Neoplasms

All Conditions

Rare Diseases

Liposarcoma

Neoplasms, Adipose Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Azacitidine

Romidepsin

Antimetabolites

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Histone Deacetylase Inhibitors

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)

Celgene Corporation

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Respiratory Tract (Lung and Bronchial) Diseases

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

Vaccines

Poly ICLC

Six patients will be enrolled in the Phase 1 safety cohort. Patients will have an IR guided biopsy and FNA. Up to four core biopsies and FNAs at one site will be performed prior to intratumoral (IT) administration of Poly-ICLC. Pleural fluid will be collected for research analysis if available. Poly-ICLC will be injected in 2 locations within the pleura. Patients will undergo surgery 21±7 days after the biopsy and Poly-ICLC intratumoral (IT) injection. The type of surgery that will be performed is at the discretion of the thoracic surgeon and per the standard of care. This includes pleurectomy/decortication or extrapleural pneumonectomy. Patients will be evaluated per the standard of care post-operatively. On day 7±4 days a final toxicity assessment, physical exam and research blood will be collected. All post-operative care and monitoring thereafter is as per standard of care.

If at most one (1) patient in the Phase 1 safety cohort experiences a DLT then a total of thirteen (13) additional patients will be enrolled into the Phase 1b Expansion Cohort. Patients in the Expansion Cohort will receive the same dose and schedule of Poly-ICLC as in the Phase 1 safety cohort. Patients will be followed for safety and tolerability, as well as efficacy. If a total of 4 or more patients experience DLTs then the study will be closed due to excessive toxicity.

Safety

Expansion Cohort

Director, New York Mesothelioma Program

David Yankelevitz, MD

Andrea Wolf

Thomas Marron, MD

This study will examine the safety and potential effectiveness of poly-ICLC directly injected into malignant pleural mesothelioma at the time of biopsy up to 21 days prior to the cancer being removed by the surgeon

* To evaluate the safety and toxicity of IT Poly-ICLC, Hiltonol® prior to surgical resection for patients with MPM.
* To determine objective response rate by RECIST 1.1 using CT imaging.
* To determine recurrence free survival of subjects treated with IT Poly-ICLC followed by surgical resection defined as the time of injection until the first date that recurrent disease is confirmed or date of documented death.
* To evaluate IT Poly-ICLC induced immune changes in the tumor microenvironment by comparing pre-injection biopsy to surgically resected tissue for immune cell infiltration and T cell receptor (TCR) diversity.
* To characterize additional immune parameters in IT Poly-ICLC injected tumors including in-depth phenotypic and functional characterization of immune infiltrating cells.
* To evaluate IT Poly-ICLC induced serological changes and changes of circulating immune cells, including regulatory T cells and NK cells, by comparing pre-injection to post-surgical resection blood samples.

Study Subjects will receive poly-ICLC once within the pleural mesothelioma. Up to twenty one days later he/she will undergo surgery per the standard of care by the thoracic surgeon. The type of surgery will be decided upon by the treating thoracic surgeon. Follows up visits are scheduled every three months for the first year and then every 6 months thereafter. CT scans or surveillance scans to look for recurrences will be ordered by the treating surgeon and/or medical oncologist per the standard of care. If there is a need for adjuvant (after surgery) therapy, such as chemotherapy or radiation, this will be discussed with the study subject per the standard of care by the surgeon and/or a medical oncologist or radiation oncologist.

Poly-ICLC (Hiltonol®) Vaccine In Malignant Pleural Mesothelioma

Direct Injection of Poly-ICLC (Hiltonol®) Vaccine In Malignant Pleural Mesothelioma

Rebecca Hernandez is the Administrative Assistant for this study and should have access to the PRS for this study.

Contact Information:

email: rebecca.hernandez@mssm.edu Phone: 212-824-9472.

Safety will be assessed by the frequency and severity of toxicities by use of NCI-CTCAE 5.0 criteria.

Local Recurrence-free survival from time of first injection until first date that locally recurrent disease is confirmed or date of documented death.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
Poly-ICLC (Hiltonol®) Vaccine In Malignant Pleural Mesothelioma	NCT04525859	Malignant Pleur...	Safety Expansion Cohor...	-	Oncovir, Inc.
Poly-ICLC (Hiltonol®) Vaccine In Malignant Pleural Mesothelioma	NCT04525859	Malignant Pleur...	Safety Expansion Cohor...	-	Oncovir, Inc.
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 expansion cohort