Phase 3 Randomized Study of Niraparib Tosilate Monohydrate vs. Temozolomide in Newly Diagnosed MGMT Unmethylated Glioblastoma

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What is this study about?

This clinical trial is focused on studying a type of brain cancer called glioblastoma, specifically in cases where a certain gene, known as MGMT, is not altered. The study will compare two treatments: niraparib, a medication taken as a tablet, and temozolomide, which is taken as a capsule. Both medications are designed to be taken orally, meaning they are swallowed.

The purpose of the study is to determine if niraparib can help patients live longer without the disease getting worse, compared to temozolomide. Participants in the study will be randomly assigned to receive either niraparib or temozolomide. The study will monitor the participants over time to see how the treatments affect their health and the progression of their glioblastoma.

Throughout the study, researchers will also look at how the treatments impact overall survival, which means the length of time patients live after starting the treatment. Additionally, the study will assess the participants’ symptoms, quality of life, and any side effects they may experience. This information will help determine the safety and effectiveness of niraparib compared to temozolomide for treating this specific type of glioblastoma.

1 study entry and assignment to treatment

After you join the study, you are assigned to one of 2 treatment groups in a randomized way. Randomized means the treatment is chosen by chance.

The study is open-label, which means you and the study team know which treatment you receive.

2 treatment with niraparib

If you are assigned to niraparib, you take Zejula 100 mg film-coated tablets by mouth.

The dose is 200 mg/m2 once daily. This means the dose is based on your body size and is taken 1 time each day.

The tablets contain niraparib tosilate monohydrate.

Treatment continues for the study period unless it is stopped earlier because of the study rules or because of side effects.

3 treatment with temozolomide

If you are assigned to temozolomide, you take it by mouth.

The dose is 200 mg/m2. This means the dose is based on your body size.

The medicine is taken during the study period according to the study plan, unless it is stopped earlier because of the study rules or because of side effects.

4 study assessments during treatment

During the study, your condition is checked at the time points listed in the study plan.

The study measures whether the cancer gets smaller or disappears. Complete response means no sign of cancer is seen. Partial response means the cancer has shrunk.

Your symptoms, daily function, and health-related quality of life are checked. Health-related quality of life means how the illness and treatment affect your daily life and well-being.

Your thinking and memory are checked with tests called Hopkins Verbal Learning Test, Controlled Oral Word Association, and Trail Making Test Parts A and B.

Your side effects are monitored, including side effects that lead to treatment stopping, treatment breaks, or dose changes.

Your karnofsky performance status is checked. This is a score that shows how well you are able to carry out daily activities.

Your blood tests and other laboratory results are checked, and your vital signs are measured. Vital signs are basic body measurements such as heart rate, blood pressure, and temperature.

The study also checks the frequency and severity of symptoms that you report yourself using PRO-CTCAE. This is a patient-reported questionnaire about treatment side effects.

5 follow-up for study outcomes

The study measures overall survival, which is the time from the date you are assigned to a treatment group until the date of death from any cause.

The study also measures progression-free survival, which is the time from the date you are assigned to a treatment group until the first sign that the disease gets worse or death from any cause, whichever happens first.

Who Can Join the Study?

Have a newly diagnosed glioblastoma in the brain, confirmed by a tissue sample reviewed by the local pathology team.
Have a tumor with an unmethylated MGMT promoter, meaning the MGMT gene control area does not have a chemical change called methylation, as shown by a validated local test.
Be able to start the standard radiation treatment planned for this study, which uses 60 Gy in 30 fractions (60 units of radiation given in 30 smaller treatments), based on the study doctor’s judgment.
Have had no previous treatment for glioblastoma other than surgery to remove the tumor or a biopsy, which is a small tissue sample taken for testing.
Have a Karnofsky performance status of at least 70, which means the person is able to care for themselves and carry out most daily activities.
Have adequate organ function, meaning the major organs such as the liver, kidneys, and bone marrow are working well enough for study treatment.
Have normal blood pressure, or high blood pressure that is well controlled with treatment, with systolic blood pressure no higher than 140 mmHg and diastolic blood pressure no higher than 90 mmHg.
Be taking dexamethasone at a stable dose or a lower dose within 7 days before randomization, and the dose must not be more than 5 mg per day of the equivalent steroid dose. If another corticosteroid is used, the dose must also stay within the allowed equivalent amount. A corticosteroid is a medicine that reduces swelling and inflammation.
Be able to swallow oral medicines whole.
Be at least 18 years old when signing the informed consent form.
Have enough tumor tissue available for later central review and genetic testing, unless the study team approves a smaller amount of tissue on a case-by-case basis.
Have a tumor that was tested locally with an approved method and found to have an MGMT unmethylated promoter result that meets the study’s required cutoff.
Be considered suitable by the study doctor for the planned radiation therapy schedule.
For females: not be pregnant, not planning pregnancy, and not breastfeeding; and either be unable to become pregnant or use a highly effective birth control method with a failure rate of less than 1% per year from screening until at least 180 days after the last study dose.
For females: understand that breastfeeding is not allowed during the study and for 1 month after the last study dose.
For males: agree not to donate sperm during the study treatment period and for at least 6 months after the last dose.
For males: either not have heterosexual activity or use a male condom, and their female partner should use a highly effective birth control method with a failure rate of less than 1% per year.
Be able to sign the informed consent form, which means understanding the study rules and agreeing to follow them.

Who Cannot Join the Study?

Metastatic disease, meaning the cancer has spread to other parts of the body, or predominant leptomeningeal disease, meaning the main spread is to the thin layers around the brain and spinal cord.
Any psychological, family, social, or travel-related problem that could make it hard to follow the study plan or attend follow-up visits.
Unable to have a brain MRI with IV contrast (a brain scan using a dye given into a vein).
If the biopsy or surgery to remove the tumor happened more than 6 weeks before the planned start of radiation treatment.
A surgical wound complication that has not healed well enough at the time of enrollment.
Known allergy or hypersensitivity to niraparib, temozolomide (TMZ), or any ingredient used to make these medicines.
Known allergy or hypersensitivity to dacarbazine (DTIC), a cancer medicine.
Previous treatment with a PARP inhibitor, which is a type of cancer medicine used for some systemic cancers.
Received a live vaccine within 30 days before the planned start of the study treatment. Live vaccines contain weakened germs. Non-live COVID-19 vaccines are allowed.
Received a blood transfusion or colony-stimulating factors within 4 weeks before the planned start of study treatment. Colony-stimulating factors are medicines that help the body make blood cells.
Treatment with another experimental drug or another study treatment within 5 half-lives of that treatment. A half-life is the time it takes for half of a medicine to leave the body.
Current active pneumonitis (lung inflammation) or any past pneumonitis that needed steroids or other medicines that calm the immune system within 90 days before the study starts.
Use of tumor treating fields such as Optune for glioblastoma.
Known IDH mutation (a change in a gene called isocitrate dehydrogenase).
Known H3 mutation (a change in a gene called H3).
Previous diagnosis of WHO grade 2 or 3 glioma, which means a lower-grade brain tumor in the past.
At increased risk of bleeding because of another condition, such as a major injury or major surgery within the past 28 days, except for surgery to remove the tumor.
Any serious gastrointestinal problem, meaning a problem with the stomach or intestines, that could affect how the body absorbs medicine, such as malabsorption or major removal of the stomach or bowel.
Cirrhosis or unstable liver or bile duct disease, including signs such as fluid in the belly, confusion from liver disease, blood clotting problems, low blood protein, enlarged veins in the food pipe or stomach, or ongoing yellowing of the skin or eyes. Stable long-term liver disease may be allowed in some cases.
Known HIV infection unless all of these are true: CD4 count is at least 350/µL, viral load is below 400 copies/mL, there has been no AIDS-defining infection in the past 12 months, there has been no HIV-related cancer in the past 5 years, and HIV treatment has been stable for more than 4 weeks before enrollment.
MDS or AML, or signs that suggest these conditions are present. MDS means myelodysplastic syndrome, a bone marrow disorder, and AML means acute myeloid leukemia, a type of blood cancer.
Another cancer within the past 2 years before registration, except for certain skin cancers, very early bladder cancer, or other cancers that were fully treated and have been free of disease for at least 2 years.
Past history of PRES, which stands for posterior reversible encephalopathy syndrome, a serious brain condition.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
IRCCS Humanitas Research Hospital	Rozzano	Italy
Comite Entreprise Paul Papin	Angers	France
Hospital Universitario De Salamanca	Salamanca	Spain
Universitaetsklinikum Heidelberg AöR	Heidelberg	Germany
University Hospital Maastricht	Maastricht	The Netherlands
Azienda Ospedaliero Universitaria Careggi	Florence	Italy
Centr Georges Francois Leclerc	Dijon	France
Oslo Universitetssykehus HF	Oslo	Norway
Hospital Universitario Hm Sanchinarro	Madrid	Spain
Hospital Universitario De Navarra	Pamplona	Spain

Other Sites

Site Name	City	Country
Istituto Oncologico Veneto	Padua	Italy
Beaumont Hospital	Dublin	Ireland
Centre De Lutte Contre Le Cancer Eugene Marquis	Rennes	France
Virgen del Rocío University Hospital	Sevilla	Spain
Odense University Hospital	Odense	Denmark
Universitaetsklinikum Regensburg AöR	Regensburg	Germany
Universitaetsklinikum Tuebingen AöR	Tuebingen	Germany
Universitair Medisch Centrum Utrecht	Utrecht	The Netherlands
Hospital Clinic De Barcelona	Barcelona	Spain
Charite Universitaetsmedizin Berlin KöR	Berlin	Germany
Klinikum Chemnitz gGmbH	Chemnitz	Germany
Aalborg University Hospital	Aalborg	Denmark
Rheinische Friedrich-Wilhelms-Universitaet Bonn	Bonn	Germany
Centre Hospitalier Universitaire De Nice	Nice	France
Region Midtjylland	Aarhus	Denmark
Centre Hospitalier Universitaire Amiens Picardie	Amiens	France
Rigshospitalet	Copenhagen	Denmark
Netherlands Cancer Institute	Amsterdam	The Netherlands
Instituto Di Ricovero E Cura A Carattere Scientifico	Bologna	Italy
Vivantes Netzwerk fuer Gesundheit GmbH	Berlin	Germany
Centre Hospitalier Lyon Sud	Pierre Benite	France
Hopital Beaujon	Clichy	France
Hospital Universitario 12 De Octubre	Madrid	Spain
Hospital Del Mar	Barcelona	Spain
St. Olavs Hospital HF	Trondheim	Norway
Azienda Sanitaria Locale Napoli 1 Centro	Naples	Italy
Fondazione I.R.C.C.S. Istituto Neurologico Besta	Milan	Italy
Universitaetsklinikum Leipzig AöR	Leipzig	Germany
Iehtdgrd Rddsgxaa Dq Cimadm Df Mafrbgmtzjq	Montpellier	France
Vaajl Uetikjpquoxx	Amsterdam	The Netherlands
Hupedimc Vecq dsounqtm	Barcelona	Spain
Aubkdvidry Pchuktek Hblcaoyh Dk Msswzkfqm	Marseille	France
Apxcmlt Osraxjdojxv Upyugtoqqzonj Curxyaveiyog Dvbnr Seyuiw E Dtlso Sdfznpv Db Twyhow	Turin	Italy
Garcuv Udnncvitpn Fctkniivq	Frankfurt	Germany
Chwwlx Lqog Bphtrd	Lyon	France
Uehtumczji Ddohs Smsbo Dz Rkms Lw Shztrkjb	Rome	Italy
Lzuze Uyaybjjgrzdh Mchnptp Cigwwrl (rkkja	Leiden	The Netherlands
Czli Uhfyyqagva Hvwnccda	Cork	Ireland
Izgianrn Cjlhqq Dimmqzkunbqcujejx	L'hospitalet De Llobregat	Spain

Trial status

Country	Status	Recruitment Start
Denmark	Not yet recruiting	04.12.2024
France	Not recruiting	04.12.2024
Germany	Not recruiting	04.12.2024
Ireland	Not yet recruiting	04.12.2024
Italy	Not recruiting	04.12.2024
Norway	Not recruiting	04.12.2024
Spain	Not recruiting	04.12.2024
The Netherlands	Not recruiting	04.12.2024

Trial locations

Investigated drugs:

Niraparib is the study drug being tested in this trial. It is taken by mouth as a tablet and is being compared with another treatment to see if it can help people with newly diagnosed glioblastoma live longer. The trial is also looking at how safe it is and how well people tolerate it.

Temozolomide is the comparison treatment in this trial. It is also taken by mouth and is a standard cancer medicine used in glioblastoma. It is used here to see how niraparib performs against a treatment already used for this type of brain cancer.

Investigated diseases:

Glioblastoma

MGMT-unmethylated glioblastoma – A fast-growing type of brain tumor that starts in the glial cells, which support nerve cells in the brain. It usually begins as a newly formed mass and then spreads quickly within the brain tissue. As it grows, it can invade nearby areas and cause worsening brain function, headaches, seizures, weakness, or changes in thinking and speech. The term MGMT-unmethylated means the tumor has a specific molecular feature that is associated with this disease type.

Trial ID:

2024-513077-48-00

Protocol code:

IVY-P3-24-021

NCT ID:

NCT06388733

Trial Phase:

Therapeutic confirmatory (Phase III)

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Phase 3 Randomized Study of Niraparib Tosilate Monohydrate vs. Temozolomide in Newly Diagnosed MGMT Unmethylated Glioblastoma

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?