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mTOR Inhibitor

Trametinib + Everolimus for Recurrent Brain Cancer

Phase 1

Recruiting

Led By Sabine Mueller

Research Sponsored by University of California, San Francisco

Eligibility Criteria Checklist

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

Must have

Creatinine clearance or radioisotope growth factor receptor (rGFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows: 1 to < 2 years: 0.6 (male), 0.6 (female); 2 to < 6 years: 0.8 (male), 0.8 (female); 6 to < 10 years: 1 (male), 1 (female); 10 to < 13 years: 1.2 (male), 1.2 (female); 13 to < 16 years: 1.5 (male), 1.4 (female); >= 16 years: 1.7 (male), 1.4 (female)

Participants must have histologically confirmed diagnosis of an LGG (WHO grade I-II) that is recurrent or progressive after prior treatment (biologic, chemotherapy or radiation therapy) or must have a histologically confirmed diagnosis of a high grade glioma (HGG) (WHO grade III-VI)

Must not have

Women of childbearing potential who are pregnant or breast-feeding

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies the side effects and best dose of two drugs, trametinib and everolimus, in treating pediatric and young adult patients with low grade gliomas that has come back (recurrent).

Who is the study for?

This trial is for pediatric and young adult patients with recurrent gliomas, including those with low grade (WHO I-II) or high grade (III-VI) tumors. It's open to participants who've had prior treatments and have stable neurological deficits. They must not be pregnant, agree to use contraception, and meet specific health criteria like adequate blood counts and organ function.

What is being tested?

The trial is testing the combination of two drugs: Trametinib targets a protein called MEK to stop tumor growth, while Everolimus blocks a different pathway that helps tumors grow. The goal is to see if using both drugs together is more effective than using them separately in treating gliomas.

What are the potential side effects?

Potential side effects include skin rash, diarrhea, fatigue, mouth sores, infections due to weakened immune system, liver problems indicated by yellowing of the skin or eyes (jaundice), shortness of breath from lung issues, abnormal blood tests reflecting kidney or pancreas problems.

Eligibility Criteria

Inclusion Criteria

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

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My kidney function is within the required range for my age and gender.

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My brain tumor is low-grade and has returned or worsened after treatment, or it is high-grade.

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My cancer started in the spinal cord or has spread widely.

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I am over 18 and my blood pressure is below 140/90 mm Hg.

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It's been over 6 months since my allogeneic bone marrow transplant or over 3 months since my autologous transplant.

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My cancer can be measured or observed.

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My child's blood pressure is within the normal range for their age, height, and gender.

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I had my last radiation treatment more than 12 weeks ago and my cancer has progressed since then.

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I can provide tissue samples or previous test results for genomic testing.

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I received my last monoclonal antibody treatment over four weeks ago.

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My bilirubin levels are within the normal range for my age.

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I have had treatments other than just surgery for my low-grade glioma.

Exclusion Criteria

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

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I am not pregnant or breastfeeding.

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

Area Under the Curve (AUC) of trametinib and everolimus

Dose limiting toxicities (DLTs) of the combination for both continuous and intermittent dosing schedules

Incidence of adverse events for both continuous and intermittent dosing schedules

+3 more

Side effects data

From 2021 Phase 2 trial • 206 Patients • NCT02034110

47%

Pyrexia

36%

Fatigue

33%

Anaemia

33%

Nausea

33%

Decreased appetite

28%

Rash

22%

Headache

22%

Constipation

22%

Pneumonia

22%

Chills

22%

Dyspnoea

19%

Dizziness

19%

Hypoalbuminaemia

19%

Vomiting

19%

Diarrhoea

19%

Hyponatraemia

17%

Dysphagia

17%

Blood alkaline phosphatase increased

17%

Back pain

14%

Aspartate aminotransferase increased

14%

Hypocalcaemia

14%

Dry mouth

14%

Hyperglycaemia

14%

Arthralgia

14%

Oedema peripheral

14%

White blood cell count decreased

14%

Insomnia

14%

Hypotension

11%

Hypokalaemia

11%

Haemoptysis

11%

Alanine aminotransferase increased

11%

Dry skin

11%

Hypothyroidism

11%

Pruritus

11%

Visual impairment

11%

Weight decreased

11%

Cough

Productive cough

Rash maculo-papular

Upper respiratory tract infection

Mucosal inflammation

Hypercalcaemia

Gastrooesophageal reflux disease

Pleural effusion

Night sweats

Asthenia

Ejection fraction decreased

Electrocardiogram QT prolonged

Gamma-glutamyltransferase increased

Neutrophil count decreased

Neck pain

Rhinorrhoea

Haematochezia

Skin lesion

Acute kidney injury

Seborrhoeic keratosis

Pulmonary embolism

Thrombocytopenia

Atrial fibrillation

Stomatitis

Rhinitis allergic

Tachycardia

Abdominal pain upper

Hyperuricaemia

Leukopenia

Sinusitis

Urinary tract infection

Polyneuropathy

Haematuria

Neutropenia

Ear pain

Abdominal pain

Feeling cold

Non-cardiac chest pain

Pain

Fungal infection

Nasopharyngitis

Blood creatinine increased

Blood urea increased

Neutrophil count increased

Hypomagnesaemia

Myalgia

Neuropathy peripheral

Proteinuria

Nasal congestion

Pneumonitis

Palmar-plantar erythrodysaesthesia syndrome

Pelvic infection

Hypophosphataemia

Sepsis

Tinnitus

Malaise

Cataract

Rhabdomyolysis

Dermatitis acneiform

Erythema nodosum

Femoral neck fracture

Aortic thrombosis

Hyperglycaemic hyperosmolar nonketotic syndrome

Pollakiuria

Flushing

Oesophageal stenosis

Atrioventricular block first degree

Photophobia

Dehydration

Toothache

Oral candidiasis

Urinary retention

Alopecia

Skin mass

Aspiration

Vision blurred

Oedema

Depression

Folliculitis

Staphylococcal infection

Clavicle fracture

Aphasia

Cardiac ventricular thrombosis

Stress cardiomyopathy

Oral pain

Clostridium difficile infection

Diverticulitis

Pneumonia aspiration

Pneumonia necrotising

Wound infection

Hyperkalaemia

Rib fracture

Bladder transitional cell carcinoma

Facial nerve disorder

Hypertension

Paralysis recurrent laryngeal nerve

Syncope

Hallucination

Pulmonary haematoma

Sinus bradycardia

Dry eye

Abdominal distension

Dyspepsia

Gait disturbance

Nodule

Xerosis

Conjunctivitis

Tooth infection

Procedural pain

Blood creatine phosphokinase increased

Platelet count decreased

Weight increased

Flank pain

Muscular weakness

Musculoskeletal chest pain

Pain in extremity

Hypoaesthesia

Paraesthesia

Anxiety

Sleep disorder

Dysphonia

Epistaxis

Upper-airway cough syndrome

Wheezing

Erythema

100%

80%

60%

40%

20%

Study treatment Arm

Anaplastic Thyroid Cancer (ATC) (On-Treatment)

Biliary Tract Cancer (BTC) (On-Treatment)

Gastrointestinal Stromal Tumor (GIST) (On-Treatment)

Low Grade (WHO G1/G2) Glioma (LGG) (On-Treatment)

Anaplastic Thyroid Cancer (ATC) (Post-treatment Survival Follow-up)

Gastrointestinal Stromal Tumor (GIST) (Post-treatment Survival Follow-up)

Low Grade (WHO G1/G2) Glioma (LGG) (Post-treatment Survival Follow-up)

Adenocarcinoma of the Small Intestine (ASI) (Post-treatment Survival Follow-up)

Hairy Cell Leukemia (HCL) (Post-treatment Survival Follow-up)

High Grade (WHO G3/G4) Glioma (HGG) (On-Treatment)

Hairy Cell Leukemia (HCL) (On-Treatment)

Multiple Myeloma (MM) (On-Treatment)

High Grade (WHO G3/G4) Glioma (HGG) (Post-treatment Survival Follow-up)

Adenocarcinoma of the Small Intestine (ASI) (On-Treatment)

Biliary Tract Cancer (BTC) (Post-treatment Survival Follow-up)

Multiple Myeloma (MM) (Post-treatment Survival Follow-up)

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 (trametinib, everolimus)Experimental Treatment2 Interventions

Patients receive dosing per their assigned dose level. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Trametinib

2014

Completed Phase 2

~1630

Everolimus

2010

Completed Phase 4

~1510