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Trial record 1 of 53 for:    3f8
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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03860207
Recruitment Status : Recruiting
First Posted : March 1, 2019
Last Update Posted : November 8, 2019
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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

Condition or disease Intervention/treatment Phase
Neuroblastoma Osteosarcoma Other Solid Tumor Cancers Biological: Humanized 3F8 Bispecific Antibody Other: Blood draw Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This phase I/II trial will assess the toxicity and pharmacokinetics (PK) of the humanized anti-GD2 x anti-CD3 bispecific antibody (hu3F8-BsAb) in phase I and the anti-tumor activity of hu3F8-BsAb in phase II.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 22, 2019
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : February 2022


Arm Intervention/treatment
Experimental: Hu3F8-BsAb
Phase 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.
Biological: Humanized 3F8 Bispecific Antibody
Phase I Hu3F8-BsAb is given IV over ~1-3 hours on Days 1 and 8 for each cycle.Phase II Hu3F8-BsAb is given IV over ~1-3 hours on Days 1 and 8 for each cycle.
Other Name: Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb)

Other: Blood draw
In cycle 1, blood is drawn for PK studies.




Primary Outcome Measures :
  1. maximum tolerated dosage (MTD) Phase I [ Time Frame: Days 1 through 28 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03860207


Contacts
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Contact: Shakeel Modak, MD 212-639-7623 modaks@mskcc.org
Contact: Brian Kushner, MD 212-639-6793

Locations
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United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Shakeel Modak, MD    212-639-7623      
Contact: Brian Kushner, MD    212-639-6793      
Principal Investigator: Shakeel Modak         
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Shakeel Modak, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03860207    
Other Study ID Numbers: 18-034
First Posted: March 1, 2019    Key Record Dates
Last Update Posted: November 8, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Supporting Materials: Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
Humanized 3F8 Bispecific Antibody (Hu3F8-BsAb)
18-034
Additional relevant MeSH terms:
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Neuroblastoma
Osteosarcoma
Neoplasms
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Antibodies
Immunoglobulins
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs