This study has been transitioned to CTIS with ID 2023-506551-23-00 check the CTIS register for the current data. This study has two parts. The purpose of the first part of the study is to investigate if the investigational drug called dostarlimab (…
ID
Source
Brief title
Condition
- Uterine, pelvic and broad ligament disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoints for Part 1:
The primary efficacy endpoint of PFS is based on the investigator assessment,
which is defined as the time from the date of randomization to the earliest
date of radiographic assessment of PD or death by any cause in the absence of
PD, whichever occurs first. Tumor response will be evaluated using RECIST v.1.1.
The primary efficacy endpoint of overall survival is defined as the time from
randomization to the date of death by any cause.
Primary Endpoint for Part 2:
The primary efficacy endpoint of PFS is based on the investigator assessment,
which is defined as the time from the date of randomization to the earliest
date of radiographic assessment of PD or death by any cause in the absence of
PD, whichever occurs first. Tumor response will be evaluated using RECIST v.1.1.
Overall Survival (OS) is a primary endpoint for Part 1, and is defined as the
time from randomization to the date of death by any cause.
Secondary outcome
Secondary efficacy endpoints are the following:
• OS, defined as the time from randomization to the date of death by any cause
• PFS based on BICR assessment, defined as the time from randomization to the
earliest date of assessment of PD per RECIST v.1.1 or death by any cause in the
absence of PD per RECIST v.1.1, whichever occurs first
• ORR based on BICR and Investigator assessment, defined as the proportion of
subjects with a best overall response (BOR) of complete response (CR) or
partial response (PR)
• DOR based on BICR and Investigator assessment, defined as the time from the
first documentation of CR or PR until the time of the first documentation of
subsequent PD per RECIST v.1.1 or death by any cause in the absence of PD per
RECIST v.1.1, whichever occurs first
• DCR based on BICR and Investigator assessment, defined as the proportion of
subjects who have achieved a BOR of CR, PR, or stable disease per RECIST v.1.1
• PFS2, defined as the time from treatment randomization to the date of
assessment of progression on the first subsequent anticancer therapy following
study treatment or death by any cause, whichever is earlier
• PRO assessment of treatment using EQ-5D-5L, EORTC QLQ-C30, and EORTC QLQ EN24
• PK and immunogenicity of dostarlimab (Part 1 and Part 2) and PK of niraparib
when administered in combination with dostarlimab (Part 2 only)
Background summary
The use of dostarlimab and niraparib in combination with carboplatin and
paclitaxel in this study are experimental or investigational, meaning that the
four drugs have never been approved to be used together for this purpose.
Dostarlimab is an investigational drug, which means that it has not been
approved by any regulatory authorities, including the United States Food and
Drug Administration (FDA) and European Medicines Agency (EMA). At this time,
dostarlimab cannot be prescribed for this disease (outside of the study).
Niraparib is a targeted therapy that has been approved by the FDA and EMA for
the treatment of certain types of ovarian cancer.
Carboplatin and paclitaxel are types of chemotherapy that have been approved by
the FDA and the EMA for treatment of other cancer types.
Dostarlimab belongs to a class of drugs called PD-1 inhibitors that use the own
immune system to treat cancer (immuno-therapy). It is designed to stop cancer
from growing by helping the immune system recognize and fight the cancer.
Dostarlimab is designed to help the immune system by attaching to a protein
called PD-1 and stopping one of the signals that keeps the immune system from
recognizing the cancer. This may help the immune system attack and destroy the
cancer cells. Other drugs that work in a similar way have already been approved
in some countries and used for the treatment of other cancers.
Study objective
This study has been transitioned to CTIS with ID 2023-506551-23-00 check the CTIS register for the current data.
This study has two parts.
The purpose of the first part of the study is to investigate if the
investigational drug called dostarlimab (also known as TSR-042) in combination
with standard chemotherapy (carboplatin and paclitaxel) will improve the
treatment of endometrial cancer. This part of the study is closed to new
participants.
The second part is to find out if adding a medication called niraparib to
dostarlimab in combination with chemotherapy (carboplatin and paclitaxel), can
help delay worsening of endometrial cancer.
Study design
This is a Phase 3, randomized, double-blind, multicenter study consisting of 2
parts. Part 1 is to evaluate the efficacy and safety of treatment with
dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus
treatment with placebo plus carboplatin-paclitaxel followed by placebo in
subjects with recurrent or primary advanced (Stage III or IV) endometrial
cancer. Part 2 is to evaluate the efficacy and safety of treatment with
dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib
versus treatment with placebo plus carboplatin-paclitaxel followed by placebo
in subjects with recurrent or primary advanced (Stage III or IV) endometrial
cancer. Eligible subjects will be enrolled in Part 1 until enrollment is
complete, then Part 2 will open for enrollment. Part 1 subjects may not enroll
in Part 2. Part 1 and Part 2 will each have an experimental and control arm as
follows:
Part 1: Eligible subjects will be randomized in a 1:1 ratio to the following:
• Arm 1: Subjects will receive dostarlimab intravenous (IV) plus carboplatin
paclitaxel followed by dostarlimab IV .
• Arm 2: Subjects will receive placebo IV plus carboplatin-paclitaxel followed
by placebo IV.
Subjects in Arm 1 and Arm 2 will be stratified by MMR/MSI status as dMMR/MSI-H
or MMRp/MSS, prior external pelvic radiotherapy (yes or no), and disease status
(recurrent, primary Stage III, or primary Stage IV). For local determination of
MMR/MSI status, IHC, next-generation sequencing (NGS), and polymerase chain
reaction (PCR) assays will be accepted. Approximately 470 subjects are planned
for enrollment in Part 1.
Part 2: Eligible subjects will be randomized in a 2:1 ratio to the following:
• Arm 3: Subjects will receive dostarlimab IV plus carboplatin-paclitaxel
followed by dostarlimab IV plus niraparib orally (PO).
• Arm 4: Subjects will receive placebo IV plus carboplatin-paclitaxel followed
by placebo IV and placebo PO.
Subjects in Arm 3 and Arm 4 will be stratified by MMR/MSI status as dMMR/MSI H
or MMRp/MSS, prior external pelvic radiotherapy (yes or no), and disease status
(recurrent, primary Stage III, or primary Stage IV). Approximately 270 subjects
are planned for enrollment in Part 2. The randomization schedules will be
independent for Part 1 and Part 2.
This study consists of a Screening Period (Day -28 to Day -1), a Treatment
Period, an End-of-Treatment (EOT) Visit, a Safety Follow-up Visit, and a
Survival Assessment Period.
During the Treatment Period, study drug administration will occur in 3-week
cycles for the first 6 cycles and in 6-week cycles for all following cycles
starting with Cycle 7.
Part 1:
• Arm 1: Subjects will receive dostarlimab IV in combination with
carboplatin-paclitaxel every 3 weeks (Q3W) for 6 cycles starting at Cycle 1 Day
1 (Study Day 1); followed by dostarlimab IV monotherapy every 6 weeks (Q6W)
starting at Cycle 7 Day 1 for up to 3 years or until progression of disease
(PD), unacceptable toxicity, withdrawal of consent, Investigator*s decision, or
death. Dostarlimab or placebo is to be administered prior to administration of
carboplatin-paclitaxel. It is recommended that paclitaxel be administered
before carboplatin; however, carboplatin may be administered first, if this is
the current local institutional practice.
• Arm 2: Subjects will receive placebo IV in combination with
carboplatin-paclitaxel Q3W for 6 cycles starting at Cycle 1 Day 1 (Study Day 1)
followed by placebo IV Q6W starting at Cycle 7 Day 1 for up to 3 years or until
PD, unacceptable toxicity, withdrawal of consent, Investigator*s decision, or
death.
Part 2:
• Arm 3: Subjects will receive dostarlimab IV in combination with
carboplatin-paclitaxel Q3W for 6 cycles starting at Cycle 1 Day 1 (Study Day
1); followed by dostarlimab IV Q6W in combination with niraparib PO
administered daily (QD) starting at Cycle 7 Day 1, up to 3 years or until PD,
unacceptable toxicity, withdrawal of consent, Investigator*s decision, or death.
• Arm 4: Subjects will receive placebo IV in combination with
carboplatin-paclitaxel Q3W for 6 cycles starting at Cycle 1 Day 1 (Study Day
1); followed by placebo IV Q6W and placebo PO QD starting at Cycle 7 Day 1 for
up to 3 years or until PD, unacceptable toxicity, withdrawal of consent,
Investigator*s decision, or death.
Tumor imaging will be conducted Q6W (±7 days) from the randomization date until
Week 25 (Cycle 8), followed by every 9 weeks (±7 days) until Week 52.
Subsequent tumor imaging will be performed every 12 weeks (±7 days) until
radiographic PD is documented by Investigator assessment per RECIST v1.1
followed by one additional imaging assessment 4-6 weeks later, or subsequent
anticancer therapy is started, whichever occurs first. Thereafter, scans may be
performed per standard of care. If a subject discontinues treatment for a
reason other than PD, death, withdrawal of consent, or loss to follow-up,
radiographic scans are to continue at the specified intervals.
It is required that a follow-up scan is performed a minimum of 4 weeks and up
to 6 weeks after the first PD assessment by Investigator per RECIST v1.1. To
continue study treatment after initial evidence of PD, subjects must be
clinically stable (ie, no signs or symptoms of clinically significant PD,
including worsening of laboratory values, no rapid PD, no decline in Eastern
Cooperative Oncology Group (ECOG) performance status, and no progressive tumor
at critical anatomical sites [eg, cord compression and intracranial tumor
hemorrhage] requiring urgent medical intervention). It is highly recommended
that clinically stable subjects not be discontinued until PD is confirmed.
PRO assessments (EQ-5D-5L, EORTC QLQ-C30, and EORTC-QLQ-EN24) will be collected
at every clinic visit and during every survival follow-up assessment if the
questionnaires are available in the subject*s primary or preferred language.
Blood samples to assess PK and immunogenicity will be collected from all
subjects before and after treatment administration. PK and immunogenicity of
dostarlimab will be analyzed only in subjects administered at least 1 dose of
dostarlimab and PK of niraparib (when administered in combination with
dostarlimab) will be analyzed only in subjects from Part 2 who were
administered at least 1 dose of niraparib. Blood samples for the analysis of
exploratory
biomarkers will be collected at set timepoints during and at the end of
treatment.
Collection and recording of all adverse events (AEs) for each subject will
start on the day of signing the informed consent form. Nonserious AEs will be
collected up until the day of the EOT Visit (see Section 7.1). Serious adverse
events (SAEs) should be reported through 90 days after the last dose of study
treatment or until the subject starts alternate anticancer therapy, whichever
occurs first. Study drug-related SAEs will be collected through 90 days after
the last dose of study treatment. Any pregnancies are to be captured through
180 days posttreatment.
Intervention
Part 1:
Subjects will be randomized in a 1:1 ratio to receive either dostarlimab plus
carboplatin-paclitaxel or placebo plus carboplatin-paclitaxel.
Part 2:
Subjects will be randomized in a 2:1 ratio to receive either dostarlimab plus
carboplatin-paclitaxel followed by dostarlimab IV plus niraparib orally or
placebo plus carboplatin-paclitaxel followed by placebo IV and placebo orally.
Study burden and risks
For Study Drug: DOSTARLIMAB
As of January 2022, dostarlimab has been studied in about 1800 patients with
advanced or recurrent solid tumors in medical research studies, with about 1160
of these patients receiving dostarlimab in combination with other medicines.
Some of the side effects mentioned below can be life-threatening or fatal.
These side effects are considered very common in patients who took dostarlimab
(may affect more than 1 in 10 people):
• Decrease in the number of red blood cells that carry oxygen. Low red blood
cells count may make you feel tired or short of breath and symptoms may require
a
blood transfusion (Anaemia)
• Underactive thyroid gland (Hypothyroidism)
• Feeling sick to the stomach (Nausea)
• Vomiting
• Frequent watery stools (Diarrhoea)
• Itchy skin
• Rash
• Fever
• Increased levels of substances in the blood produced by the liver which may
be a sign of liver injury
These side effects are considered common in patients who took dostarlimab (may
affect up to 1 in 10 people):
• Decreased production of adrenal hormones resulting in possible weakness
and/or low blood pressure
• Overactive thyroid gland
• Inflammation of the lungs which can cause shortness of breath and difficulty
breathing
• Inflammation of the pancreas causing pain in the upper abdomen. This could
become severe and cause nausea and vomiting, fever and rapid heart rate.
(Pancreatitis)
• Inflammation of the colon that can cause stomach pain or diarrhoea (Colitis)
• Muscle pain (Myalgia)
• Chills
The side effects listed below require immediate medical attention or advice.
Call the Investigator right away if you have any of these side effects.
• Respiratory: shortness of breath, rapid breathing, new or worse cough
• Gastrointestinal: diarrhoea, stools that are black or bloody, stomach area
pain, nausea or vomiting
• Kidneys: dark or bloody urine, urinating more often than usual
• Musculoskeletal: chest pain, muscle pain or weakness
• Cardiac: fast or unusual heartbeat
• Skin: rash, itching, blisters, pale or yellow skin
• Eyes: yellowing of the whites of your eyes, blurry vision
• Brain: abnormal thinking, confusion, personality changes, headache and neck
stiffness
• General: bleeding or bruising more easily than normal, feeling cold, hair
loss. dizziness or fainting, feeling tired or weak, fever or chills
For Study Drug: NIRAPARIB
As of March 2021, Niraparib has been studied in more than 2244 patients in
TESARO clinical trials. Niraparib capsule is marketed as ZEJULA® and is
approved to treat adult patients with recurrent epithelial ovarian, fallopian
tube, or primary peritoneal cancer in the United States and in Europe.
Niraparib is currently being studied as a single medication and as a
combination therapy in a variety of cancer clinical studies.
Niraparib Side Effects experienced by patients taking niraparib as a single
drug therapy:
Some of the side effects mentioned below can be life-threatening or fatal.
These side effects are considered very common in patients who took niraparib
(may affect more than 1 in 10 people):
• Decrease in a type of blood cells called platelets that help stop bleeding;
this may increase your risk of bleeding (thrombocytopenia)
• Decrease in red blood cells that carry oxygen; this may make you feel tired
or short of breath (anemia)
• Decrease in the number of white blood cells (leukopenia) that fight infection
• Decrease in a type of white blood cells called neutrophils that fight
infection; (neutropenia)
• Difficulty with emptying the bowels, often because of hard stools
(constipation)
• Feeling sick to your stomach (nausea)
• Vomiting
• Reduced desire to eat (decreased appetite)
• Pain in belly (abdominal pain)
• Frequent watery stools (diarrhea)
• Upset stomach/heartburn
• Sleeplessness, trouble sleeping
• Pain or burning and frequent urination which may indicate an infection
(urinary tract infection)
• Feeling weak (asthenia)
• Feeling tired, lack of energy (fatigue)
• Back pain
• Joint pain
• Breathlessness or difficulty breathing (dyspnea)
• Runny or stuffy nose (nose or upper throat infection)
• Increased blood pressure
• Feeling lightheaded or like you are about to faint (dizziness)
• Cough
• Headache
• Noticeably rapid, strong, or irregular heartbeat (palpitations)
These side effects are considered common in patients who took niraparib (may
affect up to 1 in 10 people):
• Infection due to low white blood cell count (neutropenic infection)
• Low blood cell counts due to a problem in the bone marrow or blood cancer
starting from the bone marrow (Myelodysplastic Syndrome [MDS]/Acute Myeloid
Leukemia [AML])
• Altered sense of taste; this means that foods might taste differently than
you are used to
• Reduced potassium in blood
• An abnormally rapid heart rate
• Dry mouth
• Feeling anxious (anxiety)
• Mood change to feeling sad/discouraged, listless (depression)
• Impaired concentration, understanding, memory and thinking (cognitive
impairment)
• Nosebleed
• Inflammation of the lining of the airways (bronchitis)
• Increased sensitivity of the skin to sunlight (photosensitivity)
• Rash
• Muscle pain
• An accumulation of fluid that causes swelling in the extremities such as
lower legs, hands, and feet
• Increased liver enzyme in the blood; this may be a sign of damage to liver
cells
• Increased level of creatinine in your blood; this may be a sign of kidney
damage
• Decrease in weight
• Infection of the white area of the eye
• Sore, irritated, red mouth
• Swelling or irritation of the lining of the mouth, throat, esophagus,
stomach, or intestines
• Allergic reaction (hypersensitivity, including anaphylaxis).
In addition to the above, the side effects below were reported by patients who
were prescribed niraparib by their doctors:
• Allergic reaction (hypersensitivity*, including anaphylaxis**).
• Life-threatening allergic reaction (such as difficulty breathing, rash,
localized swelling, such as tongue, throat or lips) (anaphylaxis*)
• Confusion (confusional state*: symptom that makes you feel as if you can't
think clearly. You might feel disoriented and have a hard time focusing or
making decisions)
• Seeing or hearing things that are not really there (hallucination**)
• Impaired concentration, understanding, memory* and thinking (cognitive
impairment*)
• Inflammation of the lungs which can cause shortness of breath and difficulty
breathing (non-infectious pneumonitis*)
*Observed frequency in clinical trials uncommon (may affect up to 1 in 100
people).
**No events reported in monotherapy clinical trials
Potential for new blood cancer called myelodysplastic syndrome and/or acute
myeloid leukemia (MDS/AML), a new primary cancer, embolic and/or thrombotic
events (blood clots):
• Niraparib belongs to a group of drugs called PARP inhibitors. This group of
drugs are suspected of causing new blood cancers known as myelodysplastic
syndrome (MDS) and acute myeloid leukemia (AML). Because niraparib is a PARP
inhibitor there is a potential risk of developing a new blood cancer leading to
leukemia.
• If you have had MDS or leukemia before entering this study, you are at
increased risk for developing leukemia again and must tell your Investigator
before starting this study.
• Although rare, patients in niraparib clinical trials have had MDS/AML. In a
randomized trial comparing niraparib to placebo (
Collegeville Rd 1250 S
Collegeville, PA 19426
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Collegeville Rd 1250 S
Collegeville, PA 19426
US
Listed location countries
Age
Inclusion criteria
Part 1 & Part 2
1. Female subject at least 18 years of age, who is able to understand the study
procedures and agrees to participate in the study by providing written informed
consent.
2. Subject has histologically or cytologically proven endometrial cancer with
recurrent or advanced disease.
3. Subject must provide adequate tumor tissue sample at Screening for MMR/MSI
status testing.
4. Subject must have primary Stage III or Stage IV disease or first recurrent
endometrial cancer with a low potential for cure by radiation therapy or
surgery alone or in combination, and meet at least 1 of the following criteria:
a. Subject has primary Stage IIIA to IIIC1 disease with presence of evaluable
or measurable disease per RECIST v.1.1 based on Investigator*s assessment.
Lesions that are equivocal or can be representative of post-operative change
should be biopsied and confirmed for the presence of tumor.
b. Subject has primary Stage IIIC1 disease with carcinosarcoma, clear cell,
serous, or mixed histology (containing >= 10% carcinosarcoma, clear cell, or
serous histology) regardless of presence of evaluable or measurable disease on
imaging.
c. Subject has primary Stage IIIC2 or Stage IV disease regardless of presence
of evaluable or measurable disease.
d. Subject has first recurrent disease and is chemotherapy naïve to systemic
anticancer therapy.
e. Subject has received prior neo-adjuvant/adjuvant systemic chemotherapy and
had a recurrence or PD >= 6 months after completing treatment (first recurrence).
5. Subject has an ECOG performance status of 0 or 1.
6. Subject has adequate organ function, defined as follows:
a. Absolute neutrophil count >= 1,500 cells/µL
b. Platelets >= 100,000 cells/µL
c. Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
d. Serum creatinine <= 1.5× upper limit of normal (ULN) or calculated CrCl >= 50
mL/min using the Cockcroft-Gault equation for subjects with creatinine levels <=
1.5× institutional ULN
e. Total bilirubin <= 1.5× ULN and direct bilirubin <= 1× ULN
f. AST and ALT <= 2.5× ULN unless liver metastases are present, in which case
they must be <= 5× ULN
g. International normalized ratio or prothrombin time (PT) <=1.5× ULN and
activated partial thromboplastin time <=1.5× ULN. Subjects receiving
anticoagulant therapy must have a PT or partial thromboplastin within the
therapeutic range of intended use of anticoagulants.
7. Contraceptive use by subjects should be consistent with local regulations
regarding the methods of contraception for those participating in clinical
studies.
A female participant is eligible to participate if she is not pregnant or
breastfeeding, and one of the following conditions applies:
The subject is a woman of nonchildbearing potential (WONCBP) OR The subject is
a woman of childbearing potential (WOCBP), using a contraceptive method that is
highly effective (with a failure rate of <1% per year and, preferably, with low
user dependency) during the Treatment Period and for at least 180 days after
the last dose of study treatment and agrees not to donate eggs (ova or oocytes)
for the purpose of reproduction during this period.
A WOCBP must have a negative highly sensitive pregnancy test (urine or serum,
as required by local guidelines) within 72 hours before the first dose of study
treatment. If a urine test cannot be confirmed as negative (eg, an ambiguous
result), a serum pregnancy test is required. In such cases, the participant
must be excluded from participation if the serum pregnancy result is positive.
Part 2 only:
8. Subjects must have normal BP or adequately treated and controlled
hypertension (systolic BP =140 mmHg and diastolic BP =90 mmHg).
9. Subjects must be able to take medication PO.
Exclusion criteria
Part 1 & Part 2:
1. Subject has received neo-adjuvant/adjuvant systemic anticancer therapy for
primary Stage III or IV disease and:
a. has not had a recurrence or PD prior to first dose on the study OR
b. has had a recurrence or PD within 6 months of completing systemic anticancer
therapy treatment prior to first dose onthe study Note: Low-dose cisplatin
given as a radiation sensitizer or hormonal therapies do not exclude subjects
from study participation.
2. Subject has had > 1 recurrence of endometrial cancer.
3. Subject has received prior therapy with an anti-PD-1, anti-PD-L1, or
anti-PD-L2 agent.
4. Subject has received prior anticancer therapy (chemotherapy, targeted
therapies, hormonal therapy, radiotherapy, or immunotherapy) within 21 days or
<5 times the half-life of the most recent therapy prior to Study Day 1,
whichever is shorter.
5. Subject has a concomitant malignancy, or subject has a prior non-endometrial
invasive malignancy who has been disease-free for <3 years or who received any
active treatment in the last 3 years for that malignancy. Non-melanoma skin
cancer is allowed.
6. Subject has known uncontrolled central nervous system metastases,
carcinomatosis meningitis, or both. Note: Subjects with previously treated
brain metastases may participate provided they are stable (without evidence of
PD by imaging [using the identical imaging modality for each assessment, either
MRI or CT scan] for at least 4 weeks prior to the first dose of study treatment
and any neurologic symptoms have returned to baseline), have no evidence of new
or enlarging brain metastases, and have not been using steroids for at least 7
days prior to study treatment. Carcinomatous meningitis precludes a subject
from study participation regardless of clinical stability.
7. Subject has a known history of human immunodeficiency virus HIV (HIV 1/2
antibodies).
8. Subject has known active hepatitis B (eg, hepatitis B surface antigen
reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid [qualitative]
is detected).
9. Subject has an active autoimmune disease that has required systemic
treatment in the past 2 years. Replacement therapy is not considered a form of
systemic therapy (eg, thyroid hormone or insulin)
10. Subject has a diagnosis of immunodeficiency or is receiving systemic
steroid therapy or any other form of systemic immunosuppressive therapy within
7 days prior to the first dose of study treatment.
11. Subject has not recovered (ie, to Grade <= 1 or to baseline) from cytotoxic
therapy-induced AEs or has received transfusion of blood products (including
platelets or red blood cells) or administration of colony-stimulating factors
(including granulocyte colony-stimulating factor [G-CSF], granulocyte
macrophage colony-stimulating factor [GM
CSF], or recombinant erythropoietin) within 21 days prior to the first dose of
study drug. Note: Subjects with Grade <= 2 neuropathy, Grade <= 2 alopecia, or
Grade <= 2 fatigue are an exception to this criterion and may qualify for the
study.
12. Subject has not recovered adequately from AEs or complications from any
major surgery prior to starting therapy.
13. Subject has a known hypersensitivity to carboplatin, paclitaxel, or
dostarlimab components or excipients.
14. Subject is currently participating and receiving study treatment or has
participated in a study of an investigational agent and received study
treatment or used an investigational device within 4 weeks of the first dose of
treatment.
15. Subject is considered a poor medical risk due to a serious, uncontrolled
medical disorder, nonmalignant systemic disease, or active infection requiring
systemic therapy. Specific examples include, but are not limited to, active,
noninfectious pneumonitis; uncontrolled ventricular arrhythmia; recent (within
90 days) myocardial infarction; uncontrolled major seizure disorder; unstable
spinal cord compression; superior vena cava syndrome; or any psychiatric or
substance abuse disorders that would interfere with cooperation with the
requirements of the study (including obtaining informed consent).
16. Subject is pregnant or breastfeeding or is expecting to conceive children
within the projected duration of the study, starting with the screening visit
through 180 days after the last dose of study treatment.
17. Subject has received, or is scheduled to receive, a live vaccine within 30
days before first dose of study treatment, during study treatment, and for up
to 180 days after receiving the last dose of study treatment.
Part 2 only:
18. Subject has received prior therapy with a PARP inhibitor.
19. Subject has clinically significant cardiovascular disease.
20. Subject has any known history or current diagnosis of myelodysplastic
syndrome or acute myeloid leukemia.
21. Subject is at increased bleeding risk due to concurrent conditions.
22. Subject has a known hypersensitivity to niraparib components or excipients.
23.Subject has participated in Part 1 of this study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-506551-23-00 |
| EudraCT | EUCTR2019-001576-11-NL |
| ClinicalTrials.gov | NCT03981796 |
| CCMO | NL70807.078.19 |