Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Fulvestrant

Estrogens

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Entinostat

Histone Deacetylase Inhibitors

Antineoplastic Agents, Hormonal

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Enzyme Inhibitors

Arm A: Fulvestrant (500 mg on C1D1, C1D15, C2D1, and on Day 1 of each subsequent cycle) plus entinostat (5 mg PO once weekly)

Arm B: Fulvestrant (500 mg on C1D1, C1D15, C2D1, and on Day 1 of each subsequent cycle) plus placebo (5 mg PO once weekly)

Placebo

Denise Yardley, MD

Preclinical data has demonstrated that entinostat (SNDX-275) can enhance fulvestrant sensitivity in hormone receptor-positive breast cancer in animal models. The addition of entinostat to fulvestrant will provide clinical benefit to patients with locally advanced or metastatic breast when compared to fulvestrant plus placebo. Also, based on previous data, patients exposed to entinostat who demonstrate an elevated level of protein lysine acetylation will have an improved efficacy outcome.

Entinostat (SNDX-275) inhibits mechanisms of resistance to hormone therapy in breast cancer (BC) cells, thereby prolonging sensitivity of the cells to fulvestrant. Preclinical data has demonstrated that entinostat can enhance fulvestrant sensitivity in hormone receptor-positive BC in animal models. Thus, it is hypothesized that the addition of entinostat to fulvestrant will provide clinical benefit to patients with locally advanced or metastatic BC when compared to fulvestrant plus placebo.

Preliminary data from Phase 2 Study SNDX-275-0301 suggest patients with higher levels of protein lysine acetylation who receive entinostat with exemestane potentially have improved clinical outcomes (e.g., PFS, OS) when compared to patients with lower levels of protein lysine acetylation. Thus, it is hypothesized that patients exposed to entinostat and who demonstrate an elevated level of protein lysine acetylation will have an improved efficacy outcome.

Phase 2 Study of Fulvestrant With and Without Entinostat in Postmenopausal Women With ER+ Advanced Breast Cancer

A Phase 2, Randomized, Double-Blind, Multicenter Study of Fulvestrant With and Without Entinostat in Postmenopausal Women With Hormone Receptor-Positive Advanced Breast Cancer

molecular classification of breast cancer (BC) subtypes, DNA methylation, e-cadherin levels, protein lysine acetylation levels, and changes in proteins associated with estrogen signaling and fulvestrant resistance

Syndax Pharmaceuticals

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Sarcoma

Carcinosarcoma

Mixed Tumor, Mullerian

Leiomyosarcoma

Endometrial Stromal Tumors

Adenoma, Pleomorphic

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Endometrial Neoplasms

Uterine Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Soft Tissue Sarcoma

Malignant Mixed Mullerian Tumor

Uterine Sarcoma

Uterine Carcinosarcoma

Vorinostat

Vorinostat, 400 mg orally once daily for the first 14 days of a 21 day cycle Treatment will be continued for 4 cycles. Patients with a response or stable disease after 4 cycles will be continued on vorinostat therapy at the tolerated schedule and dosage until disease progression, unacceptable toxicity or patients' withdrawal of the consent. At the maximum, a total of 12 cycles will be administered over a period of 9 months.

Vorinostat Oral Capsule

Edgar Petru, MD

Uterine sarcomas are rare tumors with a poor prognosis.

The main purpose of this phase II proof-of-principle- pilot study is to test the efficacy of the hydroxamic acid-based Histone deacetylase inhibitor (HDACI) Vorinostat (SAHA) as monotherapy in patients with HDAC-positive, progressive, metastatic uterine sarcomas and mixed epithelial and mesenchymal tumors after prior anti-proliferative therapy.

This is an open-label, single arm, proof of concept-study of the HDAC-inhibitor vorinostat in patients with refractory uterine sarcoma that have been pre-tested for an high expression of HDAC. Patients will receive Vorinostat, 400 mg (4 capsules á 100mg of Zolinza) orally once daily for the first 14 days of a 21 day cycle. Treatment will be continued for 4 cycles (treatment period 1). Patients with a response or stable disease after 4 cycles as determined by computed tomography (CT) of target an non target-lesions will be continued on vorinostat therapy at the tolerated schedule and dosage until disease progression, unacceptable toxicity or patients' withdrawal of the consent. At the maximum, a total of 12 cycles will be administered over a 9 months period (treatment periods 2 and 3).

The investigated condition occurs exclusively in women

Vorinostat (SAHA) in Uterine Sarcoma

A Pilot Study of Peroral Vorinostat (SAHA) in Patients With Refractory Histone Deacetylase-positive Uterine Sarcoma

Change from Baseline Tumor Size to last available observation with respect to progress as defined by RECIST 1.1 (CT-Scan every 12 weeks up to 9 months)

This endpoint is evaluated by the amount of clinical adverse experiences.

Medical University of Graz

Vorinostat Oral Capsules 400mg daily

Vorinostat Oral Capsule: Vorinostat, 400 mg orally once daily for the first 14 days of a 21 day cycle Treatment will be continued for 4 cycles. Patients with a response or stable disease after 4 cycles will be continued on vorinostat therapy at the tolerated schedule and dosage until disease progression, unacceptable toxicity or patients' withdrawal of the consent. At the maximum, a total of 12 cycles will be administered over a period of 9 months.

Vorinostat, Zolinza Oral Capsules

Age, Categorical

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Austria

Region of Enrollment

Statistical evaluation was not possible as only 1 Patient reached end point 1.

Prof. Edgar Petru

Only one Patient reached the first end Point. Statistical Evaluation was therefore not possible. For this reason no data are reported in the data table.

Progression-free Survival (PFS)

Only one Patient reached the first end Point. Statistical Evaluation was therefore not possible.

For this reason no data are reported in the data table.

Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

Overall Study

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Anticonvulsants

Central Nervous System Depressants

Psychotropic Drugs

Valproic Acid

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.

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).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 2 Study of Fulvestrant With and Without Entinostat in Postmenopausal Women With ER+ Advanced Breast Cancer	NCT02115594	Breast Cancer	Fulvestrant Entinostat Placebo	-	Syndax Pharmaceuticals
Vorinostat (SAHA) in Uterine Sarcoma	NCT03509207	Leiomyosarcoma Endometrial Str... Carcinosarcomas...	Vorinostat Oral...	18 Years -	Medical University of Graz
Phase 2 Study of Fulvestrant With and Without Entinostat in Postmenopausal Women With ER+ Advanced Breast Cancer	NCT02115594	Breast Cancer	Fulvestrant Entinostat Placebo	-	Syndax Pharmaceuticals
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
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

Spots Global Cancer Trial Database for histone deacetylases