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

March 28, 2025 updated by: M.D. Anderson Cancer Center

A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA, Vorinostat) With Temsirolimus in Children With Newly Diagnosed or Progressive Diffuse Intrinsic Pontine Glioma (DIPG)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) or recommended phase 2 dose of temsirolimus in combination with vorinostat given every four weeks in patients with diffuse intrinsic pontine glioma (DIPG).

II. To define and describe the toxicities of the combination vorinostat and temsirolimus administered on this schedule.

SECONDARY OBJECTIVES:

I. To define the antitumor activity of the combination of vorinostat and temsirolimus within the confines of a phase 1 study.

II. To assess the biologic effects of vorinostat and temsirolimus on the signaling pathways of interest in these tumors.

III. To evaluate response with advanced neuroimaging (including magnetic resonance spectroscopy) and correlate with fiber tract changes using tractography and fractional anisotropy.

OUTLINE: This is a dose-escalation study of temsirolimus. Patients are assigned to 1 of 2 arms.

ARM I:

CHEMORADIOTHERAPY PHASE: Patients receive vorinostat once daily (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 intravenously (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.

ARM II: 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.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

7 months to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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)
  • Hemoglobin >= 10.0 gm/dL (transfusion independent)
  • Serum creatinine =< 1.5 x institutional upper limit of normal for age
  • Bilirubin (sum of conjugated + unconjugated) less than 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
  • Serum albumin must be >=2 g/dL
  • Prothrombin time (PT) and international normalized ratio (INR) < 1.2 x ULN
  • Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled
  • Serum cholesterol and serum triglyceride levels must be less than 300 mg/dl
  • Females > 13 years of age or who have achieved menarche must have a negative pregnancy test within 2 weeks of starting treatment (urine or serum) to be eligible and if sexually active must also agree to use contraception; male sexually active patients must agree to use an effective method of contraception
  • Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • Patients must have a life expectancy of >= 2 months; neurologic deficits in patients with CNS tumors must have been relatively stable for a minimum of 1 week prior to starting protocol therapy

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm I (vorinostat, radiation therapy, temsirolimus)

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
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
Drug: Temsirolimus
Given IV
Other Names:
  • Torisel
  • CCI-779
  • CCI-779 Rapamycin Analog
  • Cell Cycle Inhibitor 779
  • Rapamycin Analog
  • Rapamycin Analog CCI-779
Drug: Vorinostat
Given PO
Other Names:
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza
  • L-001079038
  • Suberanilohydroxamic Acid
Experimental: Arm II (vorinostat, temsirolimus)
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
Given IV
Other Names:
  • Torisel
  • CCI-779
  • CCI-779 Rapamycin Analog
  • Cell Cycle Inhibitor 779
  • Rapamycin Analog
  • Rapamycin Analog CCI-779
Drug: Vorinostat
Given PO
Other Names:
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza
  • L-001079038
  • Suberanilohydroxamic Acid

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD) of temsirolimus
Time Frame: 28 days (course 1)
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
Time Frame: Up to 12 months
Up to 12 months
Incidence of adverse events
Time Frame: Up to 12 months
Adverse events will be tabulated by dose, grade, and attribution.
Up to 12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Radiographic response
Time Frame: Up to 12 months
Will be evaluated using the Response Evaluation Criteria in Solid Tumors from the National Cancer Institute. Best response will be tabulated by dose and category (complete response, partial response, stable disease and progressive disease).
Up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
M.D. Anderson Cancer Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Wafik T Zaky, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 5, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 28, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 28, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 15, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 17, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 20, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 2, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 28, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2014-0135 (Other Identifier: M D Anderson Cancer Center)
  • P30CA016672 (U.S. NIH Grant/Contract)
  • NCI-2015-00817 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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