What side effects are associated with this type of intervention?

Common treatments for brain tumors, particularly those involving BTK inhibitors like Ibrutinib and IDO inhibitors like Indoximod, often include chemotherapy agents such as cyclophosphamide and etoposide. Known side effects of these treatments include cardiotoxicity, neurocognitive dysfunction, fatigue, and an increased risk of infections. Chemotherapy agents can also cause neutropenia, thrombocytopenia, and gastrointestinal issues.

What prior FDA approvals exist?

While specific FDA approvals for Ibrutinib (BTK Inhibitor) and Indoximod (IDO Inhibitor) in the treatment of brain tumors are not detailed, other targeted therapies and immunotherapies have shown promise. For instance, dabrafenib and trametinib, which target BRAF V600E mutations, have been evaluated in clinical trials for gliomas. Additionally, temozolomide, an oral alkylating agent, is widely used for treating glioblastoma. These treatments highlight the ongoing efforts to improve outcomes for brain tumor patients through targeted and combination therapies.

What other types of research exist?

Promising novel alternatives for brain tumor patients include GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas, ONC201 (a selective DRD2 antagonist) for recurrent glioblastoma, and the oncolytic DNX-2401 virus for pediatric diffuse intrinsic pontine glioma. Additionally, investigational IDH-targeted approaches such as Ivosidenib and Vorasidenib for IDH-mutant gliomas are also noteworthy.

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Alkylating Agent

Chemo-immunotherapy for Pediatric Brain Cancer

Phase 1

Recruiting

Led By Theodore S. Johnson, MD, PhD

Research Sponsored by Theodore S. Johnson

Eligibility Criteria Checklist

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

Must have

No concurrent anti-neoplastic therapy other than that described by this clinical study protocol (GCC2020) may be administered with the intent to treat the patient's malignancy while they remain enrolled on this study

Adequate renal function: Creatinine clearance (CLcr) > 25 mL/min (by calculated methods) AND Creatinine ≤ 1.5-times upper limit of age-adjusted normal for age of patient

Must not have

Known central nervous system lymphoma

Requires anticoagulation with warfarin or equivalent vitamin K antagonists

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment combining two drugs, ibrutinib and indoximod, with chemotherapy for young patients whose brain cancer has not responded to other treatments. The goal is to boost the immune system's ability to fight the cancer by blocking proteins that help cancer cells survive.

Who is the study for?

This trial is for young people aged 12-25 with relapsed or refractory primary brain cancer, such as glioblastoma or medulloblastoma. They must be able to swallow pills, have no curative treatment options left, and not be pregnant. Participants need proper kidney and liver function, controlled seizures if present, and a certain level of physical ability.

What is being tested?

The study tests the combination of Ibrutinib (BTK-inhibitor) with Indoximod (IDO-inhibitor) alongside chemotherapy drugs Cyclophosphamide and Etoposide in pediatric brain cancer patients. It aims to find the safest dose that enhances immune response against tumors without severe overlapping toxicity.

What are the potential side effects?

Potential side effects include those common to chemotherapy like nausea, fatigue, hair loss; plus specific risks from Ibrutinib such as bleeding problems or heart rhythm issues; and Indoximod may cause immune-related adverse effects.

Eligibility Criteria

Inclusion Criteria

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

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I am not receiving any cancer treatments other than what this study offers.

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My kidney function is within the required range for the trial.

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My brain cancer has worsened or not responded to treatment, and there are no standard cures left for me.

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I can do most activities but need help with some.

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My blood tests show I have enough neutrophils, platelets, and hemoglobin.

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I have been treated with the chemotherapy drugs listed in this study before.

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My current disease was confirmed active by an MRI with contrast.

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My liver tests are within the normal range, or any high bilirubin is due to Gilbert's syndrome.

Exclusion Criteria

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

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I have been diagnosed with lymphoma in my brain or spinal cord.

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I need blood thinners like warfarin.

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I do not have HIV, active Hepatitis B or C, or any uncontrolled infections.

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I am on long-term medication that strongly affects liver enzyme activity.

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I cannot swallow pills.

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I have not had major surgery or unhealed wounds in the last 4 weeks.

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I have not received any live vaccines in the last 4 weeks.

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My heart's electrical system has a specific irregularity.

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I am receiving treatment for an active autoimmune disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Incidence of regimen-limiting toxicity (RLT)

Objective Response Rate (ORR)

Secondary study objectives

Adverse events (AEs)

Complete Response Rate (CRR)

Frequency of cycle delays for toxicity

+5 more

Side effects data

From 2022 Phase 3 trial • 201 Patients • NCT03053440

37%

Diarrhoea

32%

Upper respiratory tract infection

29%

Muscle spasms

28%

Contusion

24%

Arthralgia

24%

Hypertension

22%

Oedema peripheral

22%

Anaemia

21%

Epistaxis

20%

Cough

19%

Rash

19%

Fatigue

18%

Back pain

18%

Atrial fibrillation

17%

Urinary tract infection

16%

Neutropenia

16%

Thrombocytopenia

15%

Nausea

15%

Headache

15%

Vomiting

14%

Pneumonia

14%

Dizziness

13%

Haematuria

12%

Peripheral swelling

12%

Pyrexia

12%

Constipation

11%

Localised infection

10%

Pain in extremity

10%

Onychoclasis

10%

Fall

10%

Oropharyngeal pain

10%

Lower respiratory tract infection

10%

Sinusitis

10%

Palpitations

Insomnia

Nasopharyngitis

Hyperuricaemia

Dyspnoea

Haematoma

Skin laceration

Paraesthesia

Dyspepsia

Dry skin

Cellulitis

Conjunctivitis

Skin infection

Iron deficiency

Anxiety

Rhinitis

Cataract

Conjunctival haemorrhage

Pruritus

Hypokalaemia

Syncope

Vision blurred

Abdominal pain

Abdominal pain upper

Nail infection

Neck pain

Purpura

Asthenia

Abdominal discomfort

Gingival bleeding

Mouth ulceration

Chest pain

Stomatitis

Onychomycosis

Rhinorrhoea

Actinic keratosis

Dermatitis

Petechiae

Influenza like illness

COVID-19

Gastroenteritis

Tooth infection

Limb injury

Squamous cell carcinoma of skin

Peripheral sensory neuropathy

Rosacea

Increased tendency to bruise

Gout

Basal cell carcinoma

Folliculitis

Oral herpes

Gastrooesophageal reflux disease

Retinal haemorrhage

Haemorrhoids

Angina pectoris

Dry mouth

Vertigo

Ecchymosis

Sepsis

Chills

Bronchitis

Furuncle

Joint injury

Blood alkaline phosphatase increased

Neutrophil count decreased

Decreased appetite

Joint swelling

Depression

Productive cough

Skin ulcer

Atrial flutter

Hyperglycaemia

Herpes zoster

Sinus bradycardia

Inguinal hernia

Tinnitus

Dysphagia

Dry eye

Dysuria

Bladder transitional cell carcinoma

Rotator cuff syndrome

Pollakiuria

Abdominal distension

Hypoalbuminaemia

Osteoporosis

Erythema

Acute myocardial infarction

Malaise

Cystitis

Alanine aminotransferase increased

Gamma-glutamyltransferase increased

Musculoskeletal chest pain

Seborrhoeic keratosis

Neuralgia

Benign prostatic hyperplasia

Dyspnoea exertional

Nasal congestion

Pneumonitis

Psoriasis

Skin fissures

Skin lesion

Laryngitis

Respiratory tract infection

Bradycardia

Acute kidney injury

Wound infection

Myalgia

Skin toxicity

Ear infection

Paronychia

Osteoarthritis

Pericarditis

Sciatica

Ocular hyperaemia

Nail disorder

Pleural effusion

Rectal haemorrhage

Cholecystitis

COVID-19 pneumonia

Drug withdrawal syndrome

Seasonal allergy

Vitamin D deficiency

Rash maculo-papular

Hypotension

Death

Loss of consciousness

Post procedural haemorrhage

Laryngeal oedema

Stress fracture

Lumbar vertebral fracture

Haemolytic anaemia

Haemorrhagic disorder

Viral infection

Wound infection staphylococcal

Cardiac failure acute

Wheezing

Colitis

Oral blood blister

Upper gastrointestinal haemorrhage

Drug-induced liver injury

Bacterial sepsis

Brain abscess

Device related infection

Gastrointestinal infection

Neurocryptococcosis

Septic shock

Streptococcal bacteraemia

Femoral neck fracture

Femur fracture

Subdural haematoma

Lethargy

Subarachnoid haemorrhage

Chronic kidney disease

Urinary bladder haemorrhage

Prostatitis

Acute pulmonary oedema

Hyponatraemia

Muscular weakness

Rash erythematous

Hyperviscosity syndrome

Melaena

Clostridium difficile infection

Post procedural sepsis

Pyelonephritis

Cerebrovascular accident

Respiratory disorder

Lymphadenopathy

Streptococcal sepsis

Amyloidosis

Influenza

Pneumonia viral

Coronary artery disease

Pericardial haemorrhage

Urosepsis

Spinal stenosis

100%

80%

60%

40%

20%

Study treatment Arm

Arm A: Ibrutinib

Arm B: Zanubrutinib

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment RegimenExperimental Treatment4 Interventions

Patients will be treated with the 4-drug chemo-immunotherapy regimen. Cycles are a minimum of 28 days.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

2010

Completed Phase 4

~2310

Ibrutinib

2014

Completed Phase 4

~2060

Indoximod

2014

Completed Phase 2

~750

Etoposide

2010

Completed Phase 3

~2960

0 / 17Eligibility 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

Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, and Indoximod, an indoleamine 2,3-dioxygenase (IDO) inhibitor, are being studied for their potential to enhance anti-tumor immune responses in brain tumor patients. Ibrutinib blocks BTK, a key enzyme in the signaling pathways of B cells, which can reduce tumor growth and survival. Indoximod inhibits IDO, an enzyme that suppresses immune responses by degrading tryptophan, thereby enhancing the body's ability to mount an immune response against tumor cells. These mechanisms are crucial for brain tumor patients as they offer a targeted approach to disrupt tumor growth and improve immune system efficacy, potentially leading to better clinical outcomes with manageable toxicity.

RAF and MEK inhibitor therapy in adult patients with brain tumors: a case-based overview and practical management of adverse events.Bioinformatics analysis reveals potential candidate drugs for different subtypes of glioma.