Informations générales (source: ClinicalTrials.gov)
A PHASE 1, MULTICENTRE, OPEN-LABEL, DOSE-ESCALATION AND COHORT EXPANSION STUDY OF NIRAPARIB AND DOSTARLIMAB IN PAEDIATRIC PATIENTS WITH RECURRENT OR REFRACTORY SOLID TUMOURS
Interventional
Phase 1
GlaxoSmithKline (Voir sur ClinicalTrials)
octobre 2020
mai 2030
09 octobre 2024
This study will evaluate the combination of a poly (adenosine diphosphate-ribose)
polymerase (PARP) inhibitor, niraparib, with the programmed cell death protein 1 (PD-1)
inhibitor, dostarlimab in the paediatric population. This study will be conducted to
determine the recommended Phase 2 dose (RP2D) and evaluate the pharmacokinetics (PK),
safety, and efficacy of niraparib in combination with dostarlimab in paediatric
participants with recurrent or refractory solid tumors.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/12/2024 12:44:19 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Pablo BERLANGA | 22/02/2024 09:15:42 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| GSK Investigational Site - 13005 - Marseille - France | US GSK Clinical Trials Call Center | Contact (sur clinicalTrials) | |||
| GSK Investigational Site - 59000 - Lille - France | US GSK Clinical Trials Call Center | Contact (sur clinicalTrials) | |||
| GSK Investigational Site - 69008 - Lyon - France | US GSK Clinical Trials Call Center | Contact (sur clinicalTrials) | |||
| GSK Investigational Site - 75012 - Paris cedex 12 - France | US GSK Clinical Trials Call Center | Contact (sur clinicalTrials) | |||
| GSK Investigational Site - 75248 - Paris - France | US GSK Clinical Trials Call Center | Contact (sur clinicalTrials) | |||
| GSK Investigational Site - 94805 - Villejuif - France | US GSK Clinical Trials Call Center | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
For Part 1 and Part 2 (osteosarcoma and neuroblastoma expansion cohorts):
- Participant is a child or an adolescent greater than or equal to (>=) 6 months to
less than (<) 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 INRC at the time of study enrolment. Neuroblastoma
participants with recurrent/relapsed bone metastasis that is metaiodobenzylguanidine
(MIBG)-positive (or FDG-PET positive, for MIBG-nonavid tumors) as only site of
disease are eligible.
- Performance status must be >=60 percent on the Karnofsky scale for participants >16
years of age and >=60 percent on the Lansky scale for participants less than or
equal to (<=) 16 years of age.
- Participant has adequate organ function.
- A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies: Is not a woman
of childbearing potential (WOCBP) or Is a WOCBP and using a contraceptive method
that is highly effective.
- A male participant of reproductive potential is eligible to participate if he agrees
to refrain from donating sperm plus, either be abstinent from heterosexual
intercourse or must agree to use a male condom starting with the first dose of study
treatment through at least 90 days after the last dose of study treatment.
For Part 1 only:
• Participant has recurrent or refractory osteosarcoma, neuroblastoma, adrenocortical
carcinoma, Ewing sarcoma, rhabdomyosarcoma, or any other solid tumor (excluding tumors of
the central nervous system [CNS]) and must not be eligible for alternative curative
treatment: i. Participants with non-CNS solid tumours other than osteosarcoma,
neuroblastoma, adrenocortical carcinoma, Ewing sarcoma or rhabdomyosarcoma are required
to have prior documented breast cancer susceptibility gene (BRCAness) mutational
signature (mutational signature 3) on deoxyribonucleic acid (DNA) sequencing of tumor
obtained in the relapsed/recurrent disease setting, within 6 (preferably 3) months of
Cycle 1 Day 1.
ii. For participants with documented BRCAness mutational signature: Existing information
on molecular profiling of the participant's tumor tissue must be through a molecular
profiling platform such as Individualized Therapy for Relapsed Malignancies in Childhood
(INFORM). Molecular profile information must contain information from whole exome
sequencing or whole genome sequencing, including the mutation status of BRCA1 and BRCA 2
and other homologous recombination DNA repair (HRR) pathway genes, mutational signatures
including mutational signature 3, and tumor mutational burden (TMB).
iii. NOTE: Participants with recurrent or refractory osteosarcoma, neuroblastoma,
adrenocortical carcinoma, Ewing sarcoma, or rhabdomyosarcoma are asked to provide
documentation, if available, of the BRCAness mutational signature analysis on DNA
sequencing of their tumour.
For Part 2 Safety Run-in osteosarcoma participants and Part 2A (osteosarcoma expansion
cohort):
- Participant has recurrent or refractory osteosarcoma and must not be eligible for
alternative curative treatment. Documentation of BRCAness mutational signature 3
will be requested, but not required, for enrollment.
- Participant must confirm at screening that an archival or fresh tumor tissue sample
is available for use, in retrospective exploratory biomarker analysis. Otherwise,
enrolling site must discuss with Sponsor.
For Part 2 Safety Run-in neuroblastoma participants and Part 2B (neuroblastoma expansion
cohort):
- Participant has recurrent or refractory neuroblastoma and must not be eligible for
alternative curative treatment. Documentation of BRCAness mutational signature 3
will be requested, but not required, for enrollment.
- Participant must confirm at screening that an archival or fresh tumor tissue sample
is available for use, in retrospective exploratory biomarker analysis. Otherwise,
enrolling site must discuss with Sponsor.
For Part 1 and Part 2 (osteosarcoma and neuroblastoma expansion cohorts):
- Participant is a child or an adolescent greater than or equal to (>=) 6 months to
less than (<) 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 INRC at the time of study enrolment. Neuroblastoma
participants with recurrent/relapsed bone metastasis that is metaiodobenzylguanidine
(MIBG)-positive (or FDG-PET positive, for MIBG-nonavid tumors) as only site of
disease are eligible.
- Performance status must be >=60 percent on the Karnofsky scale for participants >16
years of age and >=60 percent on the Lansky scale for participants less than or
equal to (<=) 16 years of age.
- Participant has adequate organ function.
- A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies: Is not a woman
of childbearing potential (WOCBP) or Is a WOCBP and using a contraceptive method
that is highly effective.
- A male participant of reproductive potential is eligible to participate if he agrees
to refrain from donating sperm plus, either be abstinent from heterosexual
intercourse or must agree to use a male condom starting with the first dose of study
treatment through at least 90 days after the last dose of study treatment.
For Part 1 only:
• Participant has recurrent or refractory osteosarcoma, neuroblastoma, adrenocortical
carcinoma, Ewing sarcoma, rhabdomyosarcoma, or any other solid tumor (excluding tumors of
the central nervous system [CNS]) and must not be eligible for alternative curative
treatment: i. Participants with non-CNS solid tumours other than osteosarcoma,
neuroblastoma, adrenocortical carcinoma, Ewing sarcoma or rhabdomyosarcoma are required
to have prior documented breast cancer susceptibility gene (BRCAness) mutational
signature (mutational signature 3) on deoxyribonucleic acid (DNA) sequencing of tumor
obtained in the relapsed/recurrent disease setting, within 6 (preferably 3) months of
Cycle 1 Day 1.
ii. For participants with documented BRCAness mutational signature: Existing information
on molecular profiling of the participant's tumor tissue must be through a molecular
profiling platform such as Individualized Therapy for Relapsed Malignancies in Childhood
(INFORM). Molecular profile information must contain information from whole exome
sequencing or whole genome sequencing, including the mutation status of BRCA1 and BRCA 2
and other homologous recombination DNA repair (HRR) pathway genes, mutational signatures
including mutational signature 3, and tumor mutational burden (TMB).
iii. NOTE: Participants with recurrent or refractory osteosarcoma, neuroblastoma,
adrenocortical carcinoma, Ewing sarcoma, or rhabdomyosarcoma are asked to provide
documentation, if available, of the BRCAness mutational signature analysis on DNA
sequencing of their tumour.
For Part 2 Safety Run-in osteosarcoma participants and Part 2A (osteosarcoma expansion
cohort):
- Participant has recurrent or refractory osteosarcoma and must not be eligible for
alternative curative treatment. Documentation of BRCAness mutational signature 3
will be requested, but not required, for enrollment.
- Participant must confirm at screening that an archival or fresh tumor tissue sample
is available for use, in retrospective exploratory biomarker analysis. Otherwise,
enrolling site must discuss with Sponsor.
For Part 2 Safety Run-in neuroblastoma participants and Part 2B (neuroblastoma expansion
cohort):
- Participant has recurrent or refractory neuroblastoma and must not be eligible for
alternative curative treatment. Documentation of BRCAness mutational signature 3
will be requested, but not required, for enrollment.
- Participant must confirm at screening that an archival or fresh tumor tissue sample
is available for use, in retrospective exploratory biomarker analysis. Otherwise,
enrolling site must discuss with Sponsor.
For Part 1 and Part 2 (Safety Run-in and osteosarcoma and neuroblastoma expansion
cohorts):
- Participant has known hypersensitivity to dostarlimab or niraparib, their
components, or their excipients.
- Participant has a known history of myelodysplastic syndrome (MDS) or acute myeloid
leukemia (AML).
- Participant has active autoimmune disease that has required systemic treatment in
the past 2 years (that is [i.e.], with use of disease-modifying anti-rheumatic
drugs, corticosteroids, or immunosuppressive drugs). Replacement therapy (for
example [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.
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, non-malignant systemic disease, or active infection that requires systemic
therapy.
- Participant has a condition (such as transfusion-dependent anemia 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 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 human immunodeficiency virus (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 anemia, neutropenia, and/or
thrombocytopenia that was related to the most recent prior anti-cancer treatment and
that persisted >4 weeks (28 days).
- Participant has not recovered (i.e., to Grade ≤1 or to baseline) from systemic
anticancer therapy-induced AEs.
- Participant had toxicity related to prior immunotherapy that led to study treatment
discontinuation.
- Participant had treatment with systemic anticancer therapy (investigational agent or
device, or approved chemotherapy, targeted therapy, immunotherapy, or other systemic
therapy) within 3 weeks or 5 half-lives, whichever is shorter, prior to the first
dose of study treatment, radiation therapy encompassing >20 percent of the bone
marrow within 2 weeks prior to the first dose of study treatment, or any radiation
therapy within 1 week prior to the first dose of study treatment.
- Participant has not recovered adequately from AEs or complications from any major
surgery prior to starting study treatment.
- Participant has received a live vaccine within 30 days of planned start of study
treatment.
- Participant has clinically significant cardiovascular disease (e.g., significant
cardiac conduction abnormalities, uncontrolled hypertension, cardiac arrhythmia or
unstable angina, New York Heart Association Grade 2 or greater congestive heart
failure, serious cardiac arrhythmia requiring medication, and history of
cerebrovascular accident) within 6 months of enrolment.
- Participant has heart rate-corrected QT interval prolongation at screening >450
milliseconds (msec) or >480 msec for participants with bundle branch block.
- Participant has received a solid organ transplant.
- Participant has a documented presence of HCV antibody at Screening or within 3
months prior to first dose of study intervention. NOTE: Participants with a positive
HCV antibody test result due to prior resolved disease can be enrolled, if a
confirmatory HCV RNA test is negative and the participant otherwise meets entry
criteria.
- Participant has a documented presence of HCV RNA at Screening or within 3 months
prior to first dose of study intervention. NOTE: The HCV RNA test is optional and
participants with negative HCV antibody test are not required to undergo HCV RNA
testing as well.
For Part 2 (Safety Run-in, osteosarcoma expansion cohort, and neuroblastoma expansion
cohort):
- Participant has received prior therapy with an anti-PD-1, anti-programmed cell death
ligand 1, anti-programmed cell death-ligand 2, anti-cytotoxic
T-lymphocyte-associated antigen-4 antibody (including ipilimumab), or any other
antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
(with the exception of participants rolling over from Part 1 of the study: these
participants are allowed to have received dostarlimab).
- Participant has had prior treatment with a known poly(adenosine diphosphate-ribose)
polymerase (PARP) inhibitor (with the exception of participants rolling over from
Part 1 of the study: these participants are allowed to have received niraparib).