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

NCT ID: NCT01184274

Last Updated: 2023-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-01
• Study Completion Date: 2014-01-16

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 causing very severe side effects that are tolerable.

In Part B of this study, SB939 will be given to children with leukemia. The purpose of Part B, is to see whether the dose that was determined to be the best dose for patients with solid tumours is also the best dose for children with leukemia.

In Part C of this study, SB939 will be given together with 13-cis-retinoic acid. The purpose of Part C, is to see whether the SB939 dose that was determined to be the best dose in Part A is also the best dose when given in combination with 13-cis-retinoic acid.

Conditions

Leukemia; Solid Tumours

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SB939

Group Type: EXPERIMENTAL

SB939

Intervention Type: 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

Interventions

SB939

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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 Criteria

• 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.

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

S*BIO

INDUSTRY

Sponsor Role: collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sylvain Baruchel

Role: STUDY_CHAIR

Hospital for Sick Children, Toronto Ontario Canada

Locations

Alberta Children's Hospital

Calgary, Alberta, Canada

Stollery Children's Hospital

Edmonton, Alberta, Canada

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

Vancouver, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Izaak Walton Killam (IWK) Health Centre

Halifax, Nova Scotia, Canada

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Hospital for Sick Children

Toronto, Ontario, Canada

CHU Sainte-Justine

Montreal, Quebec, Canada

Countries

Canada

References

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.

Reference Type: RESULT

PMID: 23893953 (View on PubMed)

Other Identifiers

I203

Identifier Type: -

Identifier Source: org_study_id