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Study of the Safety and Efficacy of Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb) in Patients With Relapsed/Refractory Neuroblastoma, Osteosarcoma and Other Solid Tumor Cancers

NCT03860207

Description:

The purpose of this study is to test the safety of a study drug called humanized 3F8 bispecific antibody (Hu3F8-BsAb).

Related Conditions:
  • Desmoplastic Small Round Cell Tumor
  • Fibrosarcoma
  • Leiomyosarcoma
  • Liposarcoma
  • Medulloblastoma
  • Melanoma
  • Neuroblastoma
  • Osteosarcoma
  • Retinoblastoma
  • Soft Tissue Sarcoma
  • Spindle Cell Sarcoma
  • Undifferentiated Pleomorphic Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of the Safety and Efficacy of Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb) in Patients With Relapsed/Refractory Neuroblastoma, Osteosarcoma and Other Solid Tumor Cancers
  • Official Title: Phase I/II Study of Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb) in Patients With Relapsed/Refractory Neuroblastoma, Osteosarcoma, and Other GD2(+) Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 18-034
  • NCT ID: NCT03860207

Conditions

  • Neuroblastoma
  • Osteosarcoma
  • Other Solid Tumor Cancers

Interventions

DrugSynonymsArms
Humanized 3F8 Bispecific AntibodyHumanized 3F8 Bispecific Antibody (Hu3F8-BsAb)Hu3F8-BsAb

Purpose

The purpose of this study is to test the safety of a study drug called humanized 3F8 bispecific antibody (Hu3F8-BsAb).

Trial Arms

NameTypeDescriptionInterventions
Hu3F8-BsAbExperimentalPhase I Hu3F8-BsAb is given IV over ~1-3 hours on Days 1 and 8 for each cycle. In cycle 1, blood is drawn for PK studies.Phase II Hu3F8-BsAb is given IV over ~1-3 hours on Days 1 and 8 for each cycle.
  • Humanized 3F8 Bispecific Antibody

Eligibility Criteria

        Inclusion Criteria:

        Phase I

          -  Patients must have either (1) a diagnosis of NB as defined by international
             criteria,i.e.,histopathology (confirmed by the MSKCC Department of Pathology) or BM
             metastases plus high urine catecholamine levels, or (2) high grade osteosarcoma
             verified by histopathology (confirmed by the MSKCC Department of Pathology), or (3)
             other GD2-expressing solid tumor.

          -  For tumors other than NB and osteosarcoma, only tumors known to be GD2 positive are
             eligible: melanoma, desmoplastic small round cell tumors, retinoblastoma,
             medulloblastoma, and soft tissue sarcomas including liposarcoma, fibrosarcoma,
             malignant fibrous histiocytoma, leiomyosarcoma, and spindle cell sarcoma. Patients
             with medulloblastoma are eligible only if they have metastatic disease outside the CNS
             (e.g. in the bone marrow)

          -  NB patients must have chemorefractory (e.g. refractory to standard induction
             chemotherapy including cyclophosphamide, vincristine, cisplatin, etoposide) or
             relapsed high-risk (HR) neuroblastoma. HR NB is defined as MYCN-amplified stage 3/4/4S
             of any age, or MYCNnonamplified stage 4 in patients > 18 months of age at diagnosis.

          -  Osteosarcoma patients must have relapsed or refractory osteosarcoma after receiving
             standard systemic chemotherapy (e.g. combination methotrexate, doxorubicin, and
             cisplatin [MAP]).

          -  For non-NB and non-osteosarcoma tumors known to be GD2(+), patients must have relapsed
             or refractory disease that is resistant to standard therapy.

        Phase II

        Group 1:

          -  NB patients must have chemo refractory or relapsed HR NB. HR NB is defined as
             MYCNamplified stage 3/4/4S of any age, or MYCN-nonamplified stage 4 in patients > 18
             months of age at diagnosis.

          -  The diagnosis of NB must be defined by international criteria i.e., histopathology
             (confirmed by the MSKCC Department of Pathology) or BM metastases plus high urine
             catecholamine levels.

        Group 2:

          -  Patients must have a diagnosis of high grade osteosarcoma defined by histopathology
             (confirmed by the MSKCC Department of Pathology).

          -  Patients must have relapsed or refractory osteosarcoma after receiving standard
             systemic chemotherapy (e.g. combination methotrexate, doxorubicin, and cisplatin
             [MAP]).

        All criteria below are common to both phase I and phase II:

        Disease status

          -  For NB patients, patients must have measurable or evaluable disease (e.g. abnormal
             findings in computed tomography (CT), magnetic resonance imaging (MRI),
             metaiodobenzylguanidine (MIBG) scan, or positron emission tomography (PET)) OR
             morphologic evidence of disease in bone marrow.

          -  For osteosarcoma or other GD2(+) solid tumor patients, patients must have measurable
             disease.

        Other criteria:

          -  Patients must be ≥ 1 year of age.

          -  Patients with prior exposure to anti-GD2 antibodies must have HAHA titer <1300U/ml.

          -  Adequate hematopoietic function defined as:

               -  Absolute neutrophil count ≥500/ul

               -  Absolute lymphocyte count ≥500/ul

               -  Platelet count ≥25,000/ul

          -  Negative serum pregnancy test in women of child-bearing potential.

          -  Women of child-bearing potential must be willing to practice an effective method of
             birth control while on treatment.

          -  Signed informed consent indicating awareness of the investigational nature of this
             program.

        Exclusion Criteria:

          -  Patients who are in complete remission.

          -  Existing severe major organ dysfunction. i.e. renal, cardiac, hepatic, neurologic,
             pulmonary, or gastrointestinal toxicity ≥ Grade 3 except for hearing loss, alopecia,
             anorexia, nausea, hyperbilirubinemia or hypomagnesemia from TPN, which may be Grade 3.

          -  Hematologic and active CNS malignancies including CNS metastasis.

          -  Active life-threatening infection.

          -  Pregnant women or women who are breast-feeding.

          -  Inability to comply with protocol requirements.

          -  History of autoimmune disease with potential CNS involvement or a current autoimmune
             disease.

          -  Chemotherapy or immunotherapy within three weeks prior to study enrollment. T-cell
             based immunotherapies (e.g. CAR-modified T cells, checkpoint inhibitors) should have
             been completed >6 weeks prior to treatment with hu3F8-BsAb.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:maximum tolerated dosage (MTD) Phase I
Time Frame:Days 1 through 28
Safety Issue:
Description:The MTD will be defined as the dose whose toxicity rate does not exceed an acceptable threshold of toxicity of 15%.Toxicity will be monitored using CTCAE version 4.0. DLT only during cycle 1, i.e. Days 1 through 28. Allowance will be made for the expected toxicities of hu3F8 from which hu3F8-BsAb was derived.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb)
  • 18-034

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