Status:

COMPLETED

A Phase I Study of SB939 in Pediatric Patients With Refractory Solid Tumours and Leukemia

Lead Sponsor:

NCIC Clinical Trials Group

Collaborating Sponsors:

S*BIO

Conditions:

Leukemia

Solid Tumours

Eligibility:

All Genders

12-18 years

Phase:

PHASE1

Brief Summary

This research is being done because SB939 has been shown to shrink tumours in animals and in some people and seems promising, but we are not sure if it can offer better results than standard treatment...

Detailed Description

In Part A of this study, SB939 was given to children with solid tumours. The purpose of Part A of this study is to ind the highest dose of a new drug SB939 that can be giben to children without causin...

Eligibility Criteria

Inclusion

  • Patients in all parts of the study must have histological verification of malignancy at either original diagnosis or relapse.
  • For Part A, patients must have recurrent or refractory solid tumours, lymphoma or CNS tumours (excluding diffuse intrinsic pontine gliomas).
  • For Part B, patients must have recurrent or refractory leukemia.
  • For Part C, patients must have one of the following diagnoses: neuroblastoma, or medulloblastoma / CNS primitive neuroectodermal tumour (PNET).
  • Disease Status
  • Patients with solid tumours must have either measurable or evaluable disease (defined by a positive nuclear scan such as bone scan or metaiodobenzylguanidine (MIBG) scan. For part C only, in the case of neuroblastoma, if a lesion is isolated and /or previously irradiated and stable, a proven positive biopsy will be required to be eligible.
  • Patients with refractory or relapsed leukemia must have greater than 25% blasts in bone marrow (M3 bone marrow); active extramedullary disease may also be present. Patients with leptomeningeal disease are not eligible.
  • Therapeutic Options:
  • The patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
  • Prior Systemic Therapy
  • Patients must have recovered from the acute effects of prior chemotherapy, immunotherapy or radiotherapy prior to study entry as follows:
  • At least 3 weeks from completion of myelosuppressive chemotherapy, biologic agents or other investigational cancer treatment
  • At least 7 days from completion of therapy with a growth factor
  • At least 6 weeks from hematopoietic stem cell rescue following myeloablative therapy
  • Post allogeneic hematopoietic transplant patients are eligible, but must have no evidence of active graft vs. host disease
  • At least 2 weeks from completion of local palliative XRT (small port)
  • At least 3 months must have elapsed if prior total body irradiation, craniospinal XRT or if ≥ 50% radiation of pelvis
  • At least 6 weeks must have elapsed if other substantial bone marrow irradiation
  • At least 6 weeks from prior MIBG therapy Age \> 12 months and ≤ 18 years at the time of study entry. Performance Status: Karnofsky ≥ 60% for patients \> 10 years; Lansky ≥ 50 for patients ≤ 10 years.
  • For Patients with Solid Tumours (Parts A and C):
  • Absolute neutrophil count (ANC) ≥ 1.0 x 10 (power of 9)/L
  • Platelets ≥100 x 10(power of 9)/L
  • Hemoglobin ≥ 80 g/L
  • For Patients with Leukemia (Part B only)
  • No minimum absolute neutrophil count
  • Platelet count ≥ 20 x 10 (power of 9)/L (may receive transfusion)
  • Hemoglobin ≥ 80 g/L (may receive transfusion)
  • serum creatinine ≤ 1. 5 x upper limit of normal for age or
  • measured GFR ≥ 70 mL/min/1.73 m2
  • LVEF by ECHO or MUGA Scan within normal institutional limits
  • QTc ≤ 450 msec
  • AST and ALT ≤ 5.0 x upper limit normal for age
  • bilirubin ≤ 1.5 x upper limit normal for age
  • Additional Criteria For Part C Of The Study
  • Skin toxicity (excluding alopecia) ≤ Grade 1
  • Serum triglycerides (fasting) \< 3.4 mmol/L
  • Negative urine dipstick for protein OR \< 1000 mg protein/24 hour urine collection
  • No evidence of gross hematuria
  • Patient or guardian consent must be obtained on all patients according to local Institutional and/or University Human Experimentation Committee requirements.
  • Patients registered on this trial must be treated and followed at the participating centre.
  • Protocol treatment to begin within five working days of patient registration.

Exclusion

  • Cardiac Exclusions. Patients with a pathologic cardiac arrhythmia requiring active treatment. Patients with a history of arrhythmia must be \> 12 months since last treatment with no recurrence of arrhythmia in the interval.
  • Inability To Take Oral Medication. Patients must be able to take oral medication and have no gastrointestinal abnormalities (e.g. bowel obstruction or previous gastric resection) which would lead to inadequate absorption of SB939.
  • Known HIV, hepatitis B or hepatitis C infections.
  • Current treatment with agents with a known risk of Torsades de Pointes http://torsades.org (list #1).
  • Pre-existing peripheral neuropathy ≥ grade 3.
  • There is no available information regarding human fetal or teratogenic toxicities related to SB939. 13-cis-retinoic acid is known to be teratogenic. Pregnancy tests must be obtained in girls who are post menarchal. Males or females of reproductive potential may not participate unless they have agreed to an effective contraceptive method. Pregnant or breast feeding females will not be entered on this study due to the potential fetal and teratogenic adverse events.

Key Trial Info

Start Date :

October 1 2010

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

January 16 2014

Estimated Enrollment :

12 Patients enrolled

Trial Details

Trial ID

NCT01184274

Start Date

October 1 2010

End Date

January 16 2014

Last Update

August 4 2023

Active Locations (8)

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Page 1 of 2 (8 locations)

1

Alberta Children's Hospital

Calgary, Alberta, Canada, T3B 6A8

2

Stollery Children's Hospital

Edmonton, Alberta, Canada, T6G 2B7

3

Children's and Women's Health Centre of BC Branch

Vancouver, British Columbia, Canada, V6H 3V4

4

CancerCare Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9