Study of tuvusertib combined with niraparib or lartesertib for patients with ovarian cancer that worsened after previous PARP inhibitor treatment

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What is this study about?

This study is looking at epithelial ovarian cancer that has gotten worse after previous treatment with a type of medicine called a PARP inhibitor. The cancer may also involve the fallopian tubes or the lining of the abdomen, which is called the peritoneum. People in this study will have cancer that carries certain changes in genes called BRCA1 or BRCA2 mutations, or their cancer will have a condition called homologous recombination deficiency, which means the cancer cells have problems repairing their own genetic material. The study will test different combinations of medicines to see which works best. The medicines being used are tuvusertib, which is also called M1774 or MSC2584415A, niraparib, which is sold as Zejula, and lartesertib, which is also called M4076 or MSC2585823A. All of these medicines are taken by mouth as tablets or capsules.

The purpose of this study is to see how well these medicine combinations work at shrinking or stopping the growth of the cancer, and to check how safe they are for people to take. The study will also look at which dose levels work best when the medicines are used together compared to using tuvusertib alone. The study is divided into two parts. In the first part, called Part A, people will receive either tuvusertib combined with niraparib or tuvusertib combined with lartesertib. The results from Part A will help decide which combination works better and should be studied further. In the second part, called Part B, people will receive the best combination chosen from Part A at two different dose levels, or they will receive tuvusertib by itself. This will help compare how well the combination works compared to tuvusertib alone and will help determine the best dose to use in future treatments.

During the study, people will take their assigned medicines and will have regular check-ups to see how the cancer is responding to treatment and to watch for any side effects. These check-ups will include scans to measure the size of the cancer and blood tests to check overall health. The treatment can continue for up to 42 months as long as the cancer does not get worse and the medicine is not causing serious problems. The study will measure how many people have their cancer shrink, how long the cancer stays under control, how long people live without the cancer getting worse, and how long people live overall. The study will also carefully track any unwanted effects or health problems that occur during treatment.

1 Treatment assignment

Upon entering the study, you will be assigned to one of the treatment groups. The study is divided into two parts: Part A and Part B.

In Part A, you may receive either tuvusertib combined with niraparib, or tuvusertib combined with lartesertib. These are medications taken by mouth.

In Part B, you may receive either the combination treatment selected from Part A at two different dose levels, or tuvusertib alone.

The assignment to a specific treatment group will be done randomly, meaning it will be determined by chance, similar to flipping a coin.

2 Medication administration

All medications in this study are taken by mouth.

Niraparib is available as a 100 mg film-coated tablet under the brand name Zejula.

Tuvusertib and lartesertib are provided as capsules or film-coated tablets.

Your study doctor will provide specific instructions on the exact dosage, how many tablets or capsules to take, and at what times of day.

The duration of treatment will depend on how your body responds to the medication and whether you experience any side effects. Treatment will continue as long as your disease does not progress and the medication remains tolerable.

3 Regular monitoring visits

Throughout the study, you will attend regular visits to the study site for monitoring.

During these visits, the study team will assess your overall health and how you are responding to the treatment.

Your performance status will be evaluated using a scale that measures how the disease affects your daily living abilities. This is called the ECOG performance status.

The study team will perform physical examinations and review any symptoms or side effects you may be experiencing.

4 Disease assessment

Your disease will be regularly assessed using imaging scans to determine if the treatment is working.

These assessments will follow a standard method called RECIST v1.1, which is a set of rules used to measure tumors and determine if they are shrinking, staying the same, or growing.

The study team will look for an objective response, which means a measurable reduction in the size of your tumors.

The frequency of these imaging scans will be determined by your study doctor according to the study schedule.

5 Safety monitoring

Your safety will be closely monitored throughout the study.

Blood samples will be taken regularly to check how your body is functioning and to detect any potential side effects from the medications.

You will be asked to report any new symptoms, health changes, or side effects you experience between visits.

The study team will record and evaluate all adverse events, which are any unwanted or harmful effects that occur during the study, whether or not they are related to the study medication.

6 Treatment continuation or discontinuation

You will continue receiving the study medication as long as your disease does not progress and you do not experience unacceptable side effects.

If imaging scans show that your disease is getting worse, or if side effects become too severe, your study doctor may decide to stop your treatment.

The decision to continue or stop treatment will be made based on regular assessments of your disease status and overall health.

7 End of treatment

When you stop taking the study medication, you will have an end-of-treatment visit.

During this visit, final assessments will be performed, including physical examination, blood tests, and imaging scans if needed.

The study team will document the reason for stopping treatment and assess your overall condition.

8 Follow-up period

After completing treatment, you will enter a follow-up period.

During this time, the study team will continue to monitor your health status and disease progression.

You may be asked to return for follow-up visits or to provide updates on your health by phone or other means.

This follow-up will help the study team collect information about long-term outcomes, including progression-free survival (the length of time you live without your disease getting worse) and overall survival (the length of time you live from the start of treatment).

Who Can Join the Study?

To join this study, you must meet all of the following requirements:

You must have a confirmed diagnosis of high grade serous or high grade endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer that has come back after treatment. High grade means the cancer cells look very different from normal cells and tend to grow faster. Primary peritoneal cancer starts in the lining of the abdomen, and fallopian tube cancer starts in the tubes that connect the ovaries to the uterus.
Your tumor must have specific changes in genes called BRCA1 or BRCA2, or your tumor must test positive for HRD status. HRD stands for homologous recombination deficiency, which means your tumor has difficulty repairing damaged genetic material. These test results must be available from standard tests done at your hospital before you begin screening for this study.
Your cancer must have grown or spread while you were taking a type of medicine called a PARP inhibitor, which is a drug that helps fight cancer by blocking a protein that repairs damaged cells. This growth must have happened during your first or second maintenance treatment with PARP inhibitor, and you can only have received one course of PARP inhibitor maintenance treatment. The growth of your cancer must have been confirmed by imaging scans within 28 days of your last dose of PARP inhibitor.
You must have benefited from the PARP inhibitor treatment for at least 6 months before your cancer started growing again.
If your cancer grew during first maintenance PARP inhibitor treatment, you are allowed to have had one additional course of platinum-based chemotherapy before joining this study. The time between finishing platinum chemotherapy and your cancer growing again must be more than 6 months. If your cancer grew during second maintenance PARP inhibitor treatment, you cannot have received any other cancer treatments after the PARP inhibitor.
You must either be unable to tolerate standard treatment options, have refused standard treatment, or your doctor believes that not having standard treatment at this time would not harm you.
Your cancer must be measurable, meaning it can be seen and measured on imaging scans according to specific guidelines called RECIST version 1.1.
You must have an ECOG performance status of 0 or 1, which is a way doctors measure how well you can carry out daily activities. A score of 0 means you are fully active, and a score of 1 means you have some restrictions but can still do light work. You must also be expected to live at least 6 months.
You must be female, as this study only includes female participants.
You must be an adult or elderly person, as this study includes participants aged 18 years and older.
You must meet other requirements defined in the study protocol.

Who Cannot Join the Study?

You have a type of cancer other than epithelial ovarian cancer, which is a cancer that starts in the cells covering the surface of the ovary
Your ovarian cancer has not been previously treated with a PARP inhibitor, which is a type of targeted cancer medicine that blocks proteins that help repair damaged cells
Your ovarian cancer did not progress or get worse while taking a PARP inhibitor in the past
You are male, as this study only includes female patients
You are under 18 years of age, as this study is for adults only
You are pregnant or breastfeeding
You have severe kidney problems that would prevent your body from processing the study medications safely
You have severe liver problems that would affect how your body breaks down the study medications
You have had a recent heart attack, stroke, or serious heart condition
You have uncontrolled high blood pressure that cannot be managed with medication
You have an active infection that requires treatment
You are taking medications that interfere with the study drugs
You have another active cancer that requires treatment
You have a known allergy to any of the study medications or their ingredients
You have had major surgery within the last few weeks before starting the study
You are unable to swallow pills or have digestive problems that prevent proper absorption of medications
You have brain metastases that are not stable or controlled, meaning the cancer has spread to your brain and is still growing

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

Site Name	City	Country
Institut Gustave Roussy	Villejuif	France
Technische Universitaet Dresden	Dresden	Germany
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy
Universitaet Leipzig	Leipzig	Germany
Katholieke Universiteit te Leuven	Leuven	Belgium
Hospital Universitario De Navarra	Pamplona	Spain
IRCCS Humanitas Research Hospital	Rozzano	Italy
Comite Entreprise Paul Papin	Angers	France

Other Sites

Site Name	City	Country
Istituto Oncologico Veneto	Padua	Italy
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy	Bydgoszcz	Poland
Istituto Europeo Di Oncologia S.r.l.	Milan	Italy
IRCCS Istituto Nazionale Tumori Fondazione Pascale	Naples	Italy
Centre hospitalier universitaire de Liege	Liege	Belgium
Universitaetsklinikum Schleswig-Holstein AöR	Kiel	Germany
Hospital Universitario 12 De Octubre	Madrid	Spain
Europejskie Centrum Zdrowia Otwock Sp. z o.o.	Otwock	Poland
Instytut Msf Sp. z o.o.	Lodz	Poland
Institut De Cancerologie Strasbourg Europe	STRASBOURG, Alsace	France
Jagiellońskie Centrum Innowacji Sp. z o.o.	Cracow	Poland
Universitaetsklinikum Regensburg AöR	Regensburg	Germany
Hospital Clinic De Barcelona	Barcelona	Spain
Charite Universitaetsmedizin Berlin KöR	Berlin	Germany
Catharina Ziekenhuis Stichting	Eindhoven	The Netherlands
Aalborg University Hospital	Aalborg	Denmark
Rheinische Friedrich-Wilhelms-Universitaet Bonn	Bonn	Germany
Hospital Universitari De Girona Doctor Josep Trueta	Girona	Spain
Groupe Hospitalier Diaconesses Croix Saint Simon	Paris	France
Rigshospitalet	Copenhagen	Denmark
Centre Hospitalier Lyon Sud	Pierre Benite	France
Hopital Beaujon	Clichy	France
Clinique Victor Hugo	Le Mans	France
Region Sjaelland	Holbæk	Denmark
Centre Francois Baclesse	Caen	France
Cklrqpqrc Uzlwwupmglqwcf Sceyfgnwq	Woluwe-Saint-Lambert	Belgium
Cshthm Lmgm Bpesmd	Lyon	France
Innhxx Ikgholuy Fndcrgubaxdaz Onfjvjhgotk	Rome	Italy
Ionbbuls Ciwysx Dtgmrbkiclrudzuca	L'hospitalet De Llobregat	Spain
Wfqeqirchaj Wuqlvxhifphzcqjnewgr Cgckzpi Oidgcgyfv I Tkmcbmgniopqj Ii Mismwandhto W Lrhda	Lodz	Poland
Scpihifq Pofscnxvf Syu z ogju	Gdynia	Poland
Mlsvordsu Ikextwuajw Cmdkfzxu Sunyzrbu Sxq z ohjc	Warsaw	Poland
Cptpwf dy Rbbihcyyctzbo &eavchi Cpoxiffq Skearj Awim	STRASBOURG, Alsace	France
Aqxmftx Oqutxdbeweh Psb Lnbqivjtadwgvucih Chhiisjtis	Catania	Italy
Uuyzxrowbtngspzhiyabp Msbqlllz Any	Munster	Germany
Nlqsjprf Izoqbvgm Ohwrirmym Imh Mscbv Sqbhhwmfycjefgcwjuzoejivpwqn Icxtdyvq Btmclcvt	Cracow	Poland
Gzlsoz Hbcijqumicl Uvdmgpmronxfd Pmkaj Pozekuwcljs Eg Nmhmrspwrquy	Paris	France
Kzpjvfpa Evkszpqufcsqgmysqttjioya Hydzhanlbpkzdiooq	Essen	Germany
Hszklrlp Uvcxroazxhsru Hunipugj Tbsnr y Pzxmcm Iwqphgsi Cyxfrj dwwtmflwudavrpqcm (lfen	Badalona	Spain
Hbkutyig Vgag dcemjrsr	Barcelona	Spain
Crzivs Ojtxg Lnmhuel	Lille	France

Trial status

Country	Status	Recruitment Start
Belgium	Not recruiting	12.12.2024
Denmark	Not recruiting	12.12.2024
France	Not recruiting	12.12.2024
Germany	Not recruiting	12.12.2024
Italy	Not recruiting	12.12.2024
Poland	Not recruiting	12.12.2024
Spain	Not recruiting	12.12.2024
The Netherlands	Not recruiting	12.12.2024

Trial locations

Investigated drugs:

Tuvusertib is an ATR inhibitor being tested in this study. ATR inhibitors are medications that work by blocking a protein called ATR, which helps cancer cells repair their damaged DNA. By blocking this protein, the medication may help stop cancer cells from growing and surviving.

Niraparib is a PARP inhibitor being tested in combination with tuvusertib. PARP inhibitors work by blocking an enzyme called PARP that helps repair damaged DNA in cells. When this enzyme is blocked, cancer cells with certain genetic mutations may have difficulty repairing themselves and may die.

Lartesertib is an ATM inhibitor being tested in combination with tuvusertib. ATM inhibitors work by blocking a protein called ATM that plays an important role in helping cells respond to DNA damage. Blocking this protein may prevent cancer cells from repairing themselves and may help slow or stop their growth.

Investigated diseases:

Ovarian cancer

Epithelial Ovarian Cancer – Epithelial ovarian cancer is a type of cancer that begins in the thin layer of tissue covering the ovaries, which are the female reproductive organs that produce eggs. This cancer develops when cells in the epithelial tissue start to grow abnormally and uncontrollably, forming tumors. The disease often progresses silently in its early stages, which means symptoms may not appear until the cancer has spread beyond the ovaries. As the cancer advances, it can spread to other parts of the pelvis and abdomen, affecting nearby organs and tissues. The cancer may continue to grow despite initial treatment, and in some cases, it can develop resistance to certain therapies over time. When the disease progresses after previous treatment with specific medications called PARP inhibitors, it means the cancer has continued to grow or spread despite this type of therapy.

Trial ID:

2024-511202-23-00

Protocol code:

MS201924_0002

Trial Phase:

Therapeutic exploratory (Phase II)

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Study of tuvusertib combined with niraparib or lartesertib for patients with ovarian cancer that worsened after previous PARP inhibitor treatment

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?