Vorinostat and Temsirolimus With or Without Radiation Therapy in Treating Younger Patients With Newly Diagnosed or Progressive Diffuse Intrinsic Pontine Glioma

NCT02420613 | Completed Phase 1 FDA Drug

• 3 other identifiers: 2014-0135NCI-2015-00817P30CA016672
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of temsirolimus when given together with vorinostat and with or without radiation therapy in treating younger patients with newly diagnosed or progressive diffuse intrinsic pontine glioma, a tumor that arises from the middle portion of the brain stem. Vorinostat and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving temsirolimus and vorinostat with or without radiation therapy may be a better treatment for younger patients with diffuse intrinsic pontine glioma.

Conditions

Diffuse Intrinsic Pontine Glioma

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD) of temsirolimus

  MTD will be defined as the highest dose studied in which six patients have been treated and at most two patients with dose limiting toxicities (DLTs) are observed. DLTs will be monitored for the first course of the combination of vorinostat and temsirolimus.

  28 days (course 1)

• Incidence of toxic death

  Up to 12 months

• Incidence of adverse events

  Adverse events will be tabulated by dose, grade, and attribution.

  Up to 12 months

Secondary Outcomes (1)

• Radiographic response

  Up to 12 months

Study Arms (2)

Arm I (vorinostat, radiation therapy, temsirolimus)

EXPERIMENTAL

CHEMORADIOTHERAPY PHASE: Patients receive vorinostat QD and undergo radiation therapy QD for 30 fractions over 6-7 weeks. MAINTENANCE PHASE: Four to six weeks after the completion of radiation therapy, patients receive vorinostat PO QD and temsirolimus IV over 30-90 minutes on days 1-8 of each cycle. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity.

Radiation: Radiation Therapy; Drug: Temsirolimus; Drug: Vorinostat

Arm II (vorinostat, temsirolimus)

EXPERIMENTAL

Patients receive vorinostat PO QD and temsirolimus IV over 30-90 minutes on days 1-8 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Temsirolimus; Drug: Vorinostat

Interventions

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Arm I (vorinostat, radiation therapy, temsirolimus)

Temsirolimus DRUG

Given IV

Also known as: CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog, Rapamycin Analog CCI-779, Torisel

Arm I (vorinostat, radiation therapy, temsirolimus); Arm II (vorinostat, temsirolimus)

Vorinostat DRUG

Given PO

Also known as: L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza

Arm I (vorinostat, radiation therapy, temsirolimus); Arm II (vorinostat, temsirolimus)

Eligibility Criteria

• Age: 7 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be \> than 6 months and =\< 21 years of age at the time of study consent
• Patients with newly diagnosed or progressive DIPG as confirmed by gadolinium enhanced magnetic resonance imaging (MRI) are eligible; MRI must demonstrate that at least 2/3 of the tumor is situated in the pons and that the origin of the tumor is clearly in the pons; biopsy is not required; tumors with features not typical of diffuse intrinsic brainstem glioma are not eligible; these include dorsally exophytic brainstem gliomas, cervicomedullary junction tumors, and focal low grade gliomas of the midbrain or brainstem which should undergo resection and pathologic evaluation; patients, who have received re-irradiation for progression of the tumor, will be eligible if they show evidence of measurable progressive disease after the re-irradiation; patients at diagnosis with involvement of the spine will not be eligible, however if at progression features of spine involvement are present they will be eligible for stratum II
• Patients must have a Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients=\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy or radiation to grade 2 or less
• Patients must not have received myelosuppressive therapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
• At least 14 days must have passed after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor
• At least 7 days must have elapsed after the last of a biologic agent that is not a monoclonal antibody, to be enrolled on this study
• At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines
• At least 3 half-lives must have elapsed after treatment with a monoclonal antibody and enrollment on this study
• \>= 2 weeks must have elapsed for local palliative radiotherapy (re-irradiation for progressive disease or upfront radiation therapy \[RT\] at initial diagnosis) and enrollment on study for stratum II; at least 24 weeks must have elapsed if patient received craniospinal radiotherapy due to any other prior malignancies
• The patient must have no evidence of active graft vs. host disease, and \>= 12 weeks must have elapsed since transplant or stem cell infusion and enrollment on this study for any other pathology
• Prior treatment with vorinostat is allowed but at least 3 weeks must have elapsed from the last dose and effects of prior therapy have resolved
• Patients with central nervous system (CNS) tumors who are receiving steroids are eligible
• Peripheral absolute neutrophil count (ANC) \>= 1000/uL
• Platelet count \>= 100,000/uL (transfusion independent)

You may not qualify if:

• Patients with other malignancies will not be eligible for stratum I or II; patients with disseminated disease including to the spine will not be eligible for stratum 1 but will be eligible for stratum II
• Patients must not have a history of myocardial infarction, severe or unstable angina, clinically significant peripheral vascular disease, grade 2 or greater heart failure, or serious and inadequately controlled cardiac arrhythmia
• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies
• Patients who are currently receiving enzyme inducing anticonvulsants are not eligible
• Patients who are currently receiving therapeutic anticoagulants (including aspirin, low molecular weight heparin, and others) are not eligible
• Patients who are currently receiving angiotensin-converting enzyme (ACE) inhibitors are not eligible due to the development of angioneurotic edema-type reactions in some subjects who received concurrent treatment with temsirolimus + ACE inhibitors
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial
• Patients with history of allergic reactions attributed to compounds of similar chemical; or biologic composition to vorinostat or temsirolimus are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
• Patients with newly diagnosed DIPG who have received vorinostat previously will not be eligible for stratum I; patients with progressive DIPG will be eligible if they have received either one of the two drugs vorinostat or temsirolimus but will not be eligible for stratum II if have received both the drugs before

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma

Interventions

Radiotherapy; Radiation; temsirolimus; Sirolimus; Vorinostat

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena; Macrolides; Lactones; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Wafik T Zaky

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2015
• First Posted: April 20, 2015
• Study Start: October 5, 2015
• Primary Completion: March 28, 2025
• Study Completion: March 28, 2025
• Last Updated: April 2, 2025

Record last verified: 2025-03

Locations

US (1)