What side effects are associated with this type of intervention?

Common treatments for Glioblastoma, such as Vorinostat, Isotretinoin, and Temozolomide, have distinct side effect profiles. Vorinostat can cause fatigue, gastrointestinal issues, and hematologic abnormalities. Isotretinoin is associated with dry skin, mucous membrane dryness, elevated liver enzymes, and hyperlipidemia. Temozolomide often leads to myelosuppression, nausea, vomiting, and fatigue. These side effects are important considerations for patients undergoing treatment.

What prior FDA approvals exist?

Temozolomide, an alkylating agent, is FDA-approved for the treatment of newly diagnosed Glioblastoma in combination with radiotherapy and as maintenance therapy. Vorinostat, a histone deacetylase inhibitor, has been studied in clinical trials for Glioblastoma but is not specifically FDA-approved for this indication. Isotretinoin, a retinoid, has also been investigated in clinical settings for Glioblastoma treatment, though it lacks specific FDA approval for this use. These drugs are part of ongoing research to improve outcomes in Glioblastoma therapy.

What other types of research exist?

Promising novel alternatives for Glioblastoma treatment in 2024 include: <ol> <li>BRAF/MEK inhibitors (e.g., Dabrafenib plus Trametinib) for BRAF V600E-mutant gliomas.</li> <li></li> </ol> PD-1 inhibitors (e.g., Nivolumab) for patients with high PD-L1 expression or mismatch repair deficiency. 3. Bevacizumab, an angiogenesis inhibitor, often combined with other chemotherapies. 4. mTOR inhibitors (e.g., Everolimus) combined with other agents like Octreotide for aggressive meningiomas. 5. NTRK inhibitors for tumors with NTRK fusions. These alternatives are based on recent clinical trials and emerging data.

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Retinoid

Vorinostat + Isotretinoin + Temozolomide for Glioblastoma

Phase 1 & 2

Waitlist Available

Led By Marta Penas-Prado, MD

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients with histologically proven supratentorial WHO grade IV glioma (glioblastoma or gliosarcoma)

Patients must have shown unequivocal evidence for tumor recurrence or progression by MRI scan and should have failed radiation therapy

Must not have

Patients receiving valproic acid will be excluded unless switched to an alternative agent prior to treatment initiation

Patients on previous treatment with carboplatin

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 62 months

Awards & highlights

Approved for 5 Other Conditions

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This study is evaluating whether a drug combination can help control glioblastoma or gliosarcoma.

Who is the study for?

Adults over 18 with recurrent WHO grade IV glioma (glioblastoma or gliosarcoma) who've failed radiation therapy can join. They must be able to sign consent, have a Karnofsky performance status >=60, stable health post-prior treatments, and agree to contraception. Exclusions include other cancers within 3 years (except certain types), prior bevacizumab treatment, valproic acid use without switching drugs first, inability to tolerate study procedures or swallow tablets.

What is being tested?

The trial tests if vorinostat combined with isotretinoin and temozolomide can control recurrent brain tumors in adults and assesses the safety of this drug combination. Participants will undergo surgical resection as needed and receive these medications under careful monitoring for effectiveness and adverse reactions.

What are the potential side effects?

Potential side effects may include blood disorders due to bone marrow suppression; liver function changes; kidney issues; digestive disturbances like nausea or vomiting; fatigue; skin reactions from isotretinoin such as dryness or rash; neurological effects including headaches or seizures.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with a high-grade brain tumor (glioblastoma or gliosarcoma).

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My cancer has grown or returned after radiation, confirmed by an MRI.

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My cancer growth was confirmed not to be due to previous radiation treatments.

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I am willing to follow the iPLEDGE program for isotretinoin treatment.

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I am 18 years old or older.

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I can care for myself but may need occasional help.

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My blood tests for bone marrow, liver, kidneys, and pancreas are normal, and my cholesterol and triglycerides are under control.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not currently taking valproic acid, or I have switched to another medication.

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I have been treated with carboplatin before.

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I am not allergic to vorinostat, temozolomide, or isotretinoin.

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I have never been treated with bevacizumab.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 62 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~62 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 62 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum Tolerated Dose (MTD)

Phase II: To Determine the Efficacy of Vorinostat + cRA, Versus CBT + cRA, Versus Vorinostat + cRA + CBT in Patients With Recurrent Glioblastoma Multiforme as Determined by Time to Progression (TTP) Using an Adaptive Randomization Phase II Trial Design.

Side effects data

From 2011 Phase 3 trial • 661 Patients • NCT00128102

57%

Nausea

47%

Fatigue

43%

Diarrhoea

40%

Vomiting

40%

Decreased appetite

29%

Dyspnoea

24%

Constipation

20%

Weight decreased

18%

Tumour pain

18%

Cough

15%

Pleural mesothelioma malignant advanced

14%

Anaemia

12%

Pyrexia

Insomnia

Dry mouth

Blood creatinine increased

Abdominal pain

Back pain

Dysgeusia

Oedema peripheral

Dizziness

Thrombocytopenia

Headache

C-reactive protein increased

Dehydration

Musculoskeletal pain

Malaise

Pneumonia

Anxiety

Rash

Atrial fibrillation

Accidental overdose

Pleural effusion

Bladder cancer

Overdose

Sepsis

Pneumothorax

Confusional state

General physical health deterioration

Non-cardiac chest pain

Pericarditis

Disseminated intravascular coagulation

Death

Ascites

Dysphagia

Pulmonary embolism

Deep vein thrombosis

100%

80%

60%

40%

20%

Study treatment Arm

Vorinostat

Placebo

Awards & Highlights

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Active Control

Group I: Ph II: Arm 2Experimental Treatment1 Intervention

Surgical Arm

Group II: Ph I: Arm 3Experimental Treatment3 Interventions

Vorinostat plus isotretinoin plus temozolomide

Group III: Ph I: Arm 2Experimental Treatment2 Interventions

Temozolomide plus isotretinoin

Group IV: Ph I: Arm 1Experimental Treatment2 Interventions

Vorinostat plus isotretinoin

Group V: Ph II: Arm 1Active Control1 Intervention

Non-Surgical

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Vorinostat

FDA approved

Isotretinoin

FDA approved

Surgical Resection

2018

Completed Phase 2

~420

Temozolomide

FDA approved

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Vorinostat, a histone deacetylase inhibitor, alters gene expression to inhibit cancer cell survival and proliferation. Isotretinoin, a retinoid, promotes cell differentiation and apoptosis, reducing tumor growth. Temozolomide, an alkylating agent, damages cancer cell DNA, leading to cell death. These mechanisms are vital for Glioblastoma patients as they underscore the need for a multifaceted treatment approach to combat the aggressive nature of the disease, potentially enhancing treatment efficacy and patient outcomes.