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Urinary Tract, Sexual Organs, and Pregnancy Conditions

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Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

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Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

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Ovarian Cancer

Ovarian Epithelial Cancer

Ovarian Low Malignant Potential Tumor

Anti-Inflammatory Agents

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All Drugs and Chemicals

Micronutrients

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Dexamethasone

Dexamethasone acetate

BB 1101

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Antineoplastic Agents, Hormonal

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Folinic Acid

Folate

Vitamin B9

Patients receive valproic acid PO BID on days -7 to -3 and QD on day -2 and dexamethasone PO QD on days -5 and -2 and BID on days -4 and -3. Patients undergo collection of serum and tissue samples for analysis via PCR and IHC at baseline, time of surgery, and 7-14 days after surgery.

Patients receive valproic acid PO BID on days -7 to -3 and QD on day -2 and dexamethasone PO QD on days -5 and -2 and BID on days -4 and -3. Patients undergo collection of serum samples for analysis via PCR and IHC at the time of clinically suspected recurrence, 2 days after completion of induction, and 7-14 days after induction.

Laboratory Biomarker Analysis

Ira Winer

This pilot research trial studies folate receptor in diagnosing ovarian cancer using serum samples from patients with a newly diagnosed pelvic mass or previously diagnosed ovarian cancer. Studying samples of serum from patients with ovarian cancer in the laboratory may help understand the use of folate receptor induction as a clinical tool in initial diagnosis, surveillance, and recurrence.

PRIMARY OBJECTIVES:

I. To evaluate the pre- and post-induction correlation between soluble folate receptor and tumor-based receptor levels as a marker of malignancy in patients with newly diagnosed adnexal masses. (Arm I) II. To evaluate the ability to induce serum folate receptor (FR) with dexamethasone (Dex) and valproic acid (VPA) treatment in patients with newly diagnosed adnexal masses. (Arm I) III. To evaluate the use of the serum soluble FR as a marker for earlier detection of recurrent disease. (Arm II) IV. To evaluate the ability to induce FR with Dex and VPA in the setting of recurrent disease. (Arm II)

SECONDARY OBJECTIVES:

I. To evaluate the expression of FR in primary versus (vs.) metastatic tumor sites in patients with ovarian malignancy undergoing Dex and VPA induction and correlate expression with other markers associated with malignancy (marker of proliferation Ki-67 \[Ki67\], cancer antigen \[CA\]-125, etc.).

II. To analyze the correlation between gluco-corticoid receptor (GR) levels and serum FR induction efficacy.

III. To examine global, downstream targets of GR and FR induction in patient samples undergoing treatment with Dex and VPA.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I (INDUCTION): Patients receive valproic acid orally (PO) twice daily (BID) on days -7 to -3 and once daily (QD) on day -2 and dexamethasone PO QD on days -5 and -2 and BID on days -4 and -3. Patients undergo collection of serum and tissue samples for analysis via polymerase chain reaction (PCR) and immunohistochemistry (IHC) at baseline, time of surgery, and 7-14 days after surgery.

ARM II (SURVEILLANCE AND RECURRENCE): Patients receive valproic acid PO BID on days -7 to -3 and QD on day -2 and dexamethasone PO QD on days -5 and -2 and BID on days -4 and -3. Patients undergo collection of serum and tissue samples for analysis via PCR and IHC at the time of clinically suspected recurrence, 2 days after completion of induction, and 7-14 days after induction.

Folate Receptor in Diagnosing Ovarian Cancer Using Serum Samples From Patients With Newly Diagnosed Pelvic Mass or Previously Diagnosed Ovarian Cancer

Study of Serum Measured Folate Receptor and Its Induction as a Biomarker in the Diagnosis and Surveillance of Ovarian Carcinoma

FR will be measured in the serum of patients utilizing a standardized tritiated folate/charcoal binding assay pre- and post-drug administration. This will be measured to the femto-molar level. Two sided t-tests will be utilized as a baseline statistical analysis to determine the efficacy of induction in this setting.

Folate receptor levels in patients with benign and malignant conditions will be compared utilizing receiver operator curves for both pre- and post-induction levels to determine if soluble folate receptor can be utilized as a tumor marker in newly diagnosed adnexal masses and/or ovarian cancer. Both two-sided t tests and ROC curve analysis will be utilized in this portion of the analysis.

Patients are to be followed during surveillance period for a history of know ovarian carcinoma with serum FR in addition to CA-125. FR will again be measured in the serum of patients utilizing a standardized tritiated folate/charcoal binding assay. This will be measured to the femto-molar level. ROC curve analysis will be performed to evaluate the efficacy of baseline Folate Receptor in early detection of relapse and compared to standard tumor markers such as CA-125.

If recurrence is suspected, this portion of Arm 2 is meant to determine if serum levels of FR can be artificially increased in the recurrent setting utilizing DEX and VA above baseline recurrent levels. FR will be measured in the serum of patients utilizing a standardized tritiated folate/charcoal binding assay pre- and post-drug administration. This will be measured to the femto-molar level. Two side t-tests will be utilized to determine the efficacy of induction in this setting.

Two sided independent t-tests will be performed to compare the expression of FR in primary vs metastatic tumor sites. Pearson's correlation coefficients will be calculated to evaluate the associations between serum FR and existing markers such as Ki67 and CA-125.

Achieved by utilizing such techniques (but not limited to) as transcriptome analysis and whole genome Chip analysis.

Pearson's correlation coefficients will be calculated to evaluate the associations between serum Folate receptor levels and tissue based glucocorticoid receptors.

National Cancer Institute (NCI)

Barbara Ann Karmanos Cancer Institute

Principal Investigator

Adenocarcinoma

Adenocarcinoma, Clear Cell

Adenomyoepithelioma

Carcinoma, Endometrioid

Endometrial Neoplasms

Uterine Neoplasms

Epithelial-myoepithelial Carcinoma

Subjects will be treated with NXP800 at 50 mg/day.

Subjects will be treated with NXP800 at 75 mg/day.

NXP800 is an anti-neoplastic, oral small molecule.

NXP800

Diane Marsolini

Shay Shemesh, MSc

Alexandrea Cronin

Kassie DiOrio

Melissa Barnes

Ashley Douglas, RN, BSN, OCN

Ruth Orr

Udai Banerji, Prof

Susana Banerjee, Dr

The purpose of the dose escalation phase is to evaluate the safety profile of escalating doses and dose schedules of NXP800. In the expansion phase the preliminary efficacy in subjects with ARID1a mutated ovarian clear cell and ovarian endometrioid cancers will be estimated.

Part A of the study is a dose escalation by cohort study of NXP800 administered to patients with advanced cancers. The study will identify the maximum tolerated dose (MTD) and propose dose and dose schedules for future studies.

In Part B doses selected in Part A are administered to patients with platinum-resistant, ARID1a-mutated ovarian carcinoma.

Part A dose escalation followed by Part B, expansion in ovarian cancers.

Part B is enrolling ovarian cancer patients.

A Phase 1 Clinical Study of NXP800 in Subjects With Advanced Cancers and Expansion in Subjects With Ovarian Cancer

European Network of Gynaecological Oncological Trial Groups (ENGOT)

GOG Foundation

Nuvectis Pharma, Inc.

Uterine Diseases

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

SP-2577

Open-label study of SF-2577 plus pembrolizumab in advanced, recurrent small cell ovarian cancer as well as select additional ovarian and endometrial cancers within the SWI/SNF pathway.

This study is an open-label, non-randomized dose escalation and expansion study of the LSD inhibitor SP-2577 in combination with the anti PD- 1 antibody pembrolizumab in patients with advanced, recurrent small cell ovarian cancer of the hypercalcemic type (SCCOHT) as well as select additional ovarian and endometrial cancers with mutations in the genes within the SWI/SNF pathway (Ovarian Clear Cell Cancers (OCCC), Endometrioid Ovarian Cancers (EOC) and Endometrioid Endometrial Cancers (EEC).

Type of cancer being evaluated (ovarian and endometrial)

Pilot Trial of SP-2577 Plus Pembrolizumab in Select Gynecologic Cancers

Pilot Feasibility and Efficacy Trial of a Novel Reversible LSD1 Inhibitor SP-2577 (Seclidemstat) Plus Pembrolizumab in Select SWI/SNF-mutant Gynecologic Cancers

Incidence of Adverse Events (AEs) as measured by NCI CTCAE version 5.0

Incidence of dose-limiting toxicities (DLTs) during the dose escalation phase

Percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR), as determined by Investigator according to Response Evaluation in Solid Tumors (RECIST) v 1.1

Percentage of participants with Disease Control (complete response, partial response, or stable disease) as determined by RECIST v1.1

Duration of Response as determined by the Investigator according to RECIST v1.1

Duration of Stable Disease as determined by the investigator according to RECIST v 1.1

Progression Free Survival (PFS) as determined by the Investigator according to RECIST v1.1

Overall Survival (OS) as determined by the Investigator according to RECIST v1.1

Plasma concentration of seclidemstat (SP-2577)

Proportion of circulating tumor DNA ( ctDNA) in peripheral blood and other body fluids e.g. ascitic fluid

Percentage of target inhibition by seclidemstat and pembrolizumab in tumor tissue biopsy specimens

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Folate Receptor in Diagnosing Ovarian Cancer Using Serum Samples From Patients With Newly Diagnosed Pelvic Mass or Previously Diagnosed Ovarian Cancer	NCT02520115	Adnexal Mass Borderline Ovar... Ovarian Clear C... Ovarian Endomet... Ovarian Neoplas... Ovarian Serous ... Recurrent Ovari...	Dexamethasone Laboratory Biom... Valproic Acid	18 Years -	Barbara Ann Karmanos Cancer Institute
A Phase 1 Clinical Study of NXP800 in Subjects With Advanced Cancers and Expansion in Subjects With Ovarian Cancer	NCT05226507	Advanced Solid ... Ovarian Cancer Ovarian Clear C... Ovarian Clear C... Ovarian Clear C... Ovarian Endomet... Ovarian Endomet... ARID1A Gene Mut...	NXP800	18 Years -	Nuvectis Pharma, Inc.
Pilot Trial of SP-2577 Plus Pembrolizumab in Select Gynecologic Cancers	NCT04611139	SCCOHT Ovarian Clear C... Ovarian Endomet... Endometrial Can...	SP-2577 Pembrolizumab	18 Years -	HonorHealth Research Institute
Pilot Trial of SP-2577 Plus Pembrolizumab in Select Gynecologic Cancers	NCT04611139	SCCOHT Ovarian Clear C... Ovarian Endomet... Endometrial Can...	SP-2577 Pembrolizumab	18 Years -	HonorHealth Research Institute

Spots Global Cancer Trial Database for ovarian clear cell tumor