stop_circleTerminated/Withdrawn

Relapsed or refractory solid tumors or lymphoma in children, Neuroblastoma, Osteosarcoma, Rhabdomyosarcoma, Ewing sarcoma

Bayer Identifier:

19176

ClinicalTrials.gov Identifier:

NCT03458728

EudraCT Number:

2017-000383-15

EU CT Number:

Not Available
Safety, tolerability, efficacy and pharmacokinetics of copanlisib in pediatric patients

Trial 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.

Key Participants Requirements

Sex

All

Age

6 - 21 Years
  • -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, with measurable or evaluable disease, 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 disease (evaluable disease is acceptable for neuroblastoma and Ewing sarcoma). 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.

  • -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.

Trial summary

Enrollment Goal
31
Trial Dates
April 2018 - February 2023
Phase
Phase 1/Phase 2
Could I Receive a placebo
No
Products
Aliqopa (Copanlisib, BAY80-6946)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
The Children's HospitalAurora, 80045, United States
Completed
Children's Hospital of PhiladelphiaPhiladelphia, 19104, United States
Completed
St. Jude Children's Research HospitalMemphis, 38105, United States
Completed
Cincinnati Children's Hospital and Medical CenterCincinnati, 45229, United States
Completed
Dana-Farber Cancer InstituteBoston, 02215, United States
Completed
Columbia University Medical CenterNew York, 10032, United States
Completed
Children's Hospital of AlabamaBirmingham, 35233, United States
Completed
Children's Healthcare of AtlantaAtlanta, 30322, United States
Completed
Riley Hospital For ChildrenIndianapolis, 46202, United States
Completed
Seattle Children's HospitalSeattle, 98105, United States
Completed
Children's Hospital of Orange CountyOrange, 92868-3974, United States
Completed
Children's National Medical CenterWashington, 20010-2970, United States
Completed
Children's Hospital of Pittsburgh of UPMCPittsburgh, 15224, United States
Withdrawn
Ann & Robert H. Lurie Children's Hospital of ChicagoChicago, 60611, United States
Completed
Texas Children's HospitalHouston, 77030, United States
Withdrawn
University of Minnesota Medical CenterMinneapolis, 55455, United States
Withdrawn
C.S. Mott Children's HospitalAnn Arbor, 48109, United States
Withdrawn
Children's Hospital of Los AngelesLos Angeles, 90027-6089, United States
Withdrawn
Memorial Sloan-Kettering Cancer CenterNew York, 10065, United States
Withdrawn
University of Texas Southwestern Medical CenterDallas, 75390, United States
Withdrawn
Cook Children's Medical CenterFort Worth, 76104-2796, United States

Primary Outcome

  • The maximum tolerated dose (MTD)
    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.
    date_rangeTime Frame:
    Cycle 1 (28 days)
  • Dose-limiting Toxicities(DLTs)
    Phase 1
    date_rangeTime Frame:
    Cycle 1 (28 days)
  • Number of participants with Treatment-emergent Adverse Events(TEAEs)
    Phase 1
    date_rangeTime Frame:
    Approximately 13 months
  • Number of participants with Serious Adverse Events (SAEs)
    Phase 1
    date_rangeTime Frame:
    Approximately 13 months
  • Number of participants with Treatment-related Adverse Events (AEs).
    Phase 1
    date_rangeTime Frame:
    Approximately 13 months
  • Objective response rate (ORR)
    Phase 2:ORR is the primary efficacy variable in neuroblastoma, Ewing sarcoma and rhabdomyosarcoma.
    date_rangeTime Frame:
    Up to 31 months
  • Disease control rate (DCR)
    Phase 2:DCR is the primary efficacy variable in osteosarcoma.
    date_rangeTime Frame:
    Up to 31 months
  • Progression-free survival (PFS)
    Phase 2: PFS is considered as co-primary (descriptively evaluated) variable in patients with osteosarcoma.
    date_rangeTime Frame:
    Up to 31 months

Secondary Outcome

  • Copanlisib maximum drug concentration (Cmax)
    Phase 1.
    date_rangeTime Frame:
    Age ≥ 6 years: Pre-dose, Post-dose on Cycle 1 Day 1 and Day 15 (1-1 .25 hour (h), 1.5- 3h, 22-24h). Age< 6 years: Pre-dose, Post-dose on Cycle 1 Day 1 and Day 15 (1-1 .25h, 22-24h). Cycle length is 28 days.
  • Area under the curve (AUC(0-168))
    Phase 1
    date_rangeTime Frame:
    Age ≥ 6 years: Pre-dose, Post-dose on Cycle 1 Day 1 and Day 15 (1-1 .25 hour (h), 1.5- 3h, 22-24h). Age< 6 years: Pre-dose, Post-dose on Cycle 1 Day 1 and Day 15 (1-1 .25h, 22-24h). Cycle length is 28 days.
  • Objective response rate (ORR)
    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
    date_rangeTime Frame:
    Approximately 12 months
  • Duration of response (DOR)
    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
    date_rangeTime Frame:
    Up to 31 months
  • PFS in each indication except for osteosarcoma
    Phase 2: PFS is defined as the time from first dose of study drug 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).
    date_rangeTime Frame:
    Up to 31 months
  • Overall survival (OS)
    Phase 2: OS is defined as the time from first dose of study drug until death from any cause or until the last date the patient is known to be alive.
    date_rangeTime Frame:
    Up to 31 months
  • Number of participants with Treatment-emergent AEs
    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).
    date_rangeTime Frame:
    Up to 32 months
  • Number of participants with treatment emergent SAEs
    Phase 2: The severity of AEs will be graded using the NCI CTCAE v 4.03 dictionary
    date_rangeTime Frame:
    Up to 32 months
  • Number of participants with treatment-emergent clinically significant change in laboratory parameters, ECGs and vital signs
    Phase 2:The severity of AEs will be graded using the NCI CTCAE v 4.03 dictionary
    date_rangeTime Frame:
    Up to 32 months

Trial design

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
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Non-randomized
Blinding
N/A
Assignment
Parallel Assignment
Trial Arms
5

Additional Information

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