Neoplasms

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Liposarcoma

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Sarcoma

Soft Tissue Sarcoma

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Anti-Infective Agents

Azacitidine

Romidepsin

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oral 5-azacitidine in combination with romidepsin

DOSING REGIMEN(S):

Table 1: Dose Escalation Schedule Dose Level Dose and Schedule a, c 5-Azacitidine (PO) Romidepsin (IV)

Level -1b 100mg daily days 1-14 8mg/m2 days 8 and 15

Level 1 200mg daily days 1-14 8mg/m2 days 8 and 15

Level 2 300mg daily days 1-14 8mg/m2 days 8 and 15

Level 3 300mg daily days 1-21 8mg/m2 days 8 and 15

Level 4d MTD 8mg/m2 days 8, 15, and 22

1. Each cycle will last 28 days.
2. Subjects will be enrolled in Level -1 if the MTD is reached in the subjects enrolled in Level 1.
3. On days when both agents are administered, oral 5-azacitidine should be administered at the start of the romidepsin infusion.
4. Level 4 is optional and decisions whether to initiate this level will be based on discussions between the study investigator and Celgene.

Nilofer Azad, MD

The purpose of this study is to determine whether 5-azacitidine in combination with romidepsin cancer are effective in the treatment of advanced solid tumors.

This is a two part, single-institution, open-label, Phase I dose-escalation study of oral 5-azacitidine in combination with intravenous (IV) romidepsin. Part 1 of the study is a traditional 3 + 3 dose escalation study designed to evaluate the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), safety, pharmacokinetic (PK) profiles, and pharmacodynamic profiles of increasing doses of orally administered 5-azacitidine in combination with a constant dose of IV romidepsin. Part 2 is an expansion cohort study for the preliminary evaluation of efficacy in the treatment of virally mediated cancers and liposarcoma once the MTD has been determined. PK and PD data will also be collected for these subjects.

* Plasma samples will be obtained, prior and during treatment, to assess the methylation status of free tumor DNA circulating in the blood
* Archival tissue will be obtained on all participants for future correlative studies, such as baseline gene expression, methylation patterns.
* Participants with accessible, biopsiable tumors will also undergo pre-treatment and post-treatment (\~cycle 2D1) biopsies for correlative studies in the expansion cohort.

A Trial of Oral 5-azacitidine in Combination With Romidepsin in Advanced Solid Tumors, With an Expansion Cohort in Virally Mediated Cancers and Liposarcoma

Phase I Trial of Oral 5-azacitidine With Romidepsin in Advanced Solid Tumors, With an Expansion Cohort in Virally Mediated Cancers and Liposarcoma

Incidence of adverse events, serious adverse events, and dose-limiting adverse events graded according to NCI CTCAE version 4

MTD defined as the highest dose level at which \< 2 out of 6 patients experienced a DLT.

Clinical responses associated with oral 5-azacitidine and romidepsin treatment in subjects with advanced solid malignancies according to RECIST criteria \[Time Frame: measured every two cycles during study treatment, expected duration ≤1.5 years

Peak plasma concentration (Cmax), area under the concentration versus time curve (AUC) from time 0-infinity, elimination half-life (t1/2), clearance, and volume of distribution (Vd)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Trial of Oral 5-azacitidine in Combination With Romidepsin in Advanced Solid Tumors, With an Expansion Cohort in Virally Mediated Cancers and Liposarcoma	NCT01537744	Solid Tumors Virally Mediate...	oral 5-azacitid...	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
A Trial of Oral 5-azacitidine in Combination With Romidepsin in Advanced Solid Tumors, With an Expansion Cohort in Virally Mediated Cancers and Liposarcoma	NCT01537744	Solid Tumors Virally Mediate...	oral 5-azacitid...	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Spots Global Cancer Trial Database for virally mediated cancers and liposarcoma