Study Stopped
no anticipated benefit over available standard therapies
Safety, Tolerability, Efficacy and Pharmacokinetics of Copanlisib in Pediatric Patients
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
2 other identifiers
interventional
31
1 country
14
Brief Summary
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 Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Apr 2018
Longer than P75 for phase_1
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 19, 2018
CompletedFirst Posted
Study publicly available on registry
March 8, 2018
CompletedStudy Start
First participant enrolled
April 30, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2023
CompletedResults Posted
Study results publicly available
December 4, 2023
CompletedDecember 4, 2023
November 1, 2023
4.8 years
February 19, 2018
September 26, 2023
November 29, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (8)
Phase 1: The Maximum Tolerated Dose (MTD): 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.
Maximum tolerated dose (MTD) for copanlisib was defined as the highest dose level where 6 patients have been treated and ≤ 1 participant experienced a DLT. This endpoint was performed on SAF.
Cycle 1 (28 days)
Phase 1: Number of Subjects With Dose Limiting Toxicity (DLT)
DLT was observed during first cycle of treatment, and assessed as possibly, probably or definitely related to treatment with copanlisib. The DLT observation period for the purposes of dose-escalation was the first cycle of therapy.
Cycle 1 (28 days)
Phase 1: Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
TEAE was defined as any event arising or worsening after start of study drug administration until 30 days after the last dose of the study drug intake (end of safety follow-up). This endpoint was performed on SAF.
After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 145 days.
Phase 1: Number of Subjects With Serious Adverse Events (SAEs)
This endpoint was performed on SAF.
Up to 150 days.
Phase 1: Number of Participants With Treatment-related Adverse Events (AEs).
This endpoint was performed on SAF.
Up to 145 days.
Phase 2: Objective Response Rate (ORR)
ORR was defined separately in each indication, as the number of responders divided by the number of subjects in FAS in the indication.
Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Phase 2: Disease Control Rate (DCR)
The DCR was defined as the number of subjects with disease control divided by the number of subjects in FAS or per protocol set (PPS) in the indication.
Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Phase 2: Progression-free Survival (PFS)
Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Secondary Outcomes (9)
Phase 1: Copanlisib Maximum Drug Concentration (Cmax)
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.
Phase 1: Area Under the Curve (AUC(0-168))
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.
Phase 1: Objective Response Rate (ORR)
Up to 150 days
Phase 2: Duration of Response (DOR)
Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Phase 2: PFS in Each Indication Except for Osteosarcoma
Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
- +4 more secondary outcomes
Study Arms (5)
Dose escalation of BAY806946 in Phase 1
EXPERIMENTALIt 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).
Patients with Neuroblastoma in Phase 2
EXPERIMENTALRecommended Phase 2 dose (RP2D) for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.
Patients with Osteosarcoma in Phase 2
EXPERIMENTALRP2D for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.
Patients with Rhabdomyosarcoma in Phase 2
EXPERIMENTALRP2D for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.
Patients with Ewing sarcoma in Phase 2
EXPERIMENTALRP2D for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.
Interventions
Copanlisib will be dosed on Day 1, Day 8, and Day 15 of every 28-day cycle. Phase 1: 2 or 3 dose cohorts may be evaluated in phase 1 of the study. Phase 2: RP2D for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.
Eligibility Criteria
You may qualify if:
- 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.
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bayerlead
Study Sites (14)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Children's Hospital of Orange County
Orange, California, 92868-3974, United States
The Children's Hospital
Aurora, Colorado, 80045, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010-2970, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322, United States
Riley Hospital For Children
Indianapolis, Indiana, 46202, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Columbia University Medical Center
New York, New York, 10032, United States
Cincinnati Children's Hospital and Medical Center
Cincinnati, Ohio, 45229, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Therapeutic Area Head
- Organization
- Bayer AG
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 19, 2018
First Posted
March 8, 2018
Study Start
April 30, 2018
Primary Completion
February 1, 2023
Study Completion
February 1, 2023
Last Updated
December 4, 2023
Results First Posted
December 4, 2023
Record last verified: 2023-11
Data Sharing
- IPD Sharing
- Will not share
Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.