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

NCT01184274 | Completed Phase 1 DMC

• 1 other identifier: I203
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 8

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.

Conditions

Leukemia; Solid Tumours

Outcome Measures

Primary Outcomes (4)

• Part A: Maximum Tolerated Dose and RP2D in solid tumours

  Part A: patients must have recurrent or refractory solid tumours, lymphoma or CNS tumours (excluding diffuse intrinsic pontine gliomas) Purpose is to determine recommended phase II dose (RP2D) of oral SB939 in pediatric patients with solid tumours, with SB939 administered at a starting dose of 25 mg/m2 (70% of the adult recommended phase II dose), and given orally every other day three times / week (e.g. Monday / Wednesday /Friday OR Tuesday / Thursday / Saturday) for three consecutive weeks, followed by one week off-dosing.

  24 months

• Part B: Tolerability

  Part B: patients must have recurrent or refractory leukemia Tolerability of the solid tumour RP2D in patients with recurrent or refractory leukemia once the RP2D has been established in solid tumours.

  24 months

• Part C: Recommended Phase 2 Dose (RP2D) and Tolerability

  Part C: patients must have neuroblastoma, or medulloblastoma/CNS primitive neuroectodermal tumour (PNET) RP2D of oral SB939 in combination with a fixed dose of 13-cisretinoic acid in children with refractory or recurrent neuroblastoma, medulloblastoma / CNS neuroectodermal tumour (PNET), using the recommended dose determined in Part A of this study.

  24 months

• Pharmacokinetics

  characterize the pharmacokinetics of SB939 in a pediatric population

  24 months

Secondary Outcomes (1)

• Anti-tumour activity

  24 months

Study Arms (1)

SB939

EXPERIMENTAL

Drug: SB939

Interventions

SB939 DRUG

Dose Levels for Part A -1 - 20mg/m2 - oral - Every other day three times/week1 for three consecutive weeks, followed by one week off-dosing 1. (starting dose) 25mg/m2 - oral - Every other day three times/week1 for three consecutive weeks, followed by one week off-dosing 2. \- 35mg/m2 - oral - Every other day three times/week1 for three consecutive weeks, followed by one week off-dosing 3. \- 45mg/m2 - oral - Every other day three times/week1 for three consecutive weeks, followed by one week off-dosing 4+ - Previous level + 10mg/m2 - oral - Every other day three times/week1 for three consecutive weeks, followed by one week off-dosing

SB939

Eligibility Criteria

• Age: 12 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• S*BIO: collaborator

Study Sites (8)

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

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

Vancouver, British Columbia, V6H 3V4, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Izaak Walton Killam (IWK) Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (1)

• Zorzi AP, Bernstein M, Samson Y, Wall DA, Desai S, Nicksy D, Wainman N, Eisenhauer E, Baruchel S. A phase I study of histone deacetylase inhibitor, pracinostat (SB939), in pediatric patients with refractory solid tumors: IND203 a trial of the NCIC IND program/C17 pediatric phase I consortium. Pediatr Blood Cancer. 2013 Nov;60(11):1868-74. doi: 10.1002/pbc.24694. Epub 2013 Jul 25.

  PMID: 23893953 RESULT

MeSH Terms

Conditions

Leukemia

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Sylvain Baruchel

  Hospital for Sick Children, Toronto Ontario Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2010
• First Posted: August 18, 2010
• Study Start: October 1, 2010
• Primary Completion: April 12, 2012
• Study Completion: January 16, 2014
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (8)