ADVL1721: 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

Why are we doing this research?

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.


PRIMARY OUTCOME MEASURES:

  • The maximum tolerated dose (MTD) [ Time Frame: Approximately 8 months ]
    • 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.
  • Dose-limiting Toxicities(DLTs) [ Time Frame: Approximately 8 months ]
    • Phase 1
  • Number of participants with Treatment-emergent Adverse Events(TEAEs) [ Time Frame: Approximately 13 months ]
    • Phase 1
  • Number of participants with Serious Adverse Events (SAEs) [ Time Frame: Approximately 13 months ]
    • Phase 1
  • Number of participants with Treatment-related Adverse Events (AEs). [ Time Frame: Approximately 13 months ]
    • Phase 1
  • Objective response rate (ORR) [ Time Frame: Up to 31 months ]
    • Phase 2: ORR is the primary efficacy variable in neuroblastoma, Ewing sarcoma and rhabdomyosarcoma.
  • Disease control rate (DCR) [ Time Frame: Up to 31 months ]
    • Phase 2: DCR is the primary efficacy variable in osteosarcoma.
  • Progression-free survival (PFS) [ Time Frame: Up to 31 months ]
    • Phase 2: PFS is considered as co-primary (descriptively evaluated) variable in patients with osteosarcoma..

Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Parallel Assignment

Masking: None (Open Label)

Primary Purpose: Treatment

Who can participate?

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 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 or evaluable (for neuroblastoma and Ewing sarcoma) disease. 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.

Ages

  • 6 months to 21 Years

Conditions

  • Lymphoma Hodgkin Relapse
  • Lymphoma Non Hodgkin Relapse
  • Adult - Lymphoma Non Hodgkin Relapse
  • Adult - Lymphoma Hodgkin Relapse
  • Sarcoma Osteosarcoma Relapse
  • Adult - Sarcoma Osteosarcoma Relapse
  • Sarcoma Rhabdomyosarcoma Relapse
  • Adult - Sarcoma Rhabdomyosarcoma Relapse
  • Neuroblastoma Relapse - Refractory
  • Adult - Neuroblastoma Relapse - Refractory
  • Liver Relapse - Refractory
  • Adult - Liver Relapse - Refractory
  • Kidney Relapse - Refractory
  • Adult - Kidney Relapse - Refractory
  • Solid Tumor Retinoblastoma Relapse - Refractory
  • Adult - Solid Tumor Retinoblastoma Relapse - Refractory
  • Solid Tumor Neurofibromatosis Sarcoma MPNST Relapse - Refractory
  • Adult - Solid Tumor Neurofibromatosis Sarcoma MPNST Relapse - Refractory
  • Adult - Solid Tumor Neurofibromatosis OPG Low Grade Glioma
  • Solid Tumor Neurofibromatosis OPG Low Grade Glioma
  • Adult - Solid Tumor Neurofibromatosis Other
  • Solid Tumor Neurofibromatosis Other
  • Solid Tumor Melanoma Relapse - Refractory
  • Adult - Solid Tumor Melanoma Relapse - Refractory
  • Solid Tumor Germ Cell Tumor Relapse - Refractory
  • Adult - Solid Tumor Germ Cell Tumor Relapse - Refractory
  • Solid Tumors - All Other
  • Adult - Solid Tumors - All Other

Contact

Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039
Phone: 513-636-2799
cancer@cchmc.org