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Dose Escalation and Cohort Expansion Study of Niraparib and Dostarlimab in Paediatric Participants With Solid Tumours
EU CTIS ID: 2024-511071-16-00
What this study is testing
Part 1A: Establish the RP2D of the combination of niraparib tablet and dostarlimab in paediatric participants Part 1B: Establish the RP2D of the combination of niraparib tablet for oral suspension (TfOS) and dostarlimab in paediatric participants Part 2: Please refer to the separate cohort-specific supplements for this information.
- Human Pharmacology (Phase I)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Participant is child or adolescent ≥6 months to <18 years old at the time of informed consent/assent. If a participant is enrolled under Protocol Amendment 04, the participant must be ≥6 months to <8 years old at the time of informed consent/assent.
- Participant with disease other than neuroblastoma has radiologically measurable disease that can be tracked as RECIST v1.1. Participant with neuroblastoma has measurable/evaluable disease by International Neuroblastoma Response Criteria (INRC) at the time of study enrolment. Neuroblastoma participants with recurrent/relapsed bone metastasis that is MIBG-positive (or FDG positive, for MIBG-nonavid tumours) as only site of disease are eligible.
- Under Protocol Amendment 03 (or earlier), a participant in Part 1A must be able to swallow the "CCI" and have a baseline body weight of ≥20 kg. Participants in Part 1A who are unable to swallow the "CCI" or who have a baseline body weight <20 kg are eligible to receive "CCI" only. As of Protocol Amendment 04, there are no inclusion criteria addressing ability to swallow niraparib tablets.
- Performance status must be ≥60% on the Karnofsky scale for participants >16 years of age and ≥60% on the Lansky scale for participants ≤16 years of age. Note: Neurologic deficits in participants with brain metastases must have been stable for at least 7 days prior to study enrolment. Participants who are unable to walk because of paralysis, but who are upright in a wheelchair, will be considered ambulatory for the purpose of assessing the performance status.
- Participant has adequate organ function, defined as follows: a. absolute neutrophil count (ANC) ≥1000/μL b. platelets ≥100000/μL c. haemoglobin ≥8 g/dL or ≥5.0 mmol/L d. serum creatinine ≤1.5 × upper limit of normal (ULN) for age or calculated creatinine clearance or radioisotope glomerular filtration rate ≥60 mL/min/1.73 m2 e. total bilirubin ≤1.5 × ULN or direct bilirubin ≤1 × ULN f. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN unless liver metastases are present, in which case AST and ALT must be ≤5 × ULN g. international normalised ratio or prothrombin time (PT) ≤1.5 × ULN unless the participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants h. activated PTT ≤1.5 × ULN unless the participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the conditions per protocol.
You likely can't join if
- Participation presents unacceptable risk to the prospective participant based on the Investigator's judgment.
- Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- Participant has a known history of HIV (type 1 or 2 antibodies).
- Participant has documented presence of HbsAg and/or HBcAb at Screening or within 3 months prior to first dose of study intervention. Participants with a negative HbsAg and positive HbcAb result are eligible only if HBV DNA is negative.
- Participant must not have a gastrointestinal condition, such as bowel obstruction, that can impact absorption of oral medications and is identified by clinical symptoms or CT scan, etc.
- Participant has had any known Grade 3 or 4 anaemia, neutropenia, and/or thrombocytopenia that was related to the most recent prior anticancer treatment and that persisted >4 weeks (28 days).
See the full eligibility criteria
Who can join
- Participant is child or adolescent ≥6 months to <18 years old at the time of informed consent/assent. If a participant is enrolled under Protocol Amendment 04, the participant must be ≥6 months to <8 years old at the time of informed consent/assent.
- Participant with disease other than neuroblastoma has radiologically measurable disease that can be tracked as RECIST v1.1. Participant with neuroblastoma has measurable/evaluable disease by International Neuroblastoma Response Criteria (INRC) at the time of study enrolment. Neuroblastoma participants with recurrent/relapsed bone metastasis that is MIBG-positive (or FDG positive, for MIBG-nonavid tumours) as only site of disease are eligible.
- Under Protocol Amendment 03 (or earlier), a participant in Part 1A must be able to swallow the "CCI" and have a baseline body weight of ≥20 kg. Participants in Part 1A who are unable to swallow the "CCI" or who have a baseline body weight <20 kg are eligible to receive "CCI" only. As of Protocol Amendment 04, there are no inclusion criteria addressing ability to swallow niraparib tablets.
- Performance status must be ≥60% on the Karnofsky scale for participants >16 years of age and ≥60% on the Lansky scale for participants ≤16 years of age. Note: Neurologic deficits in participants with brain metastases must have been stable for at least 7 days prior to study enrolment. Participants who are unable to walk because of paralysis, but who are upright in a wheelchair, will be considered ambulatory for the purpose of assessing the performance status.
- Participant has adequate organ function, defined as follows: a. absolute neutrophil count (ANC) ≥1000/μL b. platelets ≥100000/μL c. haemoglobin ≥8 g/dL or ≥5.0 mmol/L d. serum creatinine ≤1.5 × upper limit of normal (ULN) for age or calculated creatinine clearance or radioisotope glomerular filtration rate ≥60 mL/min/1.73 m2 e. total bilirubin ≤1.5 × ULN or direct bilirubin ≤1 × ULN f. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN unless liver metastases are present, in which case AST and ALT must be ≤5 × ULN g. international normalised ratio or prothrombin time (PT) ≤1.5 × ULN unless the participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants h. activated PTT ≤1.5 × ULN unless the participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the conditions per protocol.
What rules you out
- Participation presents unacceptable risk to the prospective participant based on the Investigator's judgment.
- Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- Participant has a known history of HIV (type 1 or 2 antibodies).
- Participant has documented presence of HbsAg and/or HBcAb at Screening or within 3 months prior to first dose of study intervention. Participants with a negative HbsAg and positive HbcAb result are eligible only if HBV DNA is negative.
- Participant must not have a gastrointestinal condition, such as bowel obstruction, that can impact absorption of oral medications and is identified by clinical symptoms or CT scan, etc.
- Participant has had any known Grade 3 or 4 anaemia, neutropenia, and/or thrombocytopenia that was related to the most recent prior anticancer treatment and that persisted >4 weeks (28 days).
- Exclusion criteria for Part 2 of the study are described in each cohort-specific supplement
- Participant has known hypersensitivity to dostarlimab or niraparib, their components, or their excipients
- Participant has a known history of myelodysplastic syndrome or acute myeloid leukaemia.
- Participant has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying antirheumatic drugs, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- Participant has known active CNS metastases, carcinomatous meningitis, or both. Note: Participants with previously treated brain metastases may participate provided they are clinically stable and have no evidence of new, enlarging, or progressing brain metastases (using the identical imaging modality for each assessment, either MRI or CT scan) for at least 4 weeks (28 days) prior to the first dose of study treatment. In addition, the participant must not have been using steroids for at least 7 days prior to the first dose of study treatment. Carcinomatous meningitis precludes a participant from study participation regardless of clinical stability.
- Participant had a known additional (second primary) malignancy that progressed or required active treatment within the last 2 years
- Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active infection that requires systemic therapy. Specific examples include, but are not limited to, history of (noninfectious) pneumonitis that required steroids or current pneumonitis, uncontrolled ventricular arrhythmia, 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 assent/consent).
- Participant has a condition (such as transfusion-dependent anaemia or thrombocytopenia), requirement for therapy, or laboratory abnormality that might confound the study results or interfere with the participant’s participation for the full duration of the study treatment
- Participant is pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with the Screening Visit through 180 days after the last dose of study treatment. No data are available regarding the presence of dostarlimab or niraparib or its metabolites in human milk, or on its effects on the breastfed infant or milk production. Because of the potential for serious adverse reactions in breastfed infants from dostarlimab and/or niraparib, female participants should not breastfeed during treatment with dostarlimab and/or niraparib and for at least 4 months after the last dose of dostarlimab or at least 30 days after the last dose of niraparib, whichever is longer.
The study team makes the final eligibility decision.
Where it's taking place
- United Kingdom
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 0-17 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United Kingdom. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.