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Monoclonal Antibodies

Pembrolizumab + Temozolomide + TTFields for Glioblastoma (2-THE-TOP Trial)

Phase 2

Waitlist Available

Led By David Tran, MD, PhD

Research Sponsored by University of Florida

Eligibility Criteria Checklist

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

Must have

Steroid dose equivalent to dexamethasone dose of ≤ 4mg daily at the time of starting adjuvant treatment

Patients must be at least 18 years of age

Must not have

Prior treatment with specific antibodies or drugs targeting T-cell co-stimulation or checkpoint pathways

Prior treatment with anti-angiogenic agents including bevacizumab

Timeline

Screening 3 weeks

Treatment Varies

Follow Up assessed up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing whether adding pembrolizumab to the standard treatment for glioblastoma (surgery, radiation, and chemotherapy) can help patients live longer without their disease progressing.

Who is the study for?

Adults with newly diagnosed Glioblastoma who've had surgery and radiotherapy can join. They must be healthy enough for further treatment, have a life expectancy of at least 3 months, and use effective contraception. Those with certain other cancers, previous treatments like anti-PD-1 or bevacizumab, implanted electronic brain devices, severe allergies to trial drugs, uncontrolled illnesses or active infections cannot participate.

What is being tested?

The study tests if adding Pembrolizumab (an immunotherapy drug) to Temozolomide chemotherapy and TTFields (Optune®), an electric field therapy, extends the time patients live without their brain cancer getting worse compared to past data.

What are the potential side effects?

Possible side effects include immune system reactions that may affect organs; skin reactions from Optune device; fatigue; nausea from Temozolomide; increased risk of infection due to Pembrolizumab's effect on the immune system.

Eligibility Criteria

Inclusion Criteria

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

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I am taking a low dose of steroids, not more than 4mg of dexamethasone daily.

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I am 18 years old or older.

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I am eligible for high dose temozolomide and Optune therapy after my main treatment.

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I am able to care for myself but may not be able to do active work.

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My blood tests show my organs and bone marrow are working well.

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I've had the safest possible surgery and specific treatment for my brain tumor.

Exclusion Criteria

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

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I have been treated with drugs that target the immune system.

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I have previously been treated with medications that stop the formation of new blood vessels.

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I have been diagnosed with HIV.

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I have an active hepatitis B or C infection.

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I have not taken immunosuppressive drugs in the last 7 days.

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I have an active tuberculosis infection.

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I am taking more than 4 mg of steroids daily.

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My cancer has spread to the lining of my brain and spinal cord.

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I have had pneumonitis treated with steroids or have it now.

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I have multiple brain tumors that are separate from each other.

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My tumor is located in the lower part of my brain.

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I have had another type of cancer.

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I have a specific device implanted in my brain or a related condition.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ assessed up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~assessed up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and assessed 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

Progression-free Survival Between the Groups From Time of Enrollment

Secondary study objectives

Augmentation of TTFields-initiated Glioma-specific Immune Reaction by Pembrolizumab

Number of Participants With Toxicities, Serious Adverse Events and/or Other Adverse Events Treated With Triple Combination Treatment

Overall Survival (OS)

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Clostridium difficile colitis

Systemic infection

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Placebo + CRT Followed by Placebo

Pembrolizumab + CRT Followed by Pembrolizumab

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Optune System combined with Temozolomide (TMZ) + PembrolizumabExperimental Treatment3 Interventions

Patients with newly-diagnosed GBM who undergo maximal safe resection (biopsy alone is eligible) followed by chemoradiation consisting of concomitant TMZ daily and radiation therapy (RT) with minimal RT will be eligible for this trial. Four to six weeks after finishing chemoradiation, patients will start monthly cycles of adjuvant TMZ. Treatment with Optune will start at approximately the same time as the first cycle of adjuvant TMZ and continue until second disease progression or a maximum of 2 years. Within one week after starting Cycle 2 of adjuvant TMZ and Optune therapy, patients will begin open-label treatment with pembrolizumab every 3 weeks until first disease progression or unacceptable toxicities or 2 years, whichever comes first.

Group II: Historical ControlExperimental Treatment2 Interventions

Historical control of patients treated with Optune System combined with Temozolomide alone from the EF-14 study will be compared with the Optune System combined with Temozolomide (TMZ) + pembrolizumab

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

Temozolomide (TMZ)

2005

Completed Phase 3

~760