Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Antineoplastic Agents

All Drugs and Chemicals

Etoposide

Etoposide phosphate

Cisplatine 20 mg/m² IV Etoposide 100 mg/m² IV Bléomycine 30 mg IV

chemotherapies protocols

Isabelle Ray-Coquard, Physician

To take charge of the treatment in rare adult ovarian tumors with an homogenous manner (germinal and sexual cords tumors), at different stages of the disease.

* to establish prognosis factors for the disease
* to proceed in a centralised examination of histologic laminas
* to reach in the long-term and homogenous follow-up of the patients
* to follow-up the long-term toxicities of the treatments given
* to analyse and follow-up the later fertility of the patients
* to evaluate the interest of setting a multi-disciplinary discussion forum on the Web

French Observatory of Rare Malignant Tumors of the Ovary

Observatoire Francophone Des Tumeurs Malignes Rares de l'Ovaire : Protocole de Prise en Charge Chez l'Adulte (Tumeurs Germinales et Des Cordons Sexuels)

ARCAGY/ GINECO GROUP

Symptoms and General Pathology

Recurrence

Fallopian Tube Neoplasms

Fallopian Tube Diseases

Fallopian Tube Cancer

Paclitaxel

Albumin-Bound Paclitaxel

Taxane

Tubulin Modulators

Antimitotic Agents

Part 1 of the study will determine the safety of continuous twice a day oral dosing of GRN-300, with each cycle consisting of 28 days of treatment. The number of administered cycles will depend on the tolerability of each dose level and the severity and occurrence of side effects and DLTs. The maximal tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of GRN-300 as a single agent will be determined. The overall duration of Part 1 will be approximately 24-36 months, depending on the rate of enrollment and the number of subjects enrolled.

The study will determine the safety of continuous twice a day oral dosing of GRN-300, with each cycle consisting of 28 days of treatment, in combination with intravenously administered paclitaxel weekly x 3 during each 28-day cycle. The number of administered cycles will depend on the tolerability of each dose level and the severity and occurrence of side effects and DLTs. The maximal tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of GRN-300 in combination with paclitaxel will be determined. The overall duration of Part 2 will be approximately 12-18 months, depending on the rate of enrollment and the number of subjects enrolled. Part 2 will commence following determination of the MTD and RP2D of single-agent GRN-300 in Part 1.

Overall duration of the study will be approximately 36-48 months, depending on the rate of enrollment and number of subjects enrolled.

GRN-300

Siqing Fu, MD, PhD

The study consists of two parts based on the administration of single-agent GRN-300 or in combination with paclitaxel.

Part 1 (Phase IA) will test the tolerability of continuous twice a day dosing of oral GRN-300, a salt-inducible kinase inhibitor, with each cycle consisting of 28 days of treatment. The number of administered cycles will depend on the tolerability of each dose level and the severity and occurrence of dose limiting toxicities (DLTs) or adverse events.

Part 2 (Phase IB) will test the tolerability of continuous 28-day cycles of GRN-300 in combination with weekly paclitaxel given 3 of 4 weeks per month (x 3).

Overall duration of the study will be approximately 48 months, depending on the rate of enrollment and number of subjects enrolled.

Part 1: Phase 1A

Primary objectives:

Determination of the maximum tolerated dose (MTD), if applicable, and recommended Phase II dose (RP2D) of GRN-300 in the study population.

To investigate the safety and tolerability of repeated 28-day cycles of oral GRN-300 therapy in subjects with persistent or recurrent, locally non-resectable or metastatic ovarian, fallopian tube, and primary peritoneal cancer or other advanced solid tumors.

Secondary objectives:

To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.

To estimate the clinical activity of GRN-300 monotherapy by determining the following:

* Overall response rate (ORR) per investigator assessment using RECIST v1.1 defined as the percentage of subjects having a best overall response (BOR) of complete response (CR) or partial response (PR)
* Disease control rate (DCR) per investigator assessment using RECIST v1.1 defined as the percentage of subjects having a BOR of CR, PR, or stable disease (SD) ≥ 4 months (4 cycles, 28 days each).

Part 2: Phase 1B

Primary objectives:

Determination of the RP2D of GRN-300 in combination with weekly paclitaxel given 3 of 4 weeks per month (x 3) in the study population.

To investigate the safety and tolerability of repeated 28-day cycles of daily oral GRN-300 therapy in combination with weekly paclitaxel x 3 in subjects with persistent or recurrent, locally non-resectable or metastatic, ovarian, fallopian tube, and primary peritoneal cancer, where treatment with paclitaxel is appropriate.

Secondary objectives:

To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.

To estimate the clinical activity of GRN-300 in combination with paclitaxel by determining the following:

* Overall response rate (ORR) per investigator assessment using RECIST v1.1 defined as the percentage of subjects having a best overall response (BOR) of complete response (CR) or partial response (PR)
* DCR per investigator assessment using RECIST v.1.1 defined as the percentage of subjects having a BOR of CR, PR, or SD ≥ 4 months (4 cycles, 28 days each).

Exploratory Translational Objectives for Both Study Parts:

* To estimate progression free survival (PFS) per investigator assessment using RECIST v1.1 for subjects who received continuous GRN-300 and weekly paclitaxel x 3.
* Evaluate exploratory biomarkers of target engagement and treatment response

GRN-300 single-agent and in combination with paclitaxel.

First-in-Human Evaluation of GRN-300 in Subjects With Recurrent Ovarian, Primary Peritoneal, and Fallopian Tube Cancers.

Ph 1/1B Evaluation of the Safety, Pharmacokinetics and Efficacy of GRN-300, a Salt-inducible Kinase Inhibitor, Alone and in Combination With Paclitaxel, in Recurrent Ovarian, Primary Peritoneal, and Fallopian Tube Cancers.

• To estimate progression free survival (PFS) per investigator assessment using RECIST v1.1 for subjects who received continuous GRN-300 single-agent or in combination with weekly paclitaxel x 3

• Determination of the recommended Phase II dose (RP2D) of GRN-300 in the study population.

• To investigate the safety of repeated 28-day cycles of daily oral GRN-300 therapy in subjects with recurrent or metastatic ovarian, fallopian tube, and primary peritoneal cancer or other advanced solid tumors, based on the number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

• Determination of the recommended Phase II dose (RP2D) of GRN-300 in combination with weekly paclitaxel in the study population.

• To investigate the safety of repeated 28-day cycles of daily oral GRN-300 therapy in combination with weekly paclitaxel x 3 in subjects with recurrent or metastatic ovarian, fallopian tube, and primary peritoneal cancer or other advanced solid tumors, based on the number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

• To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.

- Maximum plasma concentration (Cmax)

• To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.

- Time to Cmax (tmax)

• To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.

- Terminal half-life (t1/2)

• To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.

- Area under the plasma concentration-time curve from zero to the last measurable concentration (AUC0-t)

• To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.

- Area under the plasma concentration-time curve from zero to infinity (AUC0-Inf)

• To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.

- Apparent oral clearance (CL/F)

• To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.

- Apparent volume of distribution during terminal distribution phase (Vz/F)

• Overall response rate (ORR) per investigator assessment using RECIST v1.1 defined as the percentage of subjects having a best overall response (BOR) of complete response (CR) or partial response (PR)

• Disease control rate (DCR) per investigator assessment using RECIST v1.1 defined as the percentage of subjects having a BOR of CR, PR, or stable disease (SD) ≥ 4 months (4 cycles, 28 days each)

• To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.

- Maximum plasma concentration (Cmax)

• To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.

- Time to Cmax (tmax)

• To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.

- Terminal half-life (t1/2)

• To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.

- Area under the plasma concentration-time curve from zero to the last measurable concentration (AUC0-t)

• To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.

- Area under the plasma concentration time curve from zero to infinity (AUC0-Inf)

• To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.

- Apparent oral clearance (CL/F)

• To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.

- Apparent volume of distribution during terminal distribution phase (Vz/F)

• DCR per investigator assessment using RECIST v.1.1 defined as the percentage of subjects having a BOR of CR, PR, or SD ≥ 4 months (4 cycles, 28 days each)

Green3Bio, Inc.

Cysts

Ovarian Cysts

Standardized transvaginal ultrasound examination

Dirk Timmerman, MD, PhD

Wouter Froyman, MD

Dirk Timmerman, PhD

Tom Bourne, MD, PhD

Ben Van Calster, MSc, PhD

Ignace Vergote, MD, PhD

Lil Valentin, MD, PhD

Antonia C Testa, MD, PhD

Sabine Van Huffel, MSc, PhD

The ability of different methods to discriminate between benign and malignant adnexal masses has been compared in a meta-analysis showing that the IOTA Simple Rules and the IOTA logistic regression model LR2 were superior to RMI and to all other methods for predicting malignancy in an adnexal mass included in the meta-analysis. However, a fair comparison of methods requires them to be applied on the same tumor population.

The general objective of this study is to prospectively validate the Simple Rules, ADNEX, the Simple Rules risk model, LR2, and RMI on a large multicenter dataset to allow direct comparison of these tools.

IOTA7 is an international multicenter prospective observational study including different types of ultrasound centers and examiners with different levels of ultrasound experience. In total, about 1700 adnexal masses with histological outcome will be included in IOTA 7.

Ovarian cancer is a common and lethal disease for which early detection and treatment in high volume centers and by specialized clinicians is known to improve survival. Hence, accurate methods to preoperatively characterize the nature of an ovarian tumor are pivotal.

The best ultrasound method for discrimination between benign and malignant adnexal masses is subjective assessment, i.e. subjective evaluation of ultrasound findings. Subjective assessment, however, requires a very experienced ultrasound examiner. More objective methods may be preferred by less experienced examiners who are not confident with using subjective assessment. The Risk of Malignancy Index (RMI) is one such method. There are also more recently developed methods. The International Ovarian Tumor Analysis (IOTA) group have created logistic regression models (LR1, LR2, and the ADNEX model) including clinical and ultrasound information to calculate the likelihood of malignancy in adnexal masses.

The IOTA group has also suggested simple ultrasound rules that can be used to classify adnexal masses as benign or malignant.

The ability of different methods to discriminate between benign and malignant adnexal masses has been compared in a meta-analysis showing that the IOTA Simple Rules and the IOTA logistic regression model LR2 were superior to RMI and to all other methods for predicting malignancy in an adnexal mass included in the meta-analysis. However, a fair comparison of methods requires them to be applied on the same tumor population.

The general objective of this study is to prospectively validate the Simple Rules, ADNEX, the Simple Rules risk model, LR2, and RMI on a large multicenter dataset to allow direct comparison of these tools. The patients will be examined by operators of varying levels of experience, such that the investigators can study how experience might affect diagnostic performance.

IOTA7 is an international multicenter prospective observational study including different types of ultrasound centers and examiners with different levels of ultrasound experience. In total, about 1700 adnexal masses with histological outcome will be included in IOTA 7.

Patients with a known or suspected adnexal mass examined with transvaginal (or transrectal if vaginal is not possible) ultrasound by an IOTA certified ultrasound examiner and confirmed to have an adnexal mass judged not to be physiological but likely to undergo surgery (primarily planned for surgical management based on subjective assessment by the ultrasound investigator) will be recruited consecutively Upon inclusion in the study, an oral or written (depending on the requirements of the local Ethics Committee) informed consent is obtained from the patient.

Data collection is done through the web-based clinical data miner (CDM) software. Data are stored on a secure server.

First, clinical information about the patient is entered into CDM. Second, the ultrasound examiner provides a diagnosis based on subjective assessment, and notes the suggested management. Third, detailed ultrasound information needed for the different models to be validated is entered. When these data have been frozen (so they can no longer be changed) the examiner gets access to the results of the Simple Rules and ADNEX. The ultrasound examiner then records whether these results make him/her change the management suggested on the basis of subjective assessment. If so the new management is specified.

Gold standard for validation of discriminative ability and calibration is the histology of the adnexal mass within 180 days after the ultrasound examination following surgical removal by laparotomy or laparoscopy as considered appropriate by the surgeon. In case of malignancy, the stage of the malignant tumors using the classification of the International Federation of Gynecology and Obstetrics (FIGO) is noted.

Prospective Validation and Comparison of Different Ultrasound Methods for Discrimination Between Benign and Malignant Ovarian/Tubal Masses Prior to Surgery

Prospective Validation and Comparison of Subjective Assessment, the International Ovarian Tumor Analysis (IOTA) ADNEX Model, Logistic Regression Model LR2, Simple Rules and the Risk of Malignancy Index (RMI) for Discrimination Between Benign and Malignant Adnexal Masses in the Hands of Ultrasound Examiners With Different Levels of Experience

KU Leuven

Prof. Dr.

The purpose of this study is to learn more about the appearance and behavior of benign-looking adnexal masses.

* Benign-looking means that when viewed here by ultrasound it has the appearance of looking not harmful or not malignant.
* Adnexal refers to the 'adnexa', the space in the female pelvis on either side of the uterus (or where the uterus used to be if you previously had a hysterectomy). The adnexa includes, but is not limited to, the ovaries and the fallopian tubes.
* Masses refers to a variety of structures, including but not limited to:

  * ovarian cysts that are fluid filled sacs within or attached to an ovary
  * ovarian tumors that can be solid tissue or a combination of cysts and solid tissue
  * hydrosalpinges that are fluid collections in the fallopian tube

Many women have what appear to be benign adnexal masses. Many times, removal of the masses with surgery is not necessary. Often surgery is performed unnecessarily, for fear that these masses could be cancer. There is not much information available for doctors to know how and when to follow these masses, or which ones will become cancer.

This study will combine information from centers all around the world regarding the behavior of all types of benign adnexal masses. The aim of this study is to develop decision tools for doctors to know the best way to treat these masses in order to improve the detection of ovarian cancer while at the same time reduce the number of unnecessary operations.

International Ovarian Tumour Analysis (IOTA) Phase 5

A Multicentre Study to Examine the Short and Long Term Outcomes of the Conservative Management of Benign-looking Adnexal Masses and the Pre-operative Characterisation of Ovarian Tumours

Also to establish descriptive curves of the longitudinal changes seen in parameters from conservatively managed benign tumors (for example, change in diameter, size of any solid component, number of papillations or color score)

Also to predict complications (e.g. occurrence of malignancy and other) during long-term follow-up using the diagnostic models

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
French Observatory of Rare Malignant Tumors of the Ovary	NCT01304043	Ovarian Tumors	chemotherapies ...	18 Years -	ARCAGY/ GINECO GROUP
French Observatory of Rare Malignant Tumors of the Ovary	NCT01304043	Ovarian Tumors	chemotherapies ...	18 Years -	ARCAGY/ GINECO GROUP
First-in-Human Evaluation of GRN-300 in Subjects With Recurrent Ovarian, Primary Peritoneal, and Fallopian Tube Cancers.	NCT04711161	Ovarian Tumors	GRN-300 Paclitaxel	18 Years -	Green3Bio, Inc.
Prospective Validation and Comparison of Different Ultrasound Methods for Discrimination Between Benign and Malignant Ovarian/Tubal Masses Prior to Surgery	NCT02847832	Patients With A...	Standardized tr...	-	KU Leuven
First-in-Human Evaluation of GRN-300 in Subjects With Recurrent Ovarian, Primary Peritoneal, and Fallopian Tube Cancers.	NCT04711161	Ovarian Tumors	GRN-300 Paclitaxel	18 Years -	Green3Bio, Inc.
International Ovarian Tumour Analysis (IOTA) Phase 5	NCT01698632	Adnexal Masses Ovarian Cysts Ovarian Tumors		18 Years -	KU Leuven

Spots Global Cancer Trial Database for ovarian tumors