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Trial record 1 of 1 for:    GSK 213406
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Dose Escalation and Cohort Expansion Study of Niraparib and Dostarlimab in Pediatric Participants With Solid Tumors (SCOOP)

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ClinicalTrials.gov Identifier: NCT04544995
Recruitment Status : Recruiting
First Posted : September 10, 2020
Last Update Posted : October 7, 2021
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Description
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Brief Summary:
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 pediatric 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 pediatric participants with recurrent or refractory solid tumors.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Niraparib Drug: Dostarlimab Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 116 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: In Part 1 (dose escalation phase), the RP2D of the combination of niraparib and dostarlimab will be determined. This will be followed by Part 2 (dose expansion [DE] phase), in which the RP2D established in Part 1 will be evaluated for efficacy and safety in disease-specific expansion cohorts (osteosarcoma and neuroblastoma).
Masking: None (Open Label)
Masking Description: This will be an open-label study.
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 6, 2020
Estimated Primary Completion Date : March 21, 2030
Estimated Study Completion Date : September 5, 2030

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Participants receiving Niraparib +Dostarlimab
Participants will receive Niraparib and Dostarlimab.
 Drug: Niraparib
Niraparib will be administered

Drug: Dostarlimab
Dostarlimab will be administered.


Outcome Measures
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Primary Outcome Measures :
  1. Part 1A: Number of participants with dose limiting toxicities (DLTs) [ Time Frame: Up to 42 days from start of the treatment (Day 0) ]
    Number of participants with DLTs will be reported.

  2. Part 1B: Number of participants with DLTs [ Time Frame: Up to 42 days from start of the treatment (Day 0) ]
    Number of participants with DLTs will be reported.

  3. Part 2: Progression-free survival rate at 6 months (PFS6) in participants with osteosarcoma [ Time Frame: Up to 6 months from start of the treatment (Day 0) ]
    PFS6 is defined as the proportion of participants without progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria or death at 6 months from the date of the first dose of study treatment.

  4. Part 2: Overall response rate (ORR) in participants with neuroblastoma [ Time Frame: Up to 2 years from start of the treatment (Day 0) ]
    ORR is defined as the proportion of participants who have a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) as determined by the Investigator using International Neuroblastoma Response Criteria (INRC).


Secondary Outcome Measures :
  1. ORR [ Time Frame: Up to 2 years from start of the treatment (Day 0) ]
    ORR based on Investigator assessment is defined as the proportion of participants with a BOR of confirmed CR or PR as determined by the Investigator using RECIST v1.1 criteria or INRC (for participants with neuroblastoma only).

  2. Duration of response (DOR) [ Time Frame: Up to 2 years from start of the treatment (Day 0) ]
    DOR is defined as the time from first documentation of response (CR or PR) until the time of first documented PD by RECIST v1.1 or INRC (for participants with neuroblastoma only) based on Investigator assessment or death (whichever occurs first).

  3. Disease control rate (DCR) in participants [ Time Frame: Up to 2 years from start of the treatment (Day 0) ]
    DCR is defined as the proportion of participants who have achieved a BOR of confirmed CR, confirmed PR, or stable disease by RECIST v1.1 or INRC (for participants with neuroblastoma only) based on Investigator assessment.

  4. PFS in participants [ Time Frame: Up to 2 years from start of the treatment (Day 0) ]
    PFS is defined as the time from the date of the first dose of study treatment to the first documented PD, as determined by RECIST v1.1 or INRC (for participants with neuroblastoma only) based on Investigator assessment, or death from any cause (whichever occurs first).

  5. Number of participants with Treatment emergent adverse events (TEAEs), adverse events (AEs, Serious AEs (SAEs), immune-related AEs (irAEs), TEAEs leading to death and AEs leading to discontinuation [ Time Frame: Up to 5 years ]
    TEAEs, AEs, SAEs, irAEs, TEAEs leading to death and AEs leading to discontinuation will be collected.

  6. Plasma concentration of niraparib [ Time Frame: Up to Cycle 1 Week 2 (Each Cycle of 21 days) ]
    Blood samples will be collected for the concentrations of niraparib.

  7. Serum concentration of dostarlimab [ Time Frame: Up to 2 years from start of the treatment (Day 0) ]
    Blood samples will be collected for the concentrations of dostarlimab.

  8. Number of participants compliant based on 'Acceptability and Palatability questionnaire' [ Time Frame: At Cycle 1 Week 1 (Each Cycle of 21 days) ]
    Participants will be assessed on Acceptability and Palatability questionnaire


Eligibility Criteria
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Ages Eligible for Study:   6 Months to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 will receive niraparib tablet or age-appropriate oral liquid formulation based on body weight and ability to swallow tablet.
  • 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.

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]) 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 prior to enrolment and must not be eligible for local curative treatment. 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 BRCA1/2 and other homologous recombination DNA repair (HRR) pathway genes, mutational signatures including signature 3, and tumor mutational burden (TMB).

For Part 2 (osteosarcoma expansion cohort) only:

  • Participant has recurrent or refractory osteosarcoma and must not be eligible for local curative treatment.
  • Participant has radiographically measurable disease that can be tracked as RECIST v1.1 target lesion(s).
  • Participant must provide tumor tissue sample at screening for retrospective exploratory biomarker analysis.

For Part 2 (neuroblastoma expansion cohort) only:

  • Participant has recurrent or refractory neuroblastoma and must not be eligible for local curative treatment.
  • Participant has radiographically measurable disease at the time of study enrolment; participants with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine-positive (+) evaluable disease are eligible. Measurable disease in participants with CNS involvement is defined as a tumor that is measurable in 2 perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than 1 slice.
  • Participant must provide tumor tissue sample at screening.

Exclusion Criteria:

For Part 1 and Part 2 (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 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), 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 including the following: Participants who received a transfusion (platelets or red blood cells) within 6 weeks of the first dose of study treatment are not eligible. Participants who received colony-stimulating factors (e.g., granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks prior to the first dose of study treatment are not eligible.
  • 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 known active hepatitis B (e.g., hepatitis B surface antigen reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid [qualitative] is detected).
  • Participant has had any known Grade 3 or 4 anemia, neutropenia, or thrombocytopenia due to prior chemotherapy that persisted >4 weeks related to the most recent prior treatment.
  • Participant had treatment with prior systemic anticancer therapy within the 3 weeks 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 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 >480 milliseconds at screening.
  • For Part 2 (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).
Contacts and Locations
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04544995


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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France
GSK Investigational Site Recruiting
Lille, France, 59000
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Sandra Raimbault         
GSK Investigational Site Recruiting
Lyon, France, 69008
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Nadège Corradini         
GSK Investigational Site Recruiting
Marseille, France, 13005
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Nicolas André         
GSK Investigational Site Recruiting
Paris cedex 05, France, 75248
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: François Doz         
GSK Investigational Site Recruiting
Paris, France, 75012
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Arnaud Petit         
GSK Investigational Site Recruiting
Villejuif, France, 94805
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Birgit Geoerger         
Spain
GSK Investigational Site Recruiting
Barcelona, Spain, 08035
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Lucas Moreno Martin         
GSK Investigational Site Recruiting
Esplugues De Llobregat. Barcelona, Spain, 08950
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Jaume Mora Graupera         
GSK Investigational Site Recruiting
Madrid, Spain, 28009
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Alba Rubio San Simón         
GSK Investigational Site Recruiting
Madrid, Spain, 28046
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Pilar Guerra Garcia         
GSK Investigational Site Recruiting
Valencia, Spain, 46026
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Antonio Juan Ribelles         
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
More Information
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04544995    
Other Study ID Numbers: 213406
First Posted: September 10, 2020    Key Record Dates
Last Update Posted: October 7, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by GlaxoSmithKline:
Dose escalation
Dose Expansion
Dostarlimab
 Niraparib
Osteosarcoma
Neuroblastoma
Additional relevant MeSH terms:
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Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents