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

Bayer

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Osteosarcoma; Neuroblastoma; Rhabdomyosarcoma; Ewing Sarcoma; Relapsed or Refractory Solid Tumors or Lymphoma in Children

Treatments: Drug: Copanlisib (BAY806946)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03458728

2017-000383-15 (EudraCT Number)

19176

Details and patient eligibility

About

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.

Enrollment: 31 patients

Sex: All

Ages: 6 months to 21 years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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31 participants in 5 patient groups

Dose escalation of BAY806946 in Phase 1

Experimental group

Description:

It 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).

Treatment:

Drug: Copanlisib (BAY806946)

Patients with Neuroblastoma in Phase 2

Experimental group

Description:

Recommended Phase 2 dose (RP2D) for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.

Treatment:

Drug: Copanlisib (BAY806946)

Patients with Osteosarcoma in Phase 2

Experimental group

Description:

RP2D for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.

Treatment:

Drug: Copanlisib (BAY806946)

Patients with Rhabdomyosarcoma in Phase 2

Experimental group

Description:

RP2D for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.

Treatment:

Drug: Copanlisib (BAY806946)

Patients with Ewing sarcoma in Phase 2

Experimental group

Description:

RP2D for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.

Treatment:

Drug: Copanlisib (BAY806946)