Terminated/Withdrawn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

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, 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.
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.

Trial summary

Enrollment Goal

Trial Dates

April 2018 - February 2023

Phase

Phase 1/Phase 2

Could I Receive a placebo

Products

Aliqopa (Copanlisib, BAY80-6946)

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed	The Children's Hospital	Aurora, 80045, United States
Completed	Children's Hospital of Philadelphia	Philadelphia, 19104, United States
Completed	St. Jude Children's Research Hospital	Memphis, 38105, United States
Completed	Cincinnati Children's Hospital and Medical Center	Cincinnati, 45229, United States
Completed	Dana-Farber Cancer Institute	Boston, 02215, United States
Completed	Columbia University Medical Center	New York, 10032, United States
Completed	Children's Hospital of Alabama	Birmingham, 35233, United States
Completed	Children's Healthcare of Atlanta	Atlanta, 30322, United States
Completed	Riley Hospital For Children	Indianapolis, 46202, United States
Completed	Seattle Children's Hospital	Seattle, 98105, United States
Completed	Children's Hospital of Orange County	Orange, 92868-3974, United States
Completed	Children's National Medical Center	Washington, 20010-2970, United States
Completed	Children's Hospital of Pittsburgh of UPMC	Pittsburgh, 15224, United States
Withdrawn	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago, 60611, United States
Completed	Texas Children's Hospital	Houston, 77030, United States
Withdrawn	University of Minnesota Medical Center	Minneapolis, 55455, United States
Withdrawn	C.S. Mott Children's Hospital	Ann Arbor, 48109, United States
Withdrawn	Children's Hospital of Los Angeles	Los Angeles, 90027-6089, United States
Withdrawn	Memorial Sloan-Kettering Cancer Center	New York, 10065, United States
Withdrawn	University of Texas Southwestern Medical Center	Dallas, 75390, United States
Withdrawn	Cook Children's Medical Center	Fort 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.
Time Frame:
Cycle 1 (28 days)
Dose-limiting Toxicities(DLTs)
Phase 1
Time Frame:
Cycle 1 (28 days)
Number of participants with Treatment-emergent Adverse Events(TEAEs)
Phase 1
Time Frame:
Approximately 13 months
Number of participants with Serious Adverse Events (SAEs)
Phase 1
Time Frame:
Approximately 13 months
Number of participants with Treatment-related Adverse Events (AEs).
Phase 1
Time Frame:
Approximately 13 months
Objective response rate (ORR)
Phase 2:ORR is the primary efficacy variable in neuroblastoma, Ewing sarcoma and rhabdomyosarcoma.
Time Frame:
Up to 31 months
Disease control rate (DCR)
Phase 2:DCR is the primary efficacy variable in osteosarcoma.
Time Frame:
Up to 31 months
Progression-free survival (PFS)
Phase 2: PFS is considered as co-primary (descriptively evaluated) variable in patients with osteosarcoma.
Time Frame:
Up to 31 months

Secondary Outcome

Copanlisib maximum drug concentration (Cmax)
Phase 1.
Time 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
Time 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
Time 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
Time 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).
Time 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.
Time 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).
Time 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
Time 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
Time 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

Additional Information

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