Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Syndrome

Polycystic Ovary Syndrome

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

All Drugs and Chemicals

Reproductive Control Agents

Antineoplastic Agents

Hormones

Estrogens

Progestins

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Estradiol

Polyestradiol phosphate

Triptorelin Pamoate

Cetrorelix

Dydrogesterone

Progesterone

Chorionic Gonadotropin

Menotropins

Hormone Antagonists

Contraceptive Agents

Contraceptive Agents, Hormonal

Contraceptive Agents, Female

Antineoplastic Agents, Hormonal

Patients will be coadministered with Human Menopausal Gonadotrophin (HMG) 150-225 international unit/day (IU/d) via intramuscular injection and oral DYG 20mg/d from menstrual cycle day 3 (MC3) to the day of triggering. The starting dose of HMG is 150IU/day for patients with a high antral follicle count \>20 or slightly elevated basal FSH (7-10IU/L), and a daily dose of 225IU HMG is used for the other patients. The dose will be adjusted after day 5 of stimulation based on the ovarian response as assessed by serum hormone levels and transvaginal ultrasonography

In the fixed GnRH antagonist protocol, daily s.c. administration of Cetrotide 0.25 mg will be initiated at 6th day of stimulation. HMG (150-225IU) will be administered daily from menstrual cycle day 3, and follicular monitoring will be performed every 2 to 3 days after 5 days of injections. The dose of hMG will be adjusted according to the ovarian response, as monitored by ultrasonography and the measurement of serum sex steroids. Treatment with hMG and GnRH antagonist will continue daily until the day when final oocyte maturation is triggered

first arm will be coadministered gonadotrophins with 20mg dydrogesterone till day of trigger second arm will be subjected to fixed GnRH antagonist protocol then will do Freeze All in both arms then frozen embryo transfer next cycle

Dydrogesterone Tablets

In the fixed GnRH antagonist protocol, daily s.c. administration of Cetrotide 0.25 mg will be initiated at 6th day of stimulation. HMG (150-225IU) will be administered daily from menstrual cycle day 3.

cetrorelix 0.25mg

(150-225IU) will be administered daily from menstrual cycle day 3 till day ot trigger

human menopausal gonadotropin

When the dominant follicles reach a diameter of 18mm, the final stage of oocyte maturation will be induced with injections of 100µg of triptorelin s.c combined with 1000IU of hCG i.m

triptorelin 0.1 mg

human chorionic gonadotropin

All of the follicles greater than 10mm in diameter will be aspirated. The oocytes are inseminated approximately 4-6hours after follicular aspiration by a conventional IVF method or intracytoplasmic sperm injection, based on the sperm quality On day 3, high quality embryos are cryopreserved by means of vitrification

cryopreservation

Endometrium will be prepared using step-up oral estrogen protocols. On day 14 of estrogen administration, endometrial thickness will be assessed and serum progesterone level will be measured, with cycles to be cancelled according to the arbitrary thresholds of 7.0 mm and 1.5 ng/mL, respectively. Progesterone administration will be started on the morning (am) of day 15, with the start date of progesterone and the day of blastocyst cryopreservation used to coordinate the day of FET

Estradiol Valerate and progesterone

Ahmed Elawady, MD

The purpose of this trial is to compare the efficacy and safety of the PPOS protocol to the GnRH antagonist protocol in patients with PCOS who are undergoing IVF/ICSI cycles.

Polycystic ovary syndrome (PCOS) is a common metabolic dysfunction and heterogeneous endocrine disorder. It is the most common cause of anovulatory infertility, affecting approximately 10%-18% of reproductive age women worldwide.

It is usually characterized by a clustering of hyperandrogenism, hypersecretion of luteinizing hormone (LH) and hyperinsulinaemia, which could result in the arrest of ovarian follicular growth, oligo-ovulation or anovulation, menstrual dysfunction, hirsutism, infertility, pregnancy and/or neonatal complications.

Women with PCOS undergoing IVF or Intracytoplasmic sperm injection (ICSI) treatment because of infertility are increasing in number, and these patients have been well described, typically characterized by producing an increased number of oocytes but are often of poor quality leading to lower fertilization, implantation, and pregnancy rates and a higher miscarriage rate and incidence of ovarian hyperstimulation syndrome.

Increasing evidence raises the issue that impaired oocyte maturation and developmental competence in women with PCOS are possibly linked to abnormal endocrine/ paracrine factors, metabolic dysfunction and alterations in the intrafollicular microenvironment during folliculogenesis and follicle maturation.

Several clinical ovarian stimulation protocols have been used so far in women with PCOS undergoing IVF treatment to prevent a premature LH surge during controlled ovarian stimulation (COS); these primarily include gonadotropin-releasing hormone (GnRH) agonist or antagonist protocols.

GnRH antagonists can competitively inhibit endogenous GnRH and produce an immediate and rapid decline in LH and Follicle-stimulating hormone (FSH) levels without the flare effect of a GnRH agonist, and their administration by subcutaneous injection in the late follicular phase prevents an LH surge.

With progress in embryo vitrification techniques, many studies have suggested that pregnancies that arise from the transfer of frozen-thawed IVF embryos appear to have better perinatal and pregnancy outcomes. Thus, GnRH antagonist regimens combined with a freeze-all strategy for women with PCOS are currently accepted as the most routine IVF procedures.

The progesterone's pituitary suppression was recently used in controlled ovarian stimulation and approved its efficacy in terms of low incidence of premature LH surge and comparable pregnancy outcomes to short protocols in infertile women of normal ovarian reserve and polycystic ovarian syndrome.

These data indicated that progestin treatment might improve oocyte quality compared with a GnRH antagonist during COS in these patients, plus there were the advantages of an oral administration route instead of repeated injections of GnRH antagonist, a lower drug price and more control over LH levels, which can reduce the patients' discomfort and costs.

Furthermore, to avoid a low response of the hypothalamic pituitary ovarian axis, a double trigger with GnRHa and a low dose of Human chorionic gonadotropin (hCG)(1000IU) was used to induce final oocyte maturation without increasing the risk of moderate or severe Ovarian hyperstimulation syndrome (OHSS).

Choosing the appropriate progestin is crucial to the success of the Progestin-primed ovarian stimulation protocol (PPOS). Previous studies have shown that both Medroxyprogesterone acetate (MPA) and Utrogestan are effective oral alternatives for the PPOS protocol.

MPA is preferred over Utrogestan because the administration of a natural exogenous progesterone, such as Utrogestan, can interfere with serum progesterone measurement and lead to the neglect of possible premature luteinization. However, the use of MPA during ovarian stimulation may lead to stronger pituitary suppression and thus may require a higher dosage of gonadotrophin and a longer ovarian stimulation duration than that of the conventional ovarian stimulation protocol. Therefore, the investigators need to test more synthetic progestins to find the most suitable option for PPOS.

Dydrogesterone (DYG), which has a molecular structure similar to that of natural progesterone, is widely used for hormone replacement therapy, endometriosis treatment, menstrual disorders and luteal support in pregnancy and threatened miscarriage. However, unlike MPA, the use of DYG under the recommended dosage (10-20 mg) does not inhibit ovulation, and thus, the use of DYG as an alternative to MPA and as an appropriate progestin in the PPOS regimen has yet to be explored.

In this study, the investigators hypothesize that DYG can be used as an alternative progestin in the PPOS protocol. A randomized controlled trial (RCT) is designed to investigate cycle characteristics and endocrinological profiles of patients taking gonadotrophin while using DYG co-treatment, and to compare pregnancy outcomes in first frozen embryo transfer (FET) cycles with GNRH antagonist protocol as a control.

Progestin-primed Ovarian Stimulation Protocol Versus GnRH Antagonist Protocol in Polycystic Ovary Syndrome Patients Undergoing IVF/ICSI Cycles

clinical pregnancy is defined as presence of gestational sac on ultrasound performed at 6 weeks after ET. A clinical pregnancy rate is defined as number of clinical pregnancies divided by number of ET procedures.

premature LH surge is increased serum LH more than twice the baseline or more than 15 Milli-international units per milli litre

number of embryos formed per 100 injected oocytes

number of gestational sacs per 100 transferred embryos

number of viable pregnancies beyond 8-10 weeks of gestation

delivery of any viable infant at 28 weeks or longer gestation after embryo transfer

Mansoura University

Immune System Diseases

Prostatic Neoplasms

Hypersensitivity

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases, Male

Prostatic Diseases

Male Urogenital Diseases

Androgens

Males who have been diagnosed with Prostate Cancer and are experiencing PSA rise, while taking androgen agonist therapy.

Richard Casey, M.D.

Alvaro Morales, M.D.

This Phase IV observational trial is intended to identify patients who are failing GnRH agonist therapy as evidenced by a rising PSA and who have yet to initiate secondary manoeuvres involving antiandrogens. This group may include both non-metastatic as well as metastatic patients. The trial will determine if these patients will benefit from switching to Degarelix. It will assess the effect of Degarelix's direct mode of action on androgen levels and whether continuous use of Degarelix improves disease progression.

As per the CUA Guidelines for the Management of CRPC, because the androgen receptor remains active in most patients who have developed castration resistant disease, it is recommended that ADT should be continued (LEVEL 3, GRADE C). Therefore, it is logical to continue patients on Degarelix throughout the castrate resistant period. This will allow for the gathering of data that is currently unknown within this setting, such as the effect of combined treatment with antiandrogens as well as chemotherapy and other castrate resistant treatments.

This trial will include hormone sensitive prostate cancer patients switched to Degarelix therapy after failing on GnRH agonists but prior to use of secondary hormonal treatments such as antiandrogens. The purpose of this trial is to determine the effect of Degarelix's direct mode of action on androgen levels and whether continuous use of Degarelix improves disease progression.

This is an open-label, multi-centre, Phase IV observational trial with s.c. injections of Degarelix one-month depot in patients with advanced prostate cancer.

The visit frequency is once a month (28-day intervals), with eCRF data entry at every 4 months. All patients will be treated with a one-month starting dose followed by 23 monthly maintenance doses for a duration of 672 days. The primary endpoints will be evaluated after 24 treatment months.

In total, 25 visits are scheduled for all patients.

Hormone Sensitive Prostate Cancer Patients Switched to Degarelix Therapy After Failing on GnRH Agonists

Hormone Sensitive Prostate Cancer Patients Switched to Degarelix Therapy After Failing on GnRH Agonists: A Prospective, Observational, Phase IV Study (DELAY)

To evaluate testosterone supression in hormone sensitive prostate cancer patients switched to Degarelix therapy after failing on GnRH agonists

To evaluate testosterone, bio available testosterone (calculated), prostate serum antigen (PSA), luteinizing hormone (LH) , follicle-stimulating hormone (FSH), dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA) before and after switching to Degarelix and over time

To evaluate PSA response (ability of Degarelix to stabilise or reverse PSA progression)

To evaluate how long patients are on degeralix prior to demonstrating biochemical disease progression (time to PSA failure)

To evaluate how long patients are on degeralix before they develop metastases (non-metastatic patients)

Eevaluate how long patients have been on degeralix before initiating chemotherapy.

Evaluate how long patients are on degeralix before initiating anti-androgen use as well as response to anti-androgen use

To evaluate patient performance status as defined by the Eastern Cooperative Oncology Group (ECOG).

Ferring Pharmaceuticals

CMX Research

Recurrence

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

IK-175 + nivolumab

Katherine Kim, MD

Karim Malek, MD

This is a phase 1b study in adult patients diagnosed with resistant or recurrent head and neck squamous cell carcinoma (HNSCC) designed to assess the safety and tolerability of IK-175 in combination with nivolumab. Disease response, pharmacokinetics (PK), pharmacodynamics, and response biomarkers will also be assessed.

This is an open-label, multicenter, phase 1b dose-expansion study to evaluate the safety, tolerability, preliminary antitumor activity, PK, and pharmacodynamics of 2 dose levels of IK-175, administered PO in combination with nivolumab, in patients with primary PD-1-resistant metastatic or locally incurable, recurrent HNSCC for which standard therapy is no longer effective or is intolerable.

Oral AHR Antagonist in Combination With Nivolumab in Patients With PD-1 Resistant Metastatic or Recurrent Head and Neck Cancer

A Phase 1b, Open-Label, Single-Arm Dose-Expansion Study of IK-175, an Oral Aryl Hydrocarbon Receptor Inhibitor, in Combination With Nivolumab in Patients With Primary PD-1 Inhibitor Resistant Metastatic or Locally Incurable, Recurrent HNSCC

Number and severity of TEAEs as assessed by CTCAE 5.0

Number and severity of TRAEs as assessed by CTCAE 5.0

Number and severity of SAEs as assessed by CTCAE 5.0

Number and severity of adverse events leading to dose modifications and/or treatment discontinuation as assessed by CTCAE 5.0

ORR is defined as the percentage of participants with confirmed complete response (cCR) or confirmed partial response (cPR) per RECIST 1.1

DCR is defined as the percentage of participants with no occurrence of progressive disease with either cCR, cPR, or stable disease \[SD\] ≥ 16 weeks per RECIST 1.1 from the beginning of study therapy

DOR is defined as the time from the first documented CR or PR per RECIST 1.1 until disease progression or death from any cause

PFS is defined as the length of time from the beginning of study treatment to the first observed disease progression or death due to any cause

OS is defined as the length of time from the beginning of study treatment to the date of death due to any cause

Bristol-Myers Squibb

Ikena Oncology

Rare Diseases

Kennedy Disease

Glucocorticoids

Patients will be treated with enzalutamide monotherapy once daily for 28 days followed by combination treatment with CORT125281 at escalating dose levels and enzalutamide once daily in 28-day dosing cycles.

Patients who have progressed during treatment with abiraterone and no other AR-blocking therapies will be treated with CORT125281 and enzalutamide.

Sub-Cohort (first 10 patients enrolled into Cohort A). Patients enrolled into this subcohort will receive a single dose of CORT125281 at Cycle 1 Day -7 and a single dose of CORT125281 at Cycle 1 Day 1 30 minutes after a standard breakfast to assess the effect of food on PK parameters. Patients will then begin CORT125281 in combination with enzalutamide on Cycle 1 Day 2 and continue in 28-day dosing cycles.

Patients who progressed during treatment with enzalutamide or second-generation AR-blocking therapies will be treated with a daily dose of CORT125281 and enzalutamide.

Patients randomized to this cohort will receive enzalutamide and a titrated dose of CORT125281. Enzalutamide will be continued at the dose currently tolerated by the patient at screening.

Patients randomized to this cohort will receive enzalutamide, placebo, and CORT125281.

CORT125281 is supplied as capsules for oral dosing

CORT125281

Enzalutamide (Xtandi)

Placebo capsules to match the appearance of the CORT125281

Placebo

William Guyer, PharmD

Grace Mann, PhD

This is an open-label, Phase 1/2a dose escalation study with an expansion phase to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD), and preliminary efficacy of CORT125281 in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) to identify a recommended dose (RD) for Phase 2 studies.

CORT125281 is a selective glucocorticoid receptor (GR) antagonist. In this study, CORT125281 will be administered orally in combination with enzalutamide to patients with metastatic castration-resistant prostate cancer (mCRPC) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the regimen. The study consists of two phases: a dose-determination phase and an expansion phase. The dose determination phase is designed to determine dose-limiting toxicities and the RD of CORT125281 plus enzalutamide in patients with mCRPC. Once the recommended dosing regimen has been determined, the following expansion cohorts will be enrolled and treated with CORT125281 plus enzalutamide at the recommended dose level.

Abi-Resistant Cohort: Patients who have progressed during treatment with abiraterone, and have received no other androgen receptor (AR)-blocking therapies

ARant-Resistant Cohort: Patients who have progressed during treatment with enzalutamide or other second-generation AR inhibitors.

The effect of food on CORT125281 PK will be assessed in a portion of the patients enrolled in the Expansion Phase. The two expansion cohorts will be enrolled in parallel.

In each phase of the study, routine assessments of safety and tolerability will be performed and samples will be collected to determine standard PK parameters for CORT125281, enzalutamide, and their major metabolites. PD, quality of life evaluations and preliminary evaluations of anti-tumor activity of CORT125281 with enzalutamide will be performed throughout the study.

Only patients with histologically confirmed metastatic castration-resistant prostate cancer will be considered for the study.

Study to Evaluate CORT125281 in Combination With Enzalutamide in Patients With mCRPC

Phase 1/2a Dose-Escalation and Expansion Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CORT125281 With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer

Determine the maximum tolerated dose (MTD) and/or biologically active doses of CORT125281 in combination with enzalutamide to identify the recommended dose (RD) for Phase 2 studies based on the number of patients with dose limiting toxicities (DLTs) of CORT125281 in combination with enzalutamide

The safety of each treatment group will be assessed by evaluating the incidence of treatment-related adverse events according to CTCAE v4.03

Area under the plasma concentration-time curve calculated using linear trapezoidal summation from time 0 to time last, where "last" is the time of the last measurable concentration

Area under the plasma concentration-time curve from 0 to 24 hours, calculated using linear trapezoidal summation

Area under the plasma concentration-time curve from 0 to infinity, calculated using the formula: AUC0-ing = AUC0-last + Clast/ λz, where λz is the apparent terminal elimination rate constant (whenever possible)

Minimum observed plasma concentration, at predose at steady-state

Time of the maximum plasma concentration (obtained without interpolation)

Terminal elimination rate constant (whenever possible)

Comparison of the fed state versus the fasted state comparison for the maximum observed plasma concentration (Cmax)

Comparison of the fed state versus fasted state comparison for area under the plasma concentration-time curve

Comparison of the fed state versus fasted state comparison for area under the plasma concentration-time curve to infinity

Determine the ORR by comparing the proportion of the patients who have either a complete response (CR) or partial response (PR)

Determine the proportion of patients with a reduction in PSA level by \>50%

Determine the time to SSE defined as symptomatic fracture, radiation or surgery to bone, or spinal cord compression

Determine rPFS defined as the time interval from first dose of study drug (CORT125281 and/or enzalutamide) to the date when the first site of disease is found to progress on CT, MRI, or radionucleotide bone scan per PCWG3, or death whichever occurs first; including the proportion of patients progression-free at 4, 6, and 12 months

Assess time to PSA progression, including the proportion of patients progression free at 4, 6, and 12 months

Assess time to clinical progression, including the proportion of patients progression free at 4, 6, and 12 months

Determine the DOR by the time from the first occurrence of a documented objective tumor response to the time of radiographic progression (per investigator using RECIST v1.1) or death from any cause on study, whichever occurs first

Determine OS by the time from the first dose of study drug (CORT125281 and/or enzalutamide) to the date of death from any cause

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Progestin-primed Ovarian Stimulation Protocol Versus GnRH Antagonist Protocol in Polycystic Ovary Syndrome Patients Undergoing IVF/ICSI Cycles	NCT05112692	PCOS (Polycysti...	Dydrogesterone ... cetrorelix 0.25... human menopausa... triptorelin 0.1... human chorionic... cryopreservatio... Estradiol Valer...	20 Years - 35 Years	Mansoura University
Hormone Sensitive Prostate Cancer Patients Switched to Degarelix Therapy After Failing on GnRH Agonists	NCT01366053	Prostate Cancer		18 Years -	CMX Research
Progestin-primed Ovarian Stimulation Protocol Versus GnRH Antagonist Protocol in Polycystic Ovary Syndrome Patients Undergoing IVF/ICSI Cycles	NCT05112692	PCOS (Polycysti...	Dydrogesterone ... cetrorelix 0.25... human menopausa... triptorelin 0.1... human chorionic... cryopreservatio... Estradiol Valer...	20 Years - 35 Years	Mansoura University
Oral AHR Antagonist in Combination With Nivolumab in Patients With PD-1 Resistant Metastatic or Recurrent Head and Neck Cancer	NCT05472506	Head and Neck S... Head and Neck C... Head Cancer Neck Cancer Head Cancer Nec... Neck Carcinoma	IK-175 + nivolu...	18 Years -	Ikena Oncology
Study to Evaluate CORT125281 in Combination With Enzalutamide in Patients With mCRPC	NCT03437941	Metastatic Cast...	CORT125281 Enzalutamide (X... Placebo	18 Years -	Corcept Therapeutics

Spots Global Cancer Trial Database for antagonist

Every month we try and update this database with for antagonist 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.

Spots Global Cancer Trial Database for antagonist

Every month we try and update this database with for antagonist 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 antagonist 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.