Description:
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.
Title
- Brief Title: Humanized 3F8 Monoclonal Antibody (Hu3F8) in Patients With High-Risk Neuroblastoma and GD2-Positive Tumors
- Official Title: Phase I Study of Humanized 3F8 Monoclonal Antibody (Hu3F8) in Patients With High-Risk Neuroblastoma and GD2-Positive Tumors
Clinical Trial IDs
- ORG STUDY ID:
11-009
- NCT ID:
NCT01419834
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Humanized 3F8 Monoclonal Antibody (Hu3F8) | | Humanized 3F8 Monoclonal Antibody (Hu3F8) |
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.
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Humanized 3F8 Monoclonal Antibody (Hu3F8) | Experimental | This phase I single arm trial assesses the toxicity of escalating doses of hu3F8. | - Humanized 3F8 Monoclonal Antibody (Hu3F8)
|
Eligibility 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 2 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | maximum tolerated dosage (MTD) |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | 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
| Measure: | pharmacokinetics of hu3F8 |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | To assess activity of hu3F8 against NB and other GD2-positive tumors. |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | 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 |
| Measure: | To quantitate pain during hu3F8 treatment |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Memorial Sloan Kettering Cancer Center |
Trial Keywords
- CNS
- Brain
- MAB 3F8
- Hu3F8
- 11-009
Last Updated
August 25, 2021
