A Phase I Dose Escalation Study of Oral SB939 Administered Alone or With Azacitidine

Study Overview
=================
Brief Summary
-----------------
This is an open label, dose escalation study with 3 arms (Arms A, B, and C). Arm A will assess the safety and tolerability of escalating doses of SB939 in cohorts of patients with advanced solid tumors. Arm B will assess the safety and tolerability of escalating doses in cohorts of patients with advanced hematologic malignancies. Arm C will assess the safety and tolerability of SB939 in combination with standard azacitidine therapy.

Official Title
-----------------
A Phase I Dose Escalation Study of Oral SB939 When Administered Thrice Weekly (Every Other Day) for 3 Weeks in a 4-week Cycle in Patients With Advanced Malignancies

Conditions
-----------------
Solid Tumors, Hematologic Malignancies, Myelodysplastic Syndrome

Intervention / Treatment
-----------------
* Drug: SB939
* Drug: Azacitidine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Arms A & B: Patients with solid tumors in Arm A and hematologic malignancies in Arm B that is classified as intermediate 1 or greater according to the International Prognostic Scoring System (IPSS) risk category for whom therapy is indicated; ECOG performance status (PS) 0-2; Patients must have adequate non-hematologic organ system function. Arm C: Patients with MDS that is classified as intermediate 1 or greater according to the International Prognostic Scoring System (IPSS) risk category for whom therapy is indicated; Have not been treated with azacitidine and are a candidate for treatment with azacitidine; ECOG performance status (PS) 0-2; Patients must have adequate non-hematologic organ system function.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Advanced solid tumors | Drug: SB939<br>* SB939 taken orally in a 4-week cycle.<br>|
| Experimental: B<br>Advanced hematologic malignancies | Drug: SB939<br>* SB939 taken orally in a 4-week cycle.<br>|
| Experimental: C<br>Myelodysplastic Syndrome | Drug: SB939<br>* SB939 taken orally in a 4-week cycle.<br>Drug: Azacitidine<br>* Azacitidine taken orally with SB939 in a 4-week cycle<br>* Other names: Vidaza;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of SB939, administered orally every other day 3 times a week for 3 consecutive weeks, repeated every 4 weeks, either alone (Arms A and B), or in combination with azacitidine therapy in (Arm C). |  | Throughout the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To establish the maximum tolerated dose and a recommended phase II dose of SB939 as a single agent when administered every other day 3 times a week for 3 consecutive weeks, repeated every 4 weeks |  | Throughout the study | 
| To determine the dose limiting toxicities of SB939 |  | Throughout the study | 
| To determine the pharmacokinetic profile of SB939 |  | Throughout the study | 
| To assess histone acetylation in PBMC and other biomarkers |  | Throughout the study | 
| To document anti-tumor activity |  | Throughout the study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SB939, Myelodysplastic Syndrome, Combination with azacitidine, Solid malignancies, Hematologic malignancies, HDAC inhibitor, Refractory to standard therapy