Neoplasms

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Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

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Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma, Endometrioid

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

immunohistochemical, methylation, gene transfection

Torng Pao-Ling, MD, PhD

We have identified insulin-like growth factor binding protein (IGFBP)-3 as an invasion suppressor gene in ovarian endometrioid carcinoma, and showed association with lower cancer migration, invasion and metastasis. Recently, a novel model of ovarian EC formation from endometriosis was reported, and PTEN was found to be a major protein involved. Inactivation of PTEN has been reported in some ovarian EC tumors and methylation was suggested as one of the major epigenetic changes. This tumorigenesis model has lots of similarity to our established invasion model. Therefore, we plan to study the important of PTEN expression in ovarian EC and if inactivation of PTEN and IFGBP-3 is through methylation. Furthermore, by studying the signal transduction pathways using PTEN and IGFBP-3 transfection, we plan to study the mutual interaction between PTEN and IGFBP-3 on the suppression of tumor invasion in ovarian EC.

We have successfully established an ovarian cancer cell line (OVTW-59), which was derived from an ovarian endometrioid carcinoma (EC), and have also established an ovarian EC invasion model. By using cDNA microarray and quantitative reverse-transcriptase polymerase chain reaction, we identified insulin-like growth factor binding protein (IGFBP)-3 as an invasion suppressor gene, which were associated with lower cancer migration, invasion and metastasis. Clinically, lower IGFBP-3 was found associated with significantly higher tumor grade, advanced stage and poor survival in patients with EC tumors. Furthermore, we have proved IGFBP-3 expression correlated with lower Erk activation, but with no effect on the activation of Akt. All these two signal transduction proteins have crucial roles in cancer invasion. Recently, a novel model of ovarian EC formation from endometriosis was reported, and PTEN was found to be a major protein involved. Inactivation of PTEN has been reported in some ovarian EC tumors and methylation was suggested as one of the major epigenetic changes. This tumorigenesis model has lots of similarity to our established invasion model. Therefore, we plan to study the important of PTEN expression in ovarian EC and if inactivation of PTEN and IFGBP-3 is through methylation. Furthermore, by studying the signal transduction pathways using PTEN and IGFBP-3 transfection, we plan to study the mutual interaction between PTEN and IGFBP-3 on the suppression of tumor invasion in ovarian EC.

PTEN and IGFBP-3 Correlation in Ovarian Carcinoma Invasion

Correlation of PTEN and IGFBP-3 in the Invasion of Ovarian Endometrioid Carcinoma

National Taiwan University Hospital

Digestive System Diseases

Fallopian Tube Neoplasms

Peritoneal 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

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Fallopian Tube Diseases

Adenocarcinoma

Endometrial Neoplasms

Uterine Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Letrozole

Estrogens

Aromatase Inhibitors

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Letrozole, 2.5 mg Femara tablet, administered once daily for 5 years or until symptoms of toxicity or progression of underlying disease

Placebo tablet of Femara (without aromatase inhibitor), 0 mg Femara tablet, administered once daily for 5 years or progression of underlying disease

Letrozole 2.5mg

Placebo

Pamela McLaughlin, PhD

Maren Vogel, PhD

Ursula Sevelda, Dr. med.

Edgar Petru, Prof. Dr.

Christian Marth, Prof. Dr.

Cornelia Peternell, Dr med.

Barbara Spreitzer

Judith Lafleur, Dr. med.

Gerhard Bogner, PD. Dr. med.

Stephan Polterauer, Assoc. Prof. Priv. Doz. Dr.

Ursula Denison, Dr. med.

Petra Hnizdo

Radoslav Chekerov, PD Dr med

Klaus Pietzner, PD Dr med

Sara Tato-Varela, Dr. med.

Walter Kuhn, Prof.Dr.med.

Carolin Nestle-Krämling, Dr med

Eleni Tsepelidou, Dr med

Julia Welz, Dr. med.

Philipp Harter, Prof Dr med.

Alexander Hein, PD Dr med

Bettina Braun, Dr med

Maximillian Klar, Prof Dr med

Florin-Andrei Taran, Prof Dr med

Christoph Uleer, Dr med

Jasmin Pourfard, Dr med

Andreas Zorr, Dr med

Kristina Bätge, MD

Daniel Rein, Prof Dr med

Christin Traut, MD

Ralph Witteler, Dr med

Sebastian Schäfer, Dr med

Martina Gropp-Meier, Dr. med.

Thomas Decker, Prof Dr med.

Michael Weigel, Prof

Elke Wiegand, Dr. med.

Michael Eichbaum, Prof Dr med

Tatjana Cordes, Dr med

clemens Liebrich, Dr med

Vanessa Zahn, MD

Viola Heinzelmann-Schwarz, Prof

Dimitri Sarlos, PD

Maria Del Grande, Dr med,

Martin Heubner, Prof.

Thomas Schmid, Dr. med.

Julian Wampfler, Dr. med et phil

Ralf Rothmund, Prof.

Michael Schwitter, Dr. med.

Mathias Fehr, Prof.

Intidar Labidi-Galy, Dr. med.

Seraina Schmid, PD

Apostolos Sarivalasis, Dr. med.

Marcus Vetter, Dr. med.

Stefan Aebi, Prof.

Andreas Günthert, Prof

Christian Taverna, Dr. med.

René Hornung, Prof.

Andreas Müller, Dr. med.

Anita Hirschi-Blickenstorfer, Dr. med.

Natalie Gabriel, Dr. med.

Andreas Wicki, Porf.

Viola Heinzelmann-Schwarz, Prof. MD PhD

The purpose of this study is to evaluate the efficacy of addition of letrozole to the standard maintenance therapy in subjects following a primary diagnosis of Estrogen-receptor (ER) positive high and low grade epithelial ovarian cancer (including fallopian tube and primary peritoneal cancer) and subsequent primary treatment surgery and chemotherapy. Half of the participants will receive to the standard maintenance treatment, letrozole, whilst the other half receives placebo.

The study's primary hypothesis is that the treatment with letrozole increases progression free survival in comparison to the maintenance standard treatment (superiority trial).

Femara (letrozole) is an extensively investigated, marketed aromatase inhibitor (AI) widely used as treatment in the maintenance phase of estrogen-receptor (ER) positive breast cancer, as it inhibit the synthesis of estrogens. Estrogen is a well known driver of cancer growth in ER-positive tumors and a high percentage of the epithelial ovarian cancers express ER as well. Of which low grade ovarian cancers demonstrates the highest level of expression, supporting our strategy of a sub-group analysis (LOGOS). Therefore, letrozole in this study be investigated prospectively and evaluated as maintenance therapy after standard surgical and chemotherapy treatment in comparison to placebo (which is the current standard maintenance treatment) in subjects with primary, ER-positive low or high grade serous or endometrioid epithelial ovarian cancer (including fallopian tube and primary peritoneal cancer) of FIGO Stage II-IV, whose cancer has not progressed by the end of the platinum-based chemotherapy.

The objectives are to evaluate the letrozole maintenance treatment compared to placebo in terms of

* progression-free survival (PFS; primary endpoint)
* overall survival (OS)
* quality-adjusted progression free survival (QAPFS)
* time to first subsequent treatment (TFST)
* quality-adjusted time without symptoms of toxicity (Q-TWiST)
* health related quality of life (QoL) assessed by EQ-5D-5L, FACT-ES and FACT-O questionnaires

Methods: 540 for this study eligible subjects are 1:1 allocated in this randomized, controlled, double-blinded, multi-centre study to either the test (letrozole) or control (placebo) group. The maximum maintenance treatment duration is 5 years or until symptoms of toxicity or progression of underlying disease.

Health and health-related quality of life will continuously be assessed at study entry and during routine recalls which are scheduled every 12 weeks for the first 2 years, followed by every 24 weeks for the next 3 years. Procedures performed to assess the participants' health are the same as are performed during the regular routine ovarian cancer follow-up visits: blood tests, physical as well as gynaecological examinations and may include imaging. In addition, the participants are asked to complete during the study quality of life (QoL) specific questionnaires and wear an activity tracker for one week just before the scheduled visits. These assessments will be used for the evaluation of letrozole's efficacy and burden in comparison to the standard maintenance treatment. Survival follow-up data after the mainentance treatment duration of 5 years (study end) are obtained for up to another 7 years.

MAintenance Therapy With Aromatase Inhibitor in Epithelial Ovarian Cancer (MATAO)

MAintenance Therapy With Aromatase Inhibitor in Epithelial Ovarian Cancer: a Randomized Double-blinded Placebo-controlled Multi-centre Phase III Trial (ENGOT-ov54/Swiss-GO-2/MATAO), Including LOGOS (Low Grade Ovarian Cancer Sub-study).

PFS defined as the time from the date of first IMP administration until the date of progression (recurrence) or death by any cause in the absence of progression.

Assessment of progression (recurrence) is generally indicated by SYMPTOMS and will be assessed by the investigator most commonly on the basis of CT scans of the pelvis, abdomen and thorax, according to RECIST v1.1 criteria recommended and mostly presented by an elevated CA-125 level. Elevated CA-125 levels alone shouldn't be considered as progression. Progression assessment according to local standard of care, however, is similarly acceptable.

OS defined for each patient as the time from the date of first IMP administration until the date of death from any cause. Patients not having an event at the time of analysis will be censored at the date they were last known to be alive.

QAPFS defined as the time from the date of first IMP administration until the date of progression (recurrence) or death by any cause in the absence of progression under consideration of the quality of life during this period. QAPFS incorporates progression-free survival (quantity) and quality of life during this period into a measure of net clinical benefit:

QAPFS = PFS (years or months) x QoL (utility value).

Utility values derived from the EQ-5D-L5 questionnaire will be used.

TFST defined for each patient as the time from the date of first IMP administration until the date the patient started the next (second-line) subsequent anticancer treatment. Patients not receiving a subsequent anticancer treatment at the time of analysis will be censored at the date they were last known to be alive.

Q-TWiST defined as the Quality adjusted Time Without appearance of any Symptoms of Toxicity related to either the progression of the cancer or side effects of the trial medication from the date of first IMP administration until dead.

The Q-TWiST analysis considers the following three health states:

* (1) the period experiencing toxicity (TOX)
* (2) the period before progression without experiencing toxicity (TWiST)
* (3) the period after relapse (REL)

These periods are assigned preference utilities (u), which will be derived using the generic EQ-5D-5L questionnaire.

The Q-TWiST will be calculated as the weighted sum of the time spent in each health state:

Q-TWiST = uTox\*TOX + TWiST + uRel\*REL where u denotes the assigned utility for each respective health state.

Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) is included into the study to more specifically assess the side effects from the IMPs on quality of life. The minimum value is 0, the maximum value for the specific 19 item Endocrine Symptom Subscale (ESS-19) is 76. The higher the score, the better the QOL

In the context of this study the specific ovarian cancer symptom-oriented questionnaire Functional Assessment of Cancer Therapy - Ovarian (FACT-O) is included to assess the progression/recurrence of ovarian cancer on Quality of Life. The minimum value is 0, the maximum value including the specific Ovarian Cancer Subscale (OCS) is 152. The higher the score, the better the QOL

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
PTEN and IGFBP-3 Correlation in Ovarian Carcinoma Invasion	NCT00173407	Ovarian Cancer	immunohistochem...	21 Years - 80 Years	National Taiwan University Hospital
MAintenance Therapy With Aromatase Inhibitor in Epithelial Ovarian Cancer (MATAO)	NCT04111978	Ovarian Neoplas... Fallopian Tube ... Peritoneal Neop... High-grade Sero... Low-grade Serou... Ovarian Endomet...	Letrozole 2.5mg Placebo	18 Years -	Swiss GO Trial Group

Spots Global Cancer Trial Database for ovarian endometrioid carcinoma