Study to Evaluate the Efficacy and Safety of CYH33 in Patient with Recurrent/Persistent Ovary, Fallopian Tube or Primary Peritoneal Clear Cell Carcinoma

JRCT ID: jRCT2031210216

Registered date:30/07/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Target indication: in Patients with Recurrent/Persistent Ovary, Fallopian Tube or Primary Peritoneal
• Date of first enrollment: 01/09/2021
• Target sample size: 36
• Countries of recruitment: China,Japan,USA,Japan
• Study type: Interventional
• Intervention(s): CYH33 will be administered orally continuous once daily in 21-day treatment cycles until disease progression, unacceptable AE or withdrawal of consent. There are no breaks in dosing between cycles. Patients should follow the instructions of the treating physician on study drug administration during treatment. Patients are required to fast for at least 2 hours before and 1 hour after administration of CYH33. Patients will be permitted to drink water during this period. If a patient misses a dose (i.e., did not take CYH33 for > 10 hours of the scheduled time of the day), the patient should take the dose on the next day.

Outcome(s)

• Primary Outcome: To determine the efficacy of single agent CYH33 in patients with recurrent or persistent ovarian, fallopian tube or primary peritoneal clear cell carcinoma harboring PIK3CA hotspot mutations using objective response rate (ORR) by Blinded Independent Review Committee (BIRC) assessment.

Secondary Outcome

- To evaluate treatment benefit of CYH33 with respect to ORR by BIRC assessment for patients without PIK3CA hotspot mutations.
- To evaluate the efficacy of CYH33 with respect to progression-free survival (PFS), 6-month PFS rate, duration of response (DoR), time to response (TTR) and disease control rate (DCR) by BIRC in each of the PIK3CA mutation status cohort.
- To evaluate the efficacy of CYH33 with respect to ORR, PFS, 6-month PFS rate, DoR, TTR and DCR by investigator in each of the PIK3CA mutation status cohort.
- To evaluate overall survival (OS) benefit in each of the PIK3CA mutation status cohort.
- To assess the PIK3CA mutation status, and to explore the relationship between biomarker alteration status and efficacy in the study population.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Female

Include criteria

This Global Phase II trial is for recurrent/persistent clear cell carcinoma of the ovary, fallopian tube, and primary peritoneum, with the following PIK3CA hotspot mutations.
E542K, E542A, E542Q, E542V, E545A, E545D, E545G, E545K, Q546E, Q546R, Q546K, Q546P, Q546H, H1047L, H1047R, H1047Y, H1047Q

1. You fully understand the contents of this informed consent document. You can provide voluntarily consent by signing the informed consent form by yourself.
2. You are a female patient = > 18 years of age (or having reached the age of maturity according to local laws and regulations)
3. You must have histologically or cytologically confirmed recurrent or persistent ovarian, fallopian tube or peritoneum clear cell carcinoma. The tumors should be negative for expression of WT-1 antigen and Estrogen Receptor (ER) antigen by immunohistochemistry (IHC). To participate in this study, you must have at least one measurable lesion as per RECIST 1.1.
4. You must be able to provide a tissue sample of your tumor in order to identified PIK3CA gene mutation status (with or without PIK3CA hotspot mutations): For safety run-in, you are eligible regardless of your PIK3CA gene mutation status. If your PIK3CA gene mutation status has been determined, the pre-existing test result should be submitted for documentation. If your PIK3CA gene mutation status is unknown, you can still be enrolled, and a PIK3CA status testing is required after enrollment upon sample availability. In global phase II study, only patients with PIK3CA hotspot mutation can be enrolled. The patients can participate in the clinical screening procedures for the main study on the basis of a pre-existing known PIK3CA hotspot mutation, and tumor tissue sample should be collected for a confirmatory detection of PIK3CA mutational status by a Sponsor Designated Central Laboratory. For patients whose PIK3CA mutation status is unknown, a tumor tissue for the PIK3CA test must be taken to a Sponsor Designated Central Laboratory and the result report must be available prior to clinical screening procedures for the main study.
5. You must have failed first-line standard chemotherapy (Neo-adjuvant therapy will not count as first-line therapy) and no more than three prior lines of systemic therapy (In safety run-in part, patients who have received more than three prior lines of systemic therapy are also eligible, but the ECOG-PS should be 0).
(Note: Treatment failure is defined as documented disease progression.)
6. You must have adequate organ and bone marrow function measured within 28 days of screening.
7. Eastern Cooperative Oncology Group performance status (ECOG-PS) = < 1.

Exclude criteria

1. You have received any anticancer therapy (including chemotherapy, targeted therapy, hormonal therapy, biotherapy, immunotherapy, or other investigational agents.) within 28 days or 5 times of half-lives (whichever is shorter) prior to the first dose of the study drug.
2. You had prior treatment with any PI3K, mTOR or AKT inhibitor.
3. You have received radical radiation therapy (including radiation therapy for over 25% bone marrow) within 28 days prior to the first dose of the study drug or received local palliative radiation therapy for bone metastases within 2 weeks.
4. You currently have any toxicities (side effects) from prior treatment that have not recovered to baseline or CTCAE Grade 1 or = < before the start of study treatment, with the exception for alopecia (hair loss).
5. You have been treated with any hematopoietic colony-stimulating growth factors (e.g., Granulocyte colony stimulating factor [G-CSF), Granulocyte Macrophage Colony Stimulating Factor [GM-CSF]) = < 2 weeks prior to starting study drug. However, you may be enrolled if your erythropoietin or darbepoetin therapy initiated at least 2 weeks prior to enrollment.
6. You have symptomatic CNS (central nervous system) metastasis which is neurologically unstable or those who have CNS disease requiring increase in the dose of steroid. (Note: If you have controlled CNS metastasis, you can participate in the trial. Before entering the study, you should have finished radiotherapy, or have received operation for CNS tumor metastasis at least two weeks before. Neurological function must be in a stable state; no new neurological deficit is found during clinical examination and no new abnormality is found during CNS imaging examinations. If you need to use steroids to treat CNS metastasis, the therapeutic dose of steroid should be stable for = > 3 months at least two weeks prior to entering the study with treatment dose no more than dexamethasone 4 mg daily or an equivalent dose of steroids).
7. You have received major surgery or had significant traumatic injury within 28 days prior to the first dose of the investigational product or have not recovered from major side effects.
8. You have known human immunodeficiency virus (HIV) infection by development of acquired immunodeficiency syndrome (AIDS) within the past 12 months; or you have active hepatitis B or hepatitis C.
9. You have a history of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis.
10. You have clinically significant cardiovascular disease
11. You have symptomatic visceral disease or any disease burden that makes you ineligible for receiving study drug per your doctor's judgment.
12. Evidence of past or current primary malignancies other than OCCC (except for non-melanoma skin cancer, in situ breast cancer or in situ cervical carcinoma and superficial bladder cancer, or other cancer curatively treated and with no evidence of disease for at least 5 years).
13. You have an established diagnosis of diabetes mellitus including steroid-induced diabetes mellitus.
14. You have any other concurrent disease which had potential risk of insulin resistance (e.g., pancreatic disorders, acromegaly, Cushing's syndrome) or current use of medication with potential risk of insulin resistance.
15. You are currently receiving or has received systemic corticosteroids = < 2 weeks prior to starting study treatment, or have not fully recovered from side effects of such treatment. Note: The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular).
16. Gastrointestinal condition which could impair absorption of study medication (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
17. You have any other concurrent severe and/or uncontrolled medical condition that would, in your doctor's judgment, contraindicate patient participation in the clinical study.
18. You have currently documented pneumonitis. You have a history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment or any evidence of clinically active ILD. Yours with a history of lung interstitial lesion or immune-related pneumonitis indicated by imaging.
19. You are pregnant, possibly pregnant, or breast-feeding. Pregnancy refers to the state of a woman between fertilization and the end of pregnancy confirmed by positive laboratory hCG test (> 5 mIU/mL). Breast-feeding woman can become eligible for this study if she permanently stops breast-feeding, however, cannot restart the breast-feeding during and after the completion of the study treatment.
20. You are of childbearing potential and neither you nor your partner are using effective contraception (e.g. intrauterine device (IUD), diaphragm with spermicide*, cervical cap* with spermicide, male condoms, female condoms* with spermicide) during the trial and within 6 months after the end of treatment. *Note that diaphragm with spermicide, cervical cap with spermicide, female condoms with spermicide are not approved in Japan.

Related Information

• Primary Sponsor: Kitano Tina