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

Sponsor:	Memorial Sloan-Kettering Cancer Center
Information provided by (Responsible Party):	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT01419834

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.

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

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized 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:

MedlinePlus related topics: Cancer Neuroblastoma

U.S. FDA Resources

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 first two iv doses of hu3F8. Serum hu3F8 will be measured at time 0, 5 min, 3h, 6-8h, 24h, 48h, 72h, 96, 120h and 168h after infusion for each of the two hu3F8 injections during the first cycle. Peak hu3F8 level 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:	72
Study Start Date:	August 2011
Estimated Study Completion Date:	August 2013
Estimated Primary Completion Date:	August 2013 (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) One cycle has 2 days of intravenous hu3F8 treatment, given approximately 7 days apart. 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. Evaluations before, during and after treatment are summarized in table 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.

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)

One cycle has 2 days of intravenous hu3F8 treatment, given approximately 7 days apart. 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. Evaluations before, during and after treatment are summarized in table 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:	1 Year to 21 Years
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 metastatic tumor that is GD2-positive by immunostaining with m3F8.
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 between 1 year and less than 22 years 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 > or = to 25,000/ul
Patient taking antihypertensive medication.
Active life-threatening infection.
Pregnant women or women who are breast-feeding.
Inability to comply with protocol requirements.

Contacts and Locations

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

Contacts

Contact: Ellen Basu, MD, PhD	212-639-5204
Contact: Nai-Kong Cheung, MD, PhD	646-888-2313

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: Nai-Kong Cheung, MD, PhD 646-888-2313
Principal Investigator: Ellen Basu, MD, PhD

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Investigators

Principal Investigator:

Ellen Basu, MD,PhD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

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:	March 7, 2012
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
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms

Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2012