This non-interventional observational study aims to investigate the long-term treatment with niraparib in patients with platinum-sensitive ovarian cancer who have been diagnosed for the first time or have already suffered a relapse (recurrence) and to identify factors associated with long-term survival. Niraparib is a so-called PARP inhibitor that prolongs the effect of chemotherapy after its completion by suppressing the repair mechanisms in the cancer cells damaged by the chemotherapy. The damaged cells are then unable to regenerate and die.

What is the aim of the study?

The aim is to find out which typical features/characteristics with regard to the disease, therapy and patients are associated with long-term survival. The study will also investigate which treatment-specific factors of niraparib administration (dose, side effects, duration of therapy, quality of life during therapy) correlate with long-term survival.

What is the procedure for the study?

This is an observational study in which the decision to treat with niraparib was made by the doctor and patient before the start of the study and the therapy is carried out according to the standard regimen. Patient data is collected at the beginning of the study and every six months thereafter, for up to eight years after study inclusion.

Are there any risks?

This is a purely observational study, i.e. the patients do not receive any additional medication or other treatment regimes. In this respect, the study participants are not exposed to any additional risks or side effects. However, treatment with niraparib, which is prescribed to patients with ovarian cancer after chemotherapy in the relapse situation, can have side effects, e.g. lead to a lack of blood platelets, a lack of certain white blood cells (neutrophil granulocytes), anemia, high blood pressure or fatique syndrome.

Participation requirements

Women aged 18 and over with ovarian, fallopian tube or peritoneal cancer who have been diagnosed for the first time or have relapsed (confirmed by histological findings) and who have achieved a tumor response with chemotherapy can take part in this study. Patients must be suitable for maintenance therapy with niraparib, i.e. they must have no contraindications and be able to take oral medication independently and reliably. Patients who are hypersensitive to the preparation, pregnant or breastfeeding may not take part in the study.

Where can I take part in the study?

This study is supported by:

The research-based pharmaceutical company GLAXOSMITHKLINE is a partner in this study.

What is being investigated in this study?

Ovarian cancer is often difficult to treat, especially if it recurs after chemotherapy with platinum-based drugs (e.g. carboplatin) or has become insensitive to this treatment. Such cases are referred to as platinum-resistant ovarian cancer.

Researchers have discovered that a specific protein – claudin-6 (CLDN6) – is present in large quantities in many of these tumors. This protein is normally only present in very early stages of cell development and is rarely found in healthy tissue. CLDN6 is therefore considered a promising target for specifically attacking tumor cells without severely damaging healthy tissue.

TORL-1-23 is a so-called antibody-drug conjugate (ADC). This means that this drug consists of an antibody that specifically recognizes and binds CLDN6 proteins on the tumour cell. An active substance is coupled to the antibody, which is introduced into the tumor cell and can destroy the cancer cell there.

An earlier phase 1 trial has already shown that TORL-1-23 was well tolerated and can be active against tumors with CLDN6 expression. The CATALINA-2 trial is now investigating how effective and safe the drug is in a larger group of patients.

What is the aim of the study?

The main aim of the study is to find out how well TORL-1-23 as the sole therapy (monotherapy) delays the progression of the disease and how long patients benefit from the treatment.
In addition, the study will investigate which dosage works best and is also well tolerated.

What is the survey procedure?

The CATALINA-2 study consists of two sections:

• Part 1 (Dose finding):
  This section examines which dose of TORL-1-23 shows the best combination of efficacy and tolerability. For this purpose, doses in three different arms are examined (allocation to one of the arms is randomized):

Arm 1: 2.4 mg TORL-1-23
Arm 2: 3.0 mg TORL-1-23
Arm 3: 3.4 mg TORL-1-23

• Part 2 (efficacy testing):
  TORL-1-23 is tested in a larger group of patients with the dosage determined in Part 1.

Are there any risks?

You will be informed about possible risks and side effects associated with participation during an information session.

Participation requirements

Women aged 18 and over can take part in this study, with:

• Diagnosis of advanced or metastatic, high grade ovarian, fallopian tube or primary peritoneal cancer not responding to platinum-based therapies
• Proven formation of claudin-6 on the surface of the tumor (central laboratory test as part of the study)
• Proven presence of residual tumor at study entry

However, there are also other criteria that must be met in order to participate in the study. Interested patients should speak to the investigators at a study center, who can check whether this study is suitable for them.

The HELP-ER study was designed to improve the treatment of patients with a first relapse of platinum-sensitive ovarian cancer. In the first phase (Part A), patient data from a database is analyzed in order to develop an algorithm that predicts the outcome of surgery using biomarkers. In the second phase (Part B), this algorithm will be tested in a new group of patients. The aim is to make the treatment more targeted and successful. The study is purely observational, with no intervention in the treatment.

What is being investigated in this study?

The idea for this study is based on the fact that there is no clear standard for the treatment of relapse in ovarian cancer. Relapses are often treated with either chemotherapy or surgery. New studies show that complete removal of the tumor in case of recurrence can prolong survival. During these studies, the AGO score was also developed and validated. This score is used to predict the surgical removability of the tumor. However, not all patients benefit equally from surgery, which is why it makes sense to expand the score to include other influencing factors.

HE4 (Human Epididymis Protein 4) is a protein that can be measured in the blood. It is often highly expressed in ovarian cancer and could help to better plan treatment. The study is therefore investigating whether certain biomarkers such as HE4 can help predict who might benefit from surgery.

What is the aim of the study?

The aim of the HELP-ER study is to improve the AGO score by including additional biomarkers such as HE4 and CA125 in the assessment. The AGO score is a tool that helps doctors to assess whether complete tumor removal by surgery is likely in the event of a recurrence of ovarian cancer.

The addition of biomarkers could increase predictive accuracy, as they provide additional information on tumor status and disease activity. The aim is to avoid unnecessary operations and better adapt treatments to individual patients.

What is the procedure for the study?

The HELP-ER observational study is divided into two stages:

1. retrospective analysis

Data from 188 patients from the Tumor Bank Ovarian Cancer (TOC) network who have already had a second tumor removal (debulking surgery) for a recurrence will be analyzed. Clinical information and biomarker values are then combined to develop an algorithm to predict how successful a repeat operation might be. The AGO score serves as the basis for this analysis.

2. prospective testing of the algorithm

497 patients with a platinum-sensitive relapse are divided into two groups (cohorts) (as decided by the treating physicians):

• Cohort 1: receives conservative treatment or “wait-and-see strategy”
• Cohort 2: undergoing surgery

It is expected that at least 164 of the 497 patients (33%) will undergo a repeat operation. In approximately 131 of the operated patients (around 80 %), the tumor will be completely removed in order to validate the predictions of the algorithm.

Are there any risks?

This is a purely observational study, i.e. the patients do not receive any additional medication or other treatment regimes. In this respect, the study participants are not exposed to any additional risks or side effects. You will be informed about possible risks and side effects associated with participation during an information session.

Conditions of participation

Women aged 18 and over can take part in this study, with:

• Recurrent ovarian cancer of epithelial origin
• Consent to the examination of previously taken tumor samples
• Existing blood sample taken before the operation

What is the aim of the study?

This trial is investigating a new combination treatment for women with low-grade serous ovarian cancer that has returned after previous treatment. The aim is to determine whether this new treatment works better than current standard treatments. Current treatments for LGSOC, such as chemotherapy and hormone therapy, may not always be as effective as desired. For this reason, this study is looking at a new combination of investigational drugs, avutometinib and defactinib, to see if they are better at slowing or stopping cancer growth in patients with LGSOC. Both drugs are kinase inhibitors – drugs that target specific signaling pathways that cancer cells use to grow.

What is the survey procedure?

If the study is suitable for you and you decide to participate:

you will be randomly assigned to either the new combination treatment being studied or one of several standard treatments chosen by your doctor.

Group 1: You will receive avutometinib twice a week and defactinib twice a day in tablet form. These drugs are taken for three weeks, followed by a one-week break, which together form a cycle.

Group 2: Standard care for LGSOC. One of the currently available treatments, such as chemotherapy or hormone therapy, based on your doctor’s recommendation.

You will undergo regular examinations, scans and blood tests to monitor your health and your cancer. The length of your participation will depend on how your body responds to the treatment. You will continue to receive the study treatment for as long as it helps to control your cancer and you can tolerate any side effects.

If you are assigned to Group 2 and your cancer worsens during treatment, you may be eligible for cross-over to Group 1. Even after your treatment has ended, you will be followed up for up to 5 years to monitor your health.

Are there any risks?

The new treatment may cause side effects, some of which may be serious, e.g. skin reactions, digestive problems, eye problems.
The new treatment may not work as well as the standard treatments. You may be assigned to a standard treatment instead of the new treatment.

Participation requirements

The study could be suitable for you if you:

• are at least 18 years old
• have been diagnosed with recurrent low-grade serous ovarian cancer
• have measurable tumors on scans
• are physically fit enough to participate in a clinical trial
• are willing to undergo regular medical examinations, blood tests and other health assessments

STUDY FOR PATIENTS WITH RECURRENT OR RELAPSED OVARIAN CANCER

The FraStROC study is a non-interventional, prospective, multicenter observational study in which the frailty and fragility of ovarian cancer patients in the recurrence situation during chemotherapy is evaluated. The study is being conducted in two phases.

What is the aim of the study?
The aim of the study is to prospectively evaluate inflammatory markers, organ dysfunction, functional tests and geriatric assessment measures and patient-reported outcome for their ability to predict hematologic toxicity or non-hematologic toxicity.

What is the procedure for the study?
This is a prospective, multicenter, non-interventional, observational study in 2 stages for patients with epithelial ovarian cancer or carcinosarcoma (EOC), fallopian tube cancer (FTC) or primary peritoneal cancer (PPC) who require monotherapy for recurrent disease and have participated in at least one prior systemic treatment.

Steps 1 and 2:
In the study, demographic, clinical and pathological aspects of the patients are assessed, the measures taken before the start of chemotherapy are documented and an assessment of toxicity is carried out for one year from the start of treatment (follow-up).
In the first step of the study, a frailty score is to be determined on the basis of the data collected in order to estimate the probability that chemotherapy will have to be discontinued due to side effects. In the second step of the study, the calculated score will be tested (validated).

Are there any risks?
No, it is an observational study.

PARTICIPATION REQUIREMENTS

Can I take part in this study?
Most important inclusion and exclusion criteria:

Patients must submit a written declaration of consent in advance and be at least 18 years old:

• have a histologically confirmed diagnosis of epithelial ovarian cancer, carcinosarcoma, primary peritoneal cancer or fallopian tube cancer
• have a recurring cancer
• are eligible for monochemotherapy with paclitaxel, doxorubicin (PLD), topotecan or treosulfan with optional use of bevacizumab
• have received at least one previous treatment regimen for ovarian cancer (permitted from the second line of treatment)
• have a life expectancy of at least 12 weeks.

Ineligible patients:
Patients are excluded if:

• they are only eligible for combination chemotherapy or maintenance therapy after previous chemotherapy or radiotherapy is planned.

In addition, there are further criteria that must be met. Interested patients should speak to an investigator at a study center who can check whether they are eligible for this study.