Dose Escalation and Cohort Expansion Study of Niraparib and Dostarlimab in Paediatric Participants With Solid Tumours
- Conditions
- Solid TumoursMedDRA version: 21.1Level: LLTClassification code: 10065147Term: Malignant solid tumor Class: 10029104MedDRA version: 21.1Level: LLTClassification code: 10065252Term: Solid tumor Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2024-511071-16-00
- Lead Sponsor
- Glaxosmithkline Research & Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 147
Participant is child or adolescent =6 months to <18 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-PET positive, for MIBG-nonavid tumors) as only site of disease are eligible., In order to be eligible to receive the niraparib tablet formulation, participant must be able to swallow the 100 mg niraparib tablet and have a baseline body weight of =20 kg. Participants who are unable to swallow the 100 mg niraparib tablet or who have a baseline body weight <20 kg are eligible to receive the niraparib AAOLF only., 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) =1,000/µL b. platelets =100,000/µL c. haemoglobin =9 g/dL or =5.6 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.
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 known active hepatitis B (eg, hepatitis B surface antigen reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid [qualitative] is detected)., 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, 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 (ie, with use of disease-modifying antirheumatic drugs, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, 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 (without evidence of progression 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 the first dose of study treatment. Carcinomatous meningitis precludes a participant from study participation regardless of clinical stability., Participant had a known additional 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), 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 dose. No data are available regarding the pr
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method