Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age1-30
SponsorNew York Medical College
About this trial
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
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
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.
Trial design
Design model
Single group
Treatments tested in this trial
Vorinostat
DrugThis is a phase I study of the combination of four drugs: vorinostat, vincristine, irinotecan, and temozolomide. This is called a Phase I study because the goal is to find the highest dose of vorinostat that investigators can give safely when it is used together with the chemotherapy drugs vincristine, irinotecan and temozolomide. Investigators are using vorinostat because it seems to work against cancer in test tubes and animals. It may be most effective when it is given with chemotherapy. The combination of these three agents together has never been given to children. Vincristine, irinotecan, and temozolomide are approved and used for the treatment of other types of cancer in adults and children. Vorinostat is approved and used to treat cancer in adults. The combination of these four drugs together is experimental. Investigators do not know if this combination of medicines will work in people. There is a lot that investigators do not yet know about this combination of medicines.
Treatment groups
30 Participants
are divided into 1 treatment groupGroup A: VorinostatExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
To determine a maximally tolerated (or optimal) dose of vorinostat
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.
Time frame
1 yearSecondary outcomes
1
Overall response rate (ORR) after therapy
To determine the overall response rate (ORR) of vorinostat in combination with VIT in children, adolescents, and young adults with relapsed or refractory solid tumors. The overall (CR+PR) and best response rates with the 95% confidence intervals will be estimated based on the exact binomial distribution.
Time frame
1 yearSponsors and contacts
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Source ClinicalTrials.gov