BXQ-350 in Children and Young Adults with Recurrent Relapsed Solid Tumors or Recurrent Malignant Brain Tumors or Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)

Why are we doing this research?

The purpose of this study determine the safety and tolerability of the drug BXQ-350 and to establish the maximum tolerated dose that can be taken forward into studies of efficacy.

BXQ-350: A Phase 1 Safety Study of BXQ-350 Administered as a Single Agent by Intravenous Infusion in Children and Young Adults with Recurrent or Relapsed Solid Tumors or Recurrent Malignant Brain Tumors or Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)

Who can participate?

Inclusion Criteria:

  • Diagnosed with one of the following:
    • Newly diagnosed DIPG
    • Recurrent solid tumor cancer, including malignant brain tumors
  • Have measurable or non-measurable disease per RECIST v1.1 criteria for recurrent solid tumors, RRC for newly diagnosed DIPG and recurrent malignant brain tumors, and INRC for recurrent neuroblastomas
  • Have Lansky/Karnofsky Performance Score (Age 3-18 years) of >50 or Eastern Cooperative Oncology Group Performance Status (ECOG PS) (Age > 18) of 0 – 2
  • Have acceptable liver function defined as:
    • Total serum bilirubin ≤ 1.5 × upper limit of normal (ULN) for the study site (in subjectswith known Gilbert Syndrome, total bilirubin ≤ 3 × ULN, with direct bilirubin ≤ 1.5 × ULN)
    • Aspartate Transaminase (AST), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alanine Transaminase (ALT), Serum Glutamic-Pyruvic Transamine (SGPT) ≤ 3 × ULN (if liver metastases are present, then ≤ 5 × ULN is allowed)
    • Serum albumin ≥ 3 g/dL
  • Have acceptable renal function defined as:
    • Serum creatinine ≤ 1.5 × ULN, OR calculated creatinine clearance ≥ 45 mL/min for subjects with creatinine levels above 1.5 mg/dL
  • Have acceptable bone marrow function defined as:
    • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
    • Platelet count ≥ 100,000 cells/mm3
    • Hemoglobin > 9.0 g/dL
  • Have acceptable coagulation parameters defined as:
    • International normalized ratio (INR) ≤ 2 × ULN
    • Activated partial thromboplastin time (aPTT) within normal limits
  • Have a negative serum pregnancy test result at screening (for females of child bearing potential (FCBP); not applicable to subjects who are unable to become pregnant, including those with tubal ligation, bilateral oophorectomy and/or hysterectomy)
  • FCBP and male subjects whose sexual partner(s) are FCBP must agree to abstain from heterosexual activity or use highly effective contraception.

Exclusion Criteria:

  • Have a concurrent malignancy or have had another malignancy within 1 year prior to initiation of screening (with the exception of adequately treated basal or squamous cell carcinoma, melanoma in situ, early-stage prostate cancer (T1a-cN0M0), ductal carcinoma in situ of the breast or cervical carcinoma in situ)
  • Have lymphoma
  • Have Grade I ependymoma
  • Have symptomatic brain metastases or leptomeningeal disease
  • Recurrent solid tumors: have received
    • anticancer therapies within 2 weeks prior to dose assignment (including radiation therapy, cytotoxic agents, targeted agents or endocrine therapy)
    • myelosuppressive agents within 3 weeks prior to dose assignment
    • monoclonal antibodies within 4 weeks prior to dose assignment
    • other immunotherapy (tumor vaccine, cytokines or growth factor) within 2 weeks of dose assignment
  • Recurrent malignant brain tumors: have received:
    • anticancer therapies including:
      • radiation therapy to current site of disease within 3 weeks dose assignment
      • targeted agent therapy within 2 weeks of dose assignment
      • nitrosoureas within 6 weeks of dose assignment
      • procarbazine within 3 weeks of dose assignment
      • other cytotoxic agents within 4 weeks of dose assignment
    • myelosuppressive agents within 4 weeks prior to dose assignment
    • monoclonal antibodies within 4 weeks prior to dose assignment
    • other immunotherapy (tumor vaccine, cytokines, or growth factor) within 2 weeks prior to dose assignment
  • Have not recovered from toxicity of prior therapy defined as a return to < grade 1 at the time of dose assignment, graded according to CTCAE v5.0 (excluding alopecia, neuropathy, and lymphopenia)
  • Have had major surgery other than a minor outpatient procedure within 28 days prior to dose assignment or have not recovered from major side effects of the surgery if more than 4 weeks have elapsed since surgery
  • Have poorly controlled hypertension defined as blood pressure >160/90 on at least 2 repeated determinations on separate days within 2 weeks (14 days) prior to initiation of screening
  • Have a history of cardiac dysfunction including any of the following:
    • Myocardial infarction within 6 months prior to initiation of screening
    • History of documented congestive heart failure (within 6 months prior to initiation of screening
    • Active cardiomyopathy
    • Electrocardiogram (ECG) with QTc >480 msec at screening
  • Have a known history of Human Immunodeficiency Virus (HIV) seropositivity
  • Have active (acute or chronic) or uncontrolled severe infections
  • Have active poor wound healing (delayed healing, wound infection or fistula)
  • Have evidence of active clinically significant bleed (e.g., gastrointestinal bleed, hemoptysis,or gross hematuria) at initiation of screening
  • Are pregnant or nursing (lactating), where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum human chorionic gonadotropin (hCG) laboratory test
  • Have received prior treatment with any investigational drug within 28 days prior to dose assignment
  • Have other concurrent severe and/or uncontrolled medical condition that would, in the site Investigator’s judgment contraindicate the subject’s participation in the clinical study

Ages

  • 1 to 30 years

Conditions

  • Adult - Brain Spinal Tumor DIPG New Diagnosis
  • Brain Spinal Tumor DIPG New Diagnosis
  • Brain and Spinal Tumor Ependymoma Relapse
  • Adult - Brain and Spinal Tumor Ependymoma Relapse
  • Brain Spinal Tumors Medulloblastoma Relapse
  • Adult - Brain Spinal Tumors Medulloblastoma Relapse
  • Brain Spinal Tumor Low Grade Glioma Relapse
  • Adult - Brain Spinal Tumor Low Grade Glioma Relapse
  • Brain Spinal Neurofibromatosis Sarcoma MPNST Relapse
  • Adult - Brain Spinal Neurofibromatosis Sarcoma MPNST Relapse
  • Sarcoma Osteosarcoma Relapse
  • Adult - Sarcoma Osteosarcoma Relapse
  • Sarcoma Ewing Relapse
  • Adult - Sarcoma Ewing 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

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