Clinical trial NCT03458728: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Relapsed or Refractory Solid Tumors or Lymphoma in Children
Neuroblastoma
Osteosarcoma
Rhabdomyosarcoma
Ewing Sarcoma
Keywords: Phase I: relapsed or refractory solid tumors or lymphoma
Phase II: relapsed or refractory solid tumors (neuroblastoma, osteosarcoma, rhabdomyosarcoma or Ewing sarcoma)
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2018-03-08
Enrollment: 31
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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, 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.

Primary outcomes:
measure: 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.
timeFrame: Cycle 1 (28 days)
measure: Phase 1: Number of Subjects With Dose Limiting Toxicity (DLT)
timeFrame: Cycle 1 (28 days)
measure: Phase 1: Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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.
measure: Phase 1: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Up to 150 days.
measure: Phase 1: Number of Participants With Treatment-related Adverse Events (AEs).
timeFrame: Up to 145 days.
measure: Phase 2: Objective Response Rate (ORR)
timeFrame: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
measure: Phase 2: Disease Control Rate (DCR)
timeFrame: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
measure: Phase 2: Progression-free Survival (PFS)
timeFrame: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Secondary outcomes:
measure: Phase 1: Copanlisib Maximum Drug Concentration (Cmax)
timeFrame: 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.
measure: Phase 1: Area Under the Curve (AUC(0-168))
timeFrame: 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.
measure: Phase 1: Objective Response Rate (ORR)
timeFrame: Up to 150 days
measure: Phase 2: Duration of Response (DOR)
timeFrame: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
measure: Phase 2: PFS in Each Indication Except for Osteosarcoma
timeFrame: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
measure: Phase 2: Overall Survival (OS)
timeFrame: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
measure: Phase 2: Number of Participants With Treatment-emergent AEs
timeFrame: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
measure: Phase 2: Number of Subjects With Treatment Emergent SAEs
timeFrame: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
measure: Phase 2: Number of Subjects With Treatment-emergent Clinically Significant Change in Laboratory Parameters, ECGs and Vital Signs
timeFrame: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Aurora
country: United States
facility: The Children's Hospital
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Indianapolis
country: United States
facility: Riley Hospital For Children
state: Indiana
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital and Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
References: