Clinical trial NCT01598454: Use of Racotumomab in Patients With Pediatric Tumors Expressing N-glycolylated Gangliosides
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neuroblastoma
Ewing's Sarcoma
Wilm's Tumor
Retinoblastoma
Glioma
Lead sponsor: Laboratorio Elea Phoenix S.A.
Sponsor class: INDUSTRY
Collaborators: name: Ministerio de Ciencia e Innovación, Spain
First posted: 2012-05-15
Enrollment: 15
Sex: ALL
Minimum age (years): 1
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Selection of the higher safe dose level for ensuing clinical trials
timeFrame: Up to 1 year
Secondary outcomes:
measure: Assess the immune response to racotumomab treatment
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Prof. Dr. J. P. Garrahan National Children's Hospital
Study officials:
affiliation: Prof. Dr. J. P. Garrahan National Children's Hospital
name: Walter Cacciavillano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Prof. Dr. J. P. Garrahan National Children's Hospital
name: Guillermo Chantada, MD
role: STUDY_DIRECTOR
References:
citation: Cacciavillano W, Sampor C, Venier C, Gabri MR, de Davila MT, Galluzzo ML, Guthmann MD, Fainboim L, Alonso DF, Chantada GL. A Phase I Study of the Anti-Idiotype Vaccine Racotumomab in Neuroblastoma and Other Pediatric Refractory Malignancies. Pediatr Blood Cancer. 2015 Dec;62(12):2120-4. doi: 10.1002/pbc.25631. Epub 2015 Jul 7.