OBP-801

This Phase 1a, single center, open-label, repeat dose study will evaluate the safety, efficacy, and Pharmacokinetics of ascending doses of OBP-801 in patients with advanced solid tumors.

A Dose-Escalation Study of OBP-801 in Patients With Advanced Solid Tumors

A Phase 1a Dose-Escalation Study of OBP-801 in Patients With Advanced Solid Tumors

Oncolys BioPharma Inc

Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Anticonvulsants

Central Nervous System Depressants

Psychotropic Drugs

All Drugs and Chemicals

Valproic Acid

Enzyme Inhibitors

Neurotransmitter Agents

Valproic acid will be orally administered in a total dose of 1500mg per day (500mg, every 8 hours), for three months.

Placebo will be orally administered in a total dose of three capsules per day (every 8 hours), for three months.

Half of the participants will receive valproic acid orally for three months. Saliva and blood will be sampled in the study entry. The participants will be followed with blood tests every month for three cycles. After the third cycle, saliva and blood will be sampled once more. Finally, histone acetylation and DNMT expression will be studied comparing the samples collected in different timelines and comparing them to saliva collected in placebo arm.

The other half of the participants will receive placebo for three months. Saliva and blood will be sampled in the study entry. The participants will be followed with blood tests every month for three cycles. After the third cycle, saliva and blood will be sampled once more. Finally, histone acetylation and DNMT expression will be studied comparing the samples collected in different timelines and comparing them to saliva collected in valproic acid arm.

Placebo

Ricardo Gama, MD, PHD

André Lopes Carvalho, MD, PHD

Luciano de Souza Viana, MD, PHD

This study evaluates the addition of valproic acid as a chemopreventive drug in head and neck squamous cell carcinoma (HNSCC) patients that do not have signs of recurrence or residual disease. The participants will be randomized 1:1 (valproic acid : placebo). The primary outcome is to document histone acetylation and DNA methyltransferase expression (DNMT) in saliva collected from participants when comparing valproic acid arm with placebo arm.

Chemoprevention is an attractive strategy to reduce the incidence of squamous cell carcinoma of the head and neck, although past trials have not demonstrated its feasibility.

Valproic acid (VA) is a modifier of epigenetic events as it is an histone deacetylase inhibitor and causes DNMT degradation. The histone deacetylase inhibitors (e.g. VA) encompasses a new class of anti-tumor drugs, that can affect multiple pathways related to tumor initiation and progression due to histone and non-histone protein acetylation and DNMT degradation. VA promote histone acetylation when orally administered with a dose of 20-40 mg/kg, per day or 1000/1500 mg, per day.

Initially the authors will study saliva from participants documenting if there is saliva histone acetylation and if a difference in DNMT expression in saliva exists when comparing valproic acid arm to placebo arm (biological validation) after giving placebo or valproic acid for three months.

This will be the initial step of a bigger project. If authors prove that there will be a difference in histone acetylation and/or DNMT expression between groups they will launch a randomized, double blind, placebo control clinical trial (phase 3 clinical trial), to evaluate VA action as a chemopreventive agent in HNSCC patients who usually carries a high chance to develop recurrence (stages III/IV) or second primary malignancies (stages I/II/III/IV).

Chemoprevention of Head and Neck Squamous Cell Carcinoma (HNSCC) With Valproic Acid

Phase 0 Clinical Trial With Valproic Acid as a Chemopreventive Agent in Patients With Head and Neck Squamous Cell Carcinoma Previously Treated

As soon as we have results they will be shared.

Saliva samples will be collected in baseline and three months after study enrolment. Histone acetylation will be quantified (through ELISA method) and compared in the same arm (if there will be a change in histone acetylation when looking at these different timelines) and between arms (if one group will have or will not have more histone acetylation than the other).

Evaluation of incidence of treatment-induced adverse events at the beginning of each new cycle (day 1, every 30 days, for a total of six months) using Common Toxicity Criteria for Adverse Effects (CTCAE v.4.0).

Saliva samples will be collected in baseline and three months after study enrolment. DNA methyltransferases expression (through microarray method) will be compared in the same arm (if there will be a change in DNMT expression when looking at these different timelines) and between arms (if one group will have or will not have a different DNMT expression when compared to the other).

Barretos Cancer Hospital

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Lymphoma

Hyperplasia

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Antibodies

Immunoglobulins

This study involves a broad panel of lymphoma and lymphoid samples, which were previously procured under multiple protocols at the NIH, and for which there is excess tissue available for research.

David L Levens, M.D.

BACKGROUND:

Lymphomas are comprised of a diversity of tumors with different pathologic and clinical features. While distinct differences in gene expression profiles have been elucidated in different lymphomas, there has been inconsistent correlation with the few published proteomic studies.

Greater insights into the biology of lymphomas may be achieved by integrating current genomic information with additional studies focused on the interrelationships in tumors of the patterns of chromatin protein expression, chromatin protein modification, and RNA expression profiling (both within bulk tumor and within specific microscopic tumor niches accessible by microdissection and cell sorting approaches).

OBJECTIVES:

The goals of this protocol are to identify the global levels of all histones (including variant histones) and non-histone chromosomal proteins, and to measure the relative levels of most known covalent modifications on histone and non-histone chromosomal proteins.

For a limited number of cases illustrative of selected pathological entities, we propose to map the genome-wide distribution of those modifications judged to be biochemically instructive.

ELIGIBILITY:

This work will involve the analysis of a broad panel of lymphoma and lymphoid samples, which were previously procured under multiple protocols at the NIH, and for which there is excess tissue available for research. We also request permission to extend this analysis to surplus materials to be accrued under existing protocols, upon completion of all superseding diagnostic tests and medical/scientific studies. The criteria for inclusion in this study are subsumed under the enveloping protocols. The number of cases to be included is dependent upon the size of these protocols; because statistical significance improves with increasing numbers. We hope to include up to 300 cases.

DESIGN:

Lysates from surplus samples will be prepared and arrayed onto microarrays.

These arrays will be probed with panels of protein and modification specific antibodies.

The antibody reactivity will be quantified and samples will be subjected to statistical analysis, especially hierarchical clustering to correlate patterns of reactivity with clinical and histological features.

Representative cases for which sufficient surplus tissue remains will be subjected to ChIP-Seq to map the distribution of modifications across the genome.

Proteomic-Based Profiling of Lymphomas: Chromatin Proteomics; Composition and Modification of Histone and Non-Histone Chromosomal Proteins

global histone protein expression and covalent modification profiles from lymphoid cells

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Dose-Escalation Study of OBP-801 in Patients With Advanced Solid Tumors	NCT02414516	Solid Tumor	OBP-801	18 Years -	Oncolys BioPharma Inc
A Dose-Escalation Study of OBP-801 in Patients With Advanced Solid Tumors	NCT02414516	Solid Tumor	OBP-801	18 Years -	Oncolys BioPharma Inc
Chemoprevention of Head and Neck Squamous Cell Carcinoma (HNSCC) With Valproic Acid	NCT02608736	Head and Neck S...	Valproic Acid Placebo	18 Years -	Barretos Cancer Hospital
Proteomic-Based Profiling of Lymphomas: Chromatin Proteomics; Composition and Modification of Histone and Non-Histone Chromosomal Proteins	NCT01563874	Lymphoma Lymphoid Hyperp...		18 Years -	National Institutes of Health Clinical Center (CC)
Chemoprevention of Head and Neck Squamous Cell Carcinoma (HNSCC) With Valproic Acid	NCT02608736	Head and Neck S...	Valproic Acid Placebo	18 Years -	Barretos Cancer Hospital
Proteomic-Based Profiling of Lymphomas: Chromatin Proteomics; Composition and Modification of Histone and Non-Histone Chromosomal Proteins	NCT01563874	Lymphoma Lymphoid Hyperp...		18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for acetylation

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Spots Global Cancer Trial Database for acetylation

Every month we try and update this database with for acetylation cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for acetylation cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.