, RA., Holleran, JL., Beumer, JH., et al.[2018]
Vorinostat, when used sequentially before cytosine arabinoside (ara-C), showed mostly synergistic effects in killing leukemia cells, suggesting a promising treatment strategy for acute leukemias.
The combination of vorinostat with etoposide was found to be additive to synergistic, especially when etoposide was administered after vorinostat, indicating that the timing of drug administration is crucial for maximizing therapeutic efficacy.
Preclinical studies of vorinostat (suberoylanilide hydroxamic acid) combined with cytosine arabinoside and etoposide for treatment of acute leukemias.Shiozawa, K., Nakanishi, T., Tan, M., et al.[2018]

References

Redox-Mediated Suberoylanilide Hydroxamic Acid Sensitivity in Breast Cancer. [2018]
A liquid chromatography-electrospray ionization tandem mass spectrometric assay for quantitation of the histone deacetylase inhibitor, vorinostat (suberoylanilide hydroxamicacid, SAHA), and its metabolites in human serum. [2018]
Preclinical studies of vorinostat (suberoylanilide hydroxamic acid) combined with cytosine arabinoside and etoposide for treatment of acute leukemias. [2018]
Phase I/II trial of vorinostat (SAHA) and erlotinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations after erlotinib progression. [2022]
Solubilization of vorinostat by cyclodextrins. [2018]
Assessment of developmental toxicity of vorinostat, a histone deacetylase inhibitor, in Sprague-Dawley rats and Dutch Belted rabbits. [2018]
A study to determine the effects of food and multiple dosing on the pharmacokinetics of vorinostat given orally to patients with advanced cancer. [2018]
Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes. [2021]