Use of Racotumomab in Patients With Pediatric Tumors Expressing N-glycolylated Gangliosides

Study Overview
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Brief Summary
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This study will be carried out in children with diagnosis of cancer with tumors known to express N-glycolylated gangliosides. The disease must be resistant to conventional therapy. The acute toxicity and immune response will be evaluated. The expression of N-glycolylated gangliosides in tumors has previously been investigated in the tumor sample bank at this Hospital. The expression of N-glycolyl GM3 was shown in neuroblastoma, Ewing's sarcoma, Wilm's tumor and retinoblastoma. Gliomas and the aforementioned tumor types have a very bad prognosis when conventional treatment is ineffective. New therapeutic strategies have thus been examined, and several immunotherapeutic approaches, including dendritic cell vaccines, peptide vaccines and anti-idiotype vaccines are currently being assessed. Racotumomab is an anti-idiotype antibody capable of inducing anti-N-glycolyl GM3 antibodies in patients with melanoma, breast cancer and lung cancer. Dose escalation studies have shown the safety of racotumomab in the 0.5 to 2 mg dose range. The 1 mg dose level was selected for the ensuing clinical studies. This clinical trial in children involves three dose levels: 0.15 mg, 0.25 mg and 0.4 mg, owing to the difference in body surface between an adult (1.73 sq. m in average) and the candidate population for this study (0.55 to 0.7 sq. m).

Official Title
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Phase 1 Study on the Use of Racotumomab Anti-idiotype Antibody in Patients With Pediatric Malignancies That Express N-glycolylated Gangliosides and Are Resistant to Conventional Treatment.

Conditions
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Neuroblastoma, Ewing's Sarcoma, Wilm's Tumor, Retinoblastoma, Glioma

Intervention / Treatment
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* Drug: racotumomab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children (both genders) of between 1 and 10 years old at the time of accrual. Diagnosis of neuroblastoma (progression after first line treatment), glioma (progressing disease or metastatic disease, without curative treatment options), Ewing's sarcoma (progressive metastatic disease to first line treatment or progressive disease to second line treatment), Wilm's tumor (metastatic relapse after treatment), or retinoblastoma (progressing disease or metastatic relapse during or after first line treatment). Previous cancer treatment finished 30 days before accrual. Lansky performance status over 50. Exclusion Criteria: History of encephalopathy, convulsions, asthma or severe allergy. Infectious disease grade 3 or 4 according to CTCAE version 3. Hepatic, kidney or cardiac insufficiency. Marrow insufficiency after self-transplantation of hematopoietic stem cells. Weight inferior to 12 kg at the time of accrual. Concomitant cancer treatment. Inability to comply with study procedures.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Racotumomab<br> | Drug: racotumomab<br>* Dosage form: intradermal injection. Dosage: 0.15 mg; 0.25 mg; 0.4 mg. Frequency: 3 biweekly injections or 6 biweekly injections. Duration: 4 weeks or 10 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Selection of the higher safe dose level for ensuing clinical trials | One of the three dose levels assessed in this study will be selected for further clinical testing in children: 0.15 mg, 0,25 mg or 0.4 mg. | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the immune response to racotumomab treatment | Active specific immunotherapy with racotumomab has shown to elicit antigen-specific immune responses in adult patients. The elicitation of anti-immunogen and anti-ganglioside antibodies will be assessed in serum samples prior and after racotumomab treatment. | Up to 1 year |