A study to look at the effects of different treatments on rare types of previously treated epithelial ovarian, fallopian tube or primary peritoneal cancers with different molecular changes

1. Why is this study needed?

Cancer is a health condition where the body's cells start growing and multiplying in an uncontrolled and abnormal way. These cells don’t follow the usual pattern of cell division and growth. Instead they form a lump or mass called a tumour. Some cancers have certain changes in their genes. Genes are a sections of DNA that has instructions for making the body. These changes help the cancer grow and survive. New treatments may work better than current ones by targeting changes in cancer.

This study is testing different anti-cancer medicines. They are being developed to treat rare epithelial ovarian, fallopian tube or primary peritoneal cancers (rare EOC). Some of the anti-cancer medicines in this study are approved by authorities (like the U.S. Food and Drug Administration and European Medicines Agency). They are approved on their own or with other medicines for treating certain cancers in some countries. In this study, the anti-cancer medicines or medicine combinations are experimental. This means health authorities have not approved them for treating rare EOC. This study aims to test the effects of different anti-cancer medicines in people with rare EOC with certain changes in the genes.

2. Who can take part in the study?

Females of 18 years of age or older with certain types of rare EOC can take part in the study. But only if they have previously received treatment, including at least one platinum-based treatment. They must also meet other criteria for the group they join.

People may not be able to take part in this study if they have fast-growing (high-grade serous or high-grade endometrioid) EOC. Neither can people who have previously received certain medications or have certain medical conditions. People who are pregnant, or currently breastfeeding cannot take part in the study.

3. How does this study work?

Participants will be screened to check if they are able to participate in the study. The screening period will take place from 1 day to 1 month before the start of treatment. Study medicines will be given in ‘cycles’. A treatment cycle is the period of treatment and recovery time before the next set of treatment is given.

Everyone in this study will join 1 of 11 groups. The group a participant is put into will depend on the type of cancer they have AND if they meet the criteria to join that group. Participants will be given either:

• Group A: ipatasertib, given as a pill to be swallowed on Days 1 to 21 of each 4-week cycle AND paclitaxel as a drip into a vein on Days 1, 8 and 15 of each 4-week cycle
• Group B: cobimetinib, given as a pill to be swallowed on Days 1 to 21 of each 4-week cycle
• Group C: trastuzumab emtansine, given as a drip into a vein every 3 weeks
• Group D: atezolizumab AND bevacizumab, given as drips into a vein every 3 weeks
• Group E: giredestrant, given as a pill to be swallowed once a day AND abemaciclib given as a pill to be swallowed twice a day
• Group F: inavolisib, given as a pill to be swallowed once a day AND palbociclib, given as a pill to be swallowed on Days 1 to 21 of each 4-week cycle
• Group G: inavolisib AND letrozole, given as pills to be swallowed once a day, AND palbociclib, given as a pill to be swallowed on Days 1 to 21 of each 4-week cycle
• Group H: inavolisib, given as a pill to be swallowed once a day, AND olaparib given as a pill to be swallowed twice a day
• Group I: inavolisib AND giredestrant, given as pills to be swallowed once a day
• Group J: inavolisib, given as a pill to be swallowed once a day AND bevacizumab, given as a drip into a vein every 3 weeks
• Group K: atezolizumab AND bevacizumab, given as drips into a vein every 3 weeks, AND cyclophosphamide given as a pill to be swallowed once a day

This is an open-label study. This means everyone involved, including the participant and the study doctor, will know the study treatment the participant has been given.

During this study, the study doctor will see participants regularly. They will see how well the treatment is working and any unwanted effects participants may have. Participants will have follow-up visits either at a clinic or by telephone calls around every 3 months after completing the study treatment, for as long as they agree to it. The follow-up visits are done to check on the participant’s wellbeing and to see if they have received any other treatments since completing study treatment. Total time of participation in the study could be more than 2 years, depending on how the participant responds to the study treatment. Participants have the right to stop study treatment and leave the study at any time, if they wish to do so.

4. What are the main results measured in this study?

The main result measured in the study to assess if the medicines have worked is how many participants have a specific level of reduction in the size of their tumour. Other key results measured in the study include:

• How much time is there between the participant’s cancer first responding to treatment and the cancer getting worse
• The time between when a participant has no signs of cancer and when the cancer worsens
• How long participants live without their cancer getting worse
• The number of participants who are alive and whose cancer has not gotten worse 6 months after starting treatment
• How long participants live
• The number and seriousness of unwanted effects

5. Are there any risks or benefits in taking part in this study?

Taking part in the study may or may not make participants feel better. But the information collected in the study can help other people with similar health conditions in the future.

It may not be fully known at the time of the study how safe and how well the study treatment works. The study involves some risks to the participant. But these risks are generally not greater than those related to routine medical care or the natural progression of the health condition. People interested in taking part will be informed about the risks and benefits, as well as any additional procedures or tests they may need to undergo. All details of the study will be described in an informed consent document. This includes information about possible effects and other options of treatment.

Risks associated with the study medicines

Participants may have unwanted effects of the medicines used in this study. These unwanted effects can be mild to severe, even life-threatening, and vary from person to person. During this study, participants will have regular check-ups to see if there are any unwanted effects.

Participants will be told about the known unwanted effects of the study medicines, and possible unwanted effects based on human and laboratory studies or knowledge of similar medicines. Known unwanted effects include cough, rash, fever, frequent watery stools, throwing up or wanting to throw up, feeling tired or weak, and pain or discomfort in the head. The study medicines ipatasertib, cobimetinib, giredestrant, abemaciclib, inavolisib, palbociclib, letrozole, olaparib and cyclophosphamide will be given as a pill to be swallowed. The study medicines paclitaxel, trastuzumab emtansine, bevacizumab, atezolizumab will be given as drips into a vein. Known unwanted effects of a drip into a vein include itching, feeling or being sick, a feeling of coldness that makes the body shiver, low blood pressure, fever, reddening of the skin, pain or discomfort in the head, a rapid heart rate, breathing problems, throat irritation, pain or swelling.

The study medicine(s) may be harmful to an unborn baby. Women and men must take precautions to avoid exposing an unborn baby to the study treatment.

For more information about this clinical trial see the For Expert tab on the specific ForPatient page or follow this link to ClinicalTrials.gov

Trial-identifier: NCT04931342