Clinical Trials /

Safety, Tolerability, Efficacy and Pharmacokinetics of Copanlisib in Pediatric Patients

NCT03458728

Description:

This study is designed to investigate whether the use of copanlisib is safe, feasible and beneficial to pediatric patients with solid solid tumors or lymphoma that are recurrent or refractory to standard therapy.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety, Tolerability, Efficacy and Pharmacokinetics of Copanlisib in Pediatric Patients
  • Official Title: A Non-randomized, Open-label, Multi-center, Phase I/II Study of Phosphatidylinositol-3-kinase (PI3K) Inhibitor Copanlisib in Pediatric Patients With Relapsed/Refractory Solid Tumors or Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 19176
  • SECONDARY ID: 2017-000383-15
  • NCT ID: NCT03458728

Conditions

  • Mixed Tumor, Malignant

Interventions

DrugSynonymsArms
BAY806946Dose escalation of BAY806946 in Phase 1

Purpose

This study is designed to investigate whether the use of copanlisib is safe, feasible and beneficial to pediatric patients with solid solid tumors or lymphoma that are recurrent or refractory to standard therapy.

Trial Arms

NameTypeDescriptionInterventions
Dose escalation of BAY806946 in Phase 1ExperimentalIt is estimated that 2 or 3 dose cohorts may be evaluated in phase 1 of the study. Safety and MTD/RP2D dose will be evaluated in 2 age groups (< 1 year old and ≥ 1 year old).
  • BAY806946
Patients with Neuroblastoma in Phase 2ExperimentalRecommended Phase 2 dose (RP2D) for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.
  • BAY806946
Patients with Osteosarcoma in Phase 2ExperimentalRP2D for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.
  • BAY806946
Patients with Rhabdomyosarcoma in Phase 2ExperimentalRP2D for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.
  • BAY806946
Patients with Ewing sarcoma in Phase 2ExperimentalRP2D for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.
  • BAY806946

Eligibility Criteria

        Inclusion Criteria:

          -  Signed informed consent form by patients and/or patients' parents/legal guardians and
             age appropriate assent form by the patients obtained before any study specific
             procedure

          -  Male or female patients from 6 months to ≤ 21 years old at the time of study
             enrollment

          -  Confirmation of diagnosis:

               -  Phase I: Patients must have histologic verification of a solid tumor or lymphoma
                  malignancy at diagnosis for which there is no standard curative anti-cancer
                  treatment or treatment is no longer effective and must have received ≥ 1 prior
                  line of therapy.

               -  Phase II: patients must have histologically verified tumor at initial diagnosis
                  and radiologically or histologically confirmed status at inclusion as indicated
                  in the following: neuroblastoma, osteosarcoma, rhabdomyosarcoma or Ewing sarcoma.

               -  Patients with solid tumors must have measurable or evaluable (for neuroblastoma
                  and Ewing sarcoma) disease. Tumor assessment will be done via computed tomography
                  (CT), magnetic resonance imaging (MRI) or positron emission tomography-computed
                  tomography (PET-CT). Tumor lesions situated in a previously irradiated area, or
                  in an area subjected to other loco-regional therapy, may be considered measurable
                  if there has been demonstrated progression in the lesion. Bone scans (if
                  clinically indicated) should be obtained within ≤ 4 weeks prior to the start of
                  treatment.

          -  Performance level: Lansky ≥ 50% for patients ≤ 16 years of age and Karnofsky ≥ 50% for
             patients > 16 years of age.

          -  Adequate bone marrow, renal and liver function.

        Exclusion Criteria:

          -  Active or uncontrolled infection (National Cancer Institute (NCI)-CTCAE Grade ≥ 2).

          -  History or concurrent condition of interstitial lung disease of any severity and/or
             severely impaired lung function (as judged by the investigator).

          -  Diabetes mellitus.

          -  Uncontrolled arterial hypertension despite optimal medical management (per
             institutional guidelines).

          -  Patients with central nervous system (CNS) malignancies.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:6 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The maximum tolerated dose (MTD)
Time Frame:Approximately 8 months
Safety Issue:
Description:Phase 1: The highest dose level of copanlisib that can be given so that not more than 1 out of 6 patients experience a DLT during the DLT evaluation period.

Secondary Outcome Measures

Measure:Copanlisib maximum drug concentration (Cmax)
Time Frame:Cycle 1 Day 1 and Day 15
Safety Issue:
Description:Phase 1.
Measure:Area under the curve (AUC(0-168))
Time Frame:Cycle 1 Day 1 and Day 15
Safety Issue:
Description:Phase 1
Measure:Objective response rate (ORR)
Time Frame:Approximately 12 months
Safety Issue:
Description:Phase 1: ORR by dose cohort is defined as the number of responders divided by the number of patients in full analysis set (FAS) in the indication
Measure:Duration of response (DOR)
Time Frame:Up to 31 months
Safety Issue:
Description:Phase 2: DOR is defined as the time from the date of first observed tumor response (Complete response (CR) or Partial response (PR)) until first subsequent disease progression or until death (if death occurs before progression is documented) due to any cause
Measure:PFS in each indication except for osteosarcoma
Time Frame:Up to 31 months
Safety Issue:
Description:Phase 2: PFS is defined as the time from enrollment (i.e., date of treatment assignment) to disease progression according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST1.1) for solid tumor patients (except osteosarcoma) and SIOPEN or Curie score for neuroblastoma patients with Iodine-123 metaiodobenzylguanidine (MIBG)-avid disease, or death (if death occurs before progression is documented).
Measure:Overall survival (OS)
Time Frame:Up to 31 months
Safety Issue:
Description:Phase 2: OS is defined as the time from enrollment (i.e., date of treatment assignment) until death from any cause or until the last date the patient is known to be alive.
Measure:Number of participants with Treatment-emergent AEs
Time Frame:Up to 32 months
Safety Issue:
Description:Phase 2: A treatment emergent AE is defined as any event arising or worsening after start of test drug administration until 30 days after the last dose of the study drug intake (end of safety followup).
Measure:Number of participants with treatment emergent SAEs
Time Frame:Up to 32 months
Safety Issue:
Description:Phase 2: The severity of AEs will be graded using the NCI CTCAE v 4.03 dictionary
Measure:Number of participants with treatment-emergent clinically significant change in laboratory parameters, ECGs or vital signs
Time Frame:Up to 32 months
Safety Issue:
Description:Phase 2:The severity of AEs will be graded using the NCI CTCAE v 4.03 dictionary

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bayer

Trial Keywords

  • Phase I: relapsed or refractory solid tumors or lymphoma
  • Phase II: relapsed or refractory solid tumors (neuroblastoma, osteosarcoma, rhabdomyosarcoma or Ewing sarcoma)

Last Updated

November 18, 2019