Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Recurrence

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Reproductive Control Agents

Anti-Infective Agents

Tamoxifen

Everolimus

Letrozole

Medroxyprogesterone Acetate

Medroxyprogesterone

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Aromatase Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Contraceptive Agents

Contraceptives, Oral

Contraceptives, Oral, Hormonal

Contraceptive Agents, Female

Contraceptive Agents, Hormonal

Contraceptive Agents, Male

Everolimus 10 mg daily and Letrozole 2.5 mg PO daily

Tamoxifen 20 mg PO BID; on alternating weeks (even numbered) weeks, Medroxyprogesterone Acetate 200 mg PO daily with Tamoxifen 20 mg PO BID

20 mg daily by mouth on alternating weeks (even numbered) weeks

Brian Slomovitz, MD

The main purpose of this study is to evaluate the effectiveness of the combination of the drugs Everolimus and Letrozole compared to Tamoxifen and Medroxyprogesterone acetate in treating endometrial cancer and to determine the types and severity of side effects caused by treatment with these drug combinations.

Everolimus and Letrozole or Hormonal Therapy to Treat Endometrial Cancer

A Randomized Phase II Trial of Everolimus and Letrozole or Hormonal Therapy (Tamoxifen/Medroxyprogesterone Acetate) in Women With Advanced, Recurrent, or Persistent Endometria Carcinoma

To determine if relevant biomarkers correlate with response to treatment in each of the two arms. Unstained sections of tumor tissue will be used for hormone receptor (estrogen receptor-alpha, estrogen receptor-beta, progesterone receptor-A, progesterone receptor B and the G protein-coupled estrogen receptor, GPR-30) immunohistochemistry.

To determine if relevant biomarkers correlate with response to treatment in each of the two arms. Unstained sections of tumor tissue will be used for mTOR pathway (including phosphorylated S6 ribosomal protein, PTEN, total and phosphorylated AKT, total and phosphorylated mTOR, and phospho-ERK1/2) immunohistochemistry

To determine if relevant biomarkers correlate with response to treatment in each of the two arms. Unstained sections of tumor tissue and DNA extracted from whole blood will be used for mutational analysis (including PTEN, PIK3CA, KRAS, and CTNNB1 (beta-catenin) performed using a sequencing panel assay.

A confirmed complete or partial response as defined by RECIST 1.1 was considered a response. "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Progression-free Survival is defined as the duration alive from study entry until progression is documented, or death; whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions.

Maximum grade of physician assessed adverse events graded and categorized using Common Toxicity Criteria for Adverse Events (CTCAE) version 4

Survival is defined as the duration alive from study entry until death.

Novartis Pharmaceuticals

GOG Foundation

Collected on a 28 day cycle while treatment continues and then up to 30 days after the last cycle.

Everolimus 10 mg daily plus letrozole 2.5 mg PO daily in a 28 day cycle.

Everolimus and Letrozole

Tamoxifen 20 mg PO bid days 1-28 plus medroxyprogesterone acetate 200 mg PO days 8-14 and 22-28 repeating in a 28 day cycle.

Tamoxifen and Medroxyprogesterone Acetate

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Linda Gedeon for Virginia Filiaci, PhD

Eligible and treated participants. One participant in arm II was not treated. Participant flow contains all eligible participants.

Frequency of Response

Median Progression-free Survival

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Frequency and Severity of CTCAE (Common Toxicity Criteria for Adverse Events) Version 4

Median Survival

Hormone Receptor Immunohistochemistry

mTOR Pathway Immunohistochemistry

Mutation Analysis

Overall Study

Rare Diseases

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Analgesics

Interferons

Interleukin-2

Interferon-alpha

Interferon alpha-2

Antiviral Agents

Analgesics, Non-Narcotic

Interferon alfa

medroxyprogesterone acetate

Sylvie Negrier, MD, PhD

The PERCY Quattro trial has been designed to evaluate the survival benefit of two cytokine treatments, Interleukin-2 (IL2) and/or alpha interferon (IFN), for patients with intermediate chance of response in metastatic renal cell carcinoma.

Eligible patients will be randomly assigned in a two-by-two factorial design to either medroxyprogesterone (MPA), subcutaneous IFN, subcutaneous IL2, or a combination of IFN and IL2.

The primary objective of the study is overall survival; secondary objectives are progression-free survival, response rate, toxicity, and quality of life.

The PERCY Quattro trial has been designed to evaluate the survival benefit of Interleukin-2 (IL2) and/or alpha interferon (IFN) for patients with intermediate chance of response in metastatic renal cell carcinoma.

The primary objective is overall survival, and secondary objectives are progression-free survival, response rate, toxicity, and quality of life assessed before and after induction treatment (week 10).

Patients above 18 years of age are eligible if they have histologically confirmed, clearly progressive metastatic renal carcinoma, more than one metastatic organ and good performance status (Karnofsky score ≥80%), or one metastatic organ with Karnofsky score 80%, normal blood and liver functions with creatinine level \<= 160 µmol/L.

Eligible patients will be randomly assigned in a two-by-two factorial design to either medroxyprogesterone (MPA), subcutaneous IFN, subcutaneous IL2, or a combination of IFN and IL2. The planned sample size is 456 patients (114 in each of the four arms). MPA is given orally as 200 mg daily. IFN is given subcutaneously as 9 million IU three times a week. IL2 is given subcutaneously on a four-week schedule: 9 million IU twice daily for five days followed by a two-day rest, then, on the following three weeks, 9 million IU twice daily for two days then 9 million IU once daily on the following three days; after a week of rest, an identical 4-week cycle is administered. IFN and IL2 combination is given using identical routes, schedules and doses except for a reduction of IFN dose to 6 million IU per injection.

Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis

PERCY QUATTRO: Medroxyprogesterone, Interferon Alpha-2a, Interleukin 2 or Combination of Both Cytokines in Patients With Metastatic Renal Carcinoma of Intermediate Prognosis

French Immunotherapy Intergroup

SCAPP (Sub-Cutaneous Administration Proleukin Program)

Centre Leon Berard

Eye Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Nutritional and Metabolic Diseases

Hyperplasia

Endometrial Hyperplasia

Albinism

Hypoglycemic Agents

Metformin

Estradiol

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Polyestradiol phosphate

BIRC5 protein, human

Medicated with only 4mg/kg 17β estradiol hemihydrate for 20 days to develop endometrial hyperplasia

Having been obtained hyperplasia, the investigators continued medication with 50 mg/kg metformin in addition to 17β estradiol hemihydrate for 10 days

Having been obtained hyperplasia, the investigators continued medication with 1mg/day medroxyprogesterone acetate in addition to 17β estradiol hemihydrate for 10 days

17β estradiol hemihydrate

Erdem SAHİN

The purpose of the study is to determine apoptotic signaling pathways such as Survivin, Bcl-2, Bax, c-Myc and caspase-9 expression levels in rats model with iatrogenic endometrial hyperplasia after metformin and medroxyprogesterone acetate administration.

Apoptotic Signaling Pathways in Rats With Endometrial Hyperplasia

The Effect of Metformin and Medroxyprogesterone Acetate on Apoptotic Signaling Pathways in Wistar-Albino Rats With Induced Endometrial Hyperplasia

Kayseri Education and Research Hospital

Principal Investigator

Gland and Hormone Related Diseases

Carcinoma, Endometrioid

Ovarian Neoplasms

Ovarian Diseases

Adnexal Diseases

Gonadal Disorders

Endocrine System Diseases

Ovarian Cancer

Antipyretics

Acetaminophen

Entinostat

Histone Deacetylase Inhibitors

Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.

Patients receive medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Patients undergo hysterectomy between days 21-24.

Hysterectomy

Laboratory Biomarker Analysis

Linda R Duska

This randomized surgical window trial evaluates the effect of adding entinostat to medroxyprogesterone acetate before surgery works on progesterone receptors on endometrioid endometrial tumors. Medroxyprogesterone acetate is a progesterone, a hormone produced by body normally. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving medroxyprogesterone acetate with or without entinostat may effect tumors from endometrioid endometrial cancer.

PRIMARY OBJECTIVES:

I. To determine whether the addition of the histone deacetylase inhibitor, entinostat, in combination with medroxyprogesterone acetate in the pre-operative setting results in up-regulation of activated progesterone receptors (PR) compared to medroxyprogesterone acetate alone.

SECONDARY OBJECTIVES:

I. To assess the response rate (as measured by cellular morphology and proliferation) and change in activated receptor levels with the addition of entinostat at the time of hysterectomy.

OUTLINE: Two arms were randomly allocated to eligible patients with equal probability.

ARM I: Patients receive medroxyprogesterone acetate intramuscularly (IM) on day 1 and undergo hysterectomy between days 21-24.

ARM II: Patients receive medroxyprogesterone acetate IM on day 1 and entinostat orally (PO) on days 1, 8, and 15. Patients undergo hysterectomy between days 21-24.

Medroxyprogesterone Acetate With or Without Entinostat Before Surgery in Treating Patients With Endometrioid Endometrial Cancer

A Randomized Surgical Window Pilot Investigation of the Relationship of Short Term Medroxyprogesterone Acetate (NSC #26386) Compared to Medroxyprogesterone Acetate Plus Entinostat (NSC #706995) on the Morphologic, Biochemical, and Molecular Changes in Primary Endometrioid Adenocarcinoma of the Uterine Corpus

The H-score is defined as the percent cells staining positive (0-100) multiplied by the staining intensity (0, 1, 2 or 3) measured in the tumor by immunohistochemistry and averaged over 3 reviewers. This score can range from 0 to 300. In general, PRs are expected to decrease in response to medroxyprogesterone acetate. It was hypothesized that entinostat would mitigate the decrease in PR relative to the medroxyprogesterone acetate only arm post treatment. Higher PR H-scores post treatment in the arm with entinostat relative to the medroxyprogesterone alone arm would be consistent with this hypothesis. Arm II was thought to result in higher scores which was expected to have a more favorable outcome when treated with MPA therapy.

Pre- and post-treatment slides for each patient were evaluated in pairs for complete or partial histologic response by one reviewer. Pre- and post-treatment slides for each patient were evaluated in pairs for complete or partial histologic response by one reviewer. A histologic response was defined as either the absence of identifiable adenocarcinoma in the hysterectomy specimen section (complete) or, subjectively, as the presence of a complex proliferation of glands that retain the architectural characteristics of adenocarcinoma, but with features of secretion, decreased nuclear stratification, or the presence of eosinophilic, squamous or mucinous metaplasia, when this was absent in the initial sample (partial).

A response was defined as a decrease in Ki-67 protein expression in tumor from pre- to post-treatment.

Maximum grade of physician assessed adverse events reported during treatment and up to 45 days after surgery. Grades start with 1 which is considered mild through grade 5 which is death. Participants on this study had adverse event grades up to grade 3 which is considered moderately severe.

NRG Oncology

National Cancer Institute (NCI)

There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. No AEs were reported.

Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA

Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.

Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat

30-49 years

50-59 years

60-69 years

70-99 years

Age, Customized

Participants with Endometrioid Cell Type Cancer

Randomized, treated, evaluable specimen. There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. There were two additional patients with insufficient tumor post-treatment and no slides were submitted; one in each reporting group. There was one additional patient with no specimens submitted in reporting group 2.

Mean Post-treatment Tumor Progesterone Receptor H-score (Histology Score)

Randomized, treated, evaluable pre and post treatment specimen available. There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. There was one participant with an inevaluable pre-treatment slide. There were two additional patients with insufficient tumor post-treatment and no slides were submitted; one in each reporting group. There was one additional patient with no specimens submitted in reporting group 2.

Percentage of Participants With a Histologic Response

Randomized, treated, evaluable pre and post treatment specimens available. There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. There was one participant with an inevaluable pre-treatment slide. There were two additional patients with insufficient tumor post-treatment and no slides were submitted; one in each reporting group. There was one additional patient with no specimens submitted in reporting group

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Everolimus and Letrozole or Hormonal Therapy to Treat Endometrial Cancer	NCT02228681	Advanced, Persi...	Everolimus Tamoxifen Letrozole Medroxyprogeste...	18 Years -	GOG Foundation
Everolimus and Letrozole or Hormonal Therapy to Treat Endometrial Cancer	NCT02228681	Advanced, Persi...	Everolimus Tamoxifen Letrozole Medroxyprogeste...	18 Years -	GOG Foundation
Everolimus and Letrozole or Hormonal Therapy to Treat Endometrial Cancer	NCT02228681	Advanced, Persi...	Everolimus Tamoxifen Letrozole Medroxyprogeste...	18 Years -	GOG Foundation
Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis	NCT00291369	Metastatic Rena...	Interleukin-2 Interferon alfa medroxyprogeste...	18 Years -	Centre Leon Berard
Apoptotic Signaling Pathways in Rats With Endometrial Hyperplasia	NCT02872818	Apoptotic Signa...	17β estradiol h... Metformin medroxyprogeste...	8 Weeks - 10 Weeks	Kayseri Education and Research Hospital
Medroxyprogesterone Acetate With or Without Entinostat Before Surgery in Treating Patients With Endometrioid Endometrial Cancer	NCT03018249	FIGO Grade 1 En... FIGO Grade 2 En... FIGO Grade 3 En...	Entinostat Hysterectomy Laboratory Biom... Medroxyprogeste...	18 Years -	National Cancer Institute (NCI)
Medroxyprogesterone Acetate With or Without Entinostat Before Surgery in Treating Patients With Endometrioid Endometrial Cancer	NCT03018249	FIGO Grade 1 En... FIGO Grade 2 En... FIGO Grade 3 En...	Entinostat Hysterectomy Laboratory Biom... Medroxyprogeste...	18 Years -	National Cancer Institute (NCI)
Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis	NCT00291369	Metastatic Rena...	Interleukin-2 Interferon alfa medroxyprogeste...	18 Years -	Centre Leon Berard
Treatment of Hot Flushes Caused by Leuprorelin 11.25 mg in Prostate Adenocarcinoma	NCT01011751	Adenocarcinoma,...	Cyproterone ace... Medroxyprogeste... Venlafaxine Leuprorelin Flutamide Placebo	18 Years -	Takeda
Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features	NCT05255653	Endometrial Can...	Olaparib Pelvic external... Chemotherapy Durvalumab Medroxyprogeste... Megestrol Aceta... Vaginal brachyt... Observation	18 Years -	Leiden University Medical Center

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