Humanized 3F8 Monoclonal Antibody (Hu3F8) in Patients With High-Risk Neuroblastoma and GD2-Positive Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by Memorial Sloan Kettering Cancer Center
Sponsor:
Collaborators:
United States Department of Defense
Band of Parents
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01419834
First received: August 17, 2011
Last updated: February 15, 2016
Last verified: February 2016
  Purpose

The purpose of this study is to find out if "humanized 3F8" (Hu3F8) is safe for treating neuroblastoma and other cancers. A phase 1 study means the investigators are trying to find out what side effects happen when higher and higher doses of a drug are used.

The investigators want to find out what effects, good and/or bad, Hu3F8 has on cancer. The amount of Hu3F8 that patients gets will depend on when they start treatment on this study. The investigators also want to find out more about how Hu3F8 works and how effective it is in attacking the disease. Hu3F8 is an experimental drug, which means it has not yet been approved by the FDA for the treatment of this disease.


Condition Intervention Phase
Neuroblastoma
Biological: Humanized 3F8 Monoclonal Antibody (Hu3F8)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Humanized 3F8 Monoclonal Antibody (Hu3F8) in Patients With High-Risk Neuroblastoma and GD2-Positive Tumors

Resource links provided by NLM:


Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:
  • maximum tolerated dosage (MTD) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    At least 3 patients will be studied at each dosage level and dose escalations will only be carried out if 0/3 or < or = to 1/6 patients have dose-limiting toxicity (DLT). At least six patients will be studied at the maximum tolerated dosage (MTD).


Secondary Outcome Measures:
  • pharmacokinetics of hu3F8 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Pharmacokinetics will be measured by serial blood sampling following the iv doses of hu3F8 during cycle 1. Serum hu3F8 will be measured at the following times after infusion of the first hu3F8 infusion during the first cycle: 0, 5 min, 3h, 6-8h, 24h, 48h, 72h, 96, 120h 168h, 216h and 264 h and will also include peak hu3F8 level after infusion for each of the two hu3F8 injections during the first cycle. Peak hu3F8 level at 5 minutes after hu3F8 infusion on days 3 and 5. Pre-treatment and at 5 min after infusion will also be measured for all hu3F8 infusions during all other cycles.

  • To assess activity of hu3F8 against NB and other GD2-positive tumors. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    For neuroblastoma, anti-tumor activity will be measured by INRC.61 For other solid tumors, the response and progression will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) Committee, version 1.1.62

  • To quantitate pain during hu3F8 treatment [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    As patient's pain will be assessed with a numerical score of 1 to 10 over the course of the treatment, a curve of pain intensity over time can be generated for each patient.


Estimated Enrollment: 74
Study Start Date: August 2011
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Humanized 3F8 Monoclonal Antibody (Hu3F8)
This phase I single arm trial assesses the toxicity of escalating doses of hu3F8.
Biological: Humanized 3F8 Monoclonal Antibody (Hu3F8)
Hu3F8 is infused IV over ~30 minutes

Detailed Description:

Patients can be treated on 2 different schedules:

For patients following a 2 doses/cycle schedule (patients who were enrolled and started treatment prior to Amendment A(8)), one cycle has 2 days of intravenous hu3F8 treatment, given approximately 7 days apart.

For patients following a 3 doses/cycle schedule, one cycle has 3 days of intravenous hu3F8 treatment, given on days 1, 3 and 5. After Cycle 1, patients may receive treatment on a modified schedule of 3 days of intravenous hu3F8 over 10 days, as needed. To limit side-effects, patients receive analgesics and antihistamines as premedications. Cycles are 21 days and can be repeated up to a total of 12 cycles, see section 9.1 for details. Evaluations before, during and after treatment are summarized in Tables 4A and B. In addition, to further study the side effect of pain, patients will be asked to assess their pain on the days of treatment with hu3F8 at 3 different time points: (a) prior to commencement of hu3F8, (b) at least once during the acute pain episode when rescue pain medication doses are usually required and (c) prior to discharge from the Pediatric Day Hospital.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have either (1) a diagnosis of NB as defined by international criteria,56 i.e., histopathology (confirmed by the MSKCC Department of Pathology) or BM metastases plus high urine catecholamine levels, or (2) a tumor that is GD2-positive by immunostaining with m3F8.

    °A non-NB tumor is defined as GD2-positive by immunostaining with m3F8. If fresh or frozen tumor is not available for immunostaining, patients will be considered eligible if published reports show that >50% of that tumor type is GD2-positive by immunohistochemistry. (Note: Tissues must be fresh/frozen as fixed, paraffin-embedded specimens are unsuitable for anti-GD2 immunostaining). Tumors known to be GD2-positive by this criteria do not need immunostaining. These include: Melanoma (>50%), Desmoplastic small round cell tumors (70%), Osteosarcoma (88%) and Soft tissue sarcomas including liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and spindle cell sarcoma (93%).

  • Patients must have either (1) refractory or relapsed high-risk NB (including MYCN-amplified stage 3/4/4S and MYCN-nonamplified stage 4 in patients greater than 18 months of age) resistant to standard therapy, or (2) refractory or relapsed GD2-positive tumor.
  • Patients must be older than 1 year of age.
  • Prior treatment with murine 3F8 is allowed. Patients with prior m3F8 or ch14.18 treatment must have HAHA antibody titer less than the upper limit of normal [defined as mean + 3*SD of normal volunteers].
  • Negative serum pregnancy test in women of childbearing 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:

  • Existing major organ dysfunction > grade 2, with the exception of hearing loss and myelosuppression defined as suppression of all types of WBCs, RBCs and platelets). However, the following parameters must be met: white blood cell count ≥1000/ul, absolute (neutrophil count ≥500/ul absolute lymphocyte count ≥500/ul and platelet count ≥ to 25,000/ul
  • Active life-threatening infection.
  • Pregnant women or women who are breast-feeding.
  • Inability to comply with protocol requirements.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01419834

Contacts
Contact: Ellen Basu, MD, PhD 212-639-5204
Contact: Brian Kushner, MD 212-639-6793

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Ellen Basu, MD, PhD    212-639-5204      
Contact: Brian Kushner, MD    212-639-6793      
Principal Investigator: Ellen Basu, MD, PhD         
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
United States Department of Defense
Band of Parents
Investigators
Principal Investigator: Ellen Basu, MD,PhD Memorial Sloan Kettering Cancer Center
  More Information

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01419834     History of Changes
Other Study ID Numbers: 11-009 
Study First Received: August 17, 2011
Last Updated: February 15, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan Kettering Cancer Center:
CNS
Brain
MAB 3F8
Hu3F8
11-009

Additional relevant MeSH terms:
Neuroblastoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Antibodies
Antibodies, Monoclonal
Immunoglobulins
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 04, 2016