Phase II study of pevonedistat plus niraparib in patient with recurrent ovarian cancer
- Conditions
- ovarian cancer
- Registration Number
- JPRN-jRCT2031210181
- Lead Sponsor
- Hasegawa Kosei
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Suspended
- Sex
- Female
- Target Recruitment
- 33
1. Female patients aged 20 years or older at the time of informed consent.
2. Patients who are free to give written consent before performing the study-related procedures (excluding standard medical practice) after understanding that consent can be withdrawn at any time without disadvantage for future treatment.
3. Patients with a histological diagnosis of epithelial ovarian cancer excluding mucinous carcinoma (excluding borderline ovarian malignancy).
4. Patients who have received two or more lines of prior chemotherapy (including platinum-containing chemotherapy). However, patients with platinum resistance (disease progression less than 6 months after completion of platinum-containing chemotherapy) can be enrolled on a single prior line.The last course of antineoplastic drug therapy must be completed by 4 weeks before the start of study treatment.
5. Patients with at least one measurable lesion based on RECIST 1.1
6. Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status of 1 or less
7. Patients with preserved adequate organ function and laboratory values within 14 days prior to enrollment meeting the following criteria:
a. Absolute neutrophil count: >=1500/microL
b. Platelet count :>=150,000/microL
c. Hb level: >=10 g/dL
d. Albumin: >=2.7 g/dL
e. Serum creatinine level: <=1.5 x upper limit of normal (ULN) or creatinine clearance level by Cockcroft-Gault equation: >=50 mL/min
f. Total bilirubin: <=ULN (patients with Gilbert's syndrome can be included if direct bilirubin is <=1.5 x ULN)
g. AST and ALT:<=2.5 x ULN (<=5.0 x ULN for liver metastases)
8. Patients in whom formalin-fixed paraffin-embedded tissue specimens of primary or recurrent tumors can be submitted for biomarker evaluation or who can undergo biopsy of tumor tissue prior to the start of the study.
9. Those who can be given niraparib orally
10. Women who meet the following criteria:
a. menopausal status for more than 1 year before enrollment,
b. undergoing contraceptive surgery,
c. Women of childbearing potential agree to take two contraceptive methods simultaneously, one very effective contraceptive method and one effective barrier method, from the time of informed consent to 180 days after the last dose of study drug, or
d. If lifestyle is met (no sexual intercourse in normal lifestyle), consent should be made to avoid sexual intercourse completely (e.g., cyclic abstinence [e.g., calendar, ovulation, basal temperature, postovulatory contraception, etc.]); condoms only, removal, spermicide only, and breastfeeding amenorrhea are not appropriate contraceptive methods; female and male condoms should not be used at the same time).
1. Patients who received palliative radiation therapy to more than 20% of the bone marrow within 1 week before the start of study treatment
2. Patients with at least Grade 3 haematological toxicities or fatigue equivalent to at least Grade 3 lasting more than 4 weeks during the previous chemotherapy.
3. In patients treated with PARP inhibitors, patients with disease progression occurred in the first 6 months of treatment with PARP inhibitors or treated with niraparib at the previous treatment
4. Patients who received pelvic radiotherapy for treatment of primary or recurrent disease within 1 year before the start of study treatment
5. Patients diagnosed, detected, or treated for invasive malignancies other than ovarian cancer within 2 years before enrollment (excluding basal cell carcinoma or squamous cell carcinoma of the skin for which radical treatment was performed). However, patients with a history or current history of MDS or AML will be excluded regardless of the time of disease.
6. Patients with symptomatic, uncontrolled brain metastases or leptomeningeal metastases. Radiotherapy and surgical treatment of CNS lesions must be performed at least 1 month before enrollment in order to be considered well controlled. There are no new or progressive clinical signs related to CNS involvement, and steroids have been administered at a fixed dosage and administration or not at all for at least 4 weeks before enrollment. Imaging is not required to confirm the absence of brain metastases at baseline. Patients with spinal cord compression lesions may be enrolled if they receive definitive treatment for the lesion and evidence suggests clinical stability for 28 days.
7. Patients with unstable angina pectoris, clinically significant arrhythmias, congestive heart failure (grade III or IV according to NYHA severity grading), symptomatic cardiomyopathy either occurring within 6 months prior to the first dose of study drug, or a recent myocardial infarction (within 6 months prior to the first dose) or known cardiopulmonary disease defined as severe pulmonary hypertension.
8. Patients with corrected QT-interval (QTcF) >= 500 msec according to Fridericia method.
9. Patients with left ventricular ejection fraction (LVEF) <50%.
10. Patients with known interstitial lung disease, pulmonary fibrosis, or moderate to severe chronic obstructive pulmonary disease
11. Patients considered to be at high medical risk due to uncontrolled serious diseases (hypertension, cirrhosis or severe liver dysfunction, coagulopathy or hemorrhagic disease, major epileptic disorder, unstable spinal cord compression lesion, superior vena cava syndrome, intestinal obstruction or other serious gastrointestinal disease, etc.)
12. Patients with active infections or severe infectious diseases such as severe pneumonia, meningitis or sepsis.
13. Patients who underwent major surgery (at the discretion of the investigator, etc.) within 2 weeks before the start of study treatment. Or patients scheduled for surgery during the study period. The patient must be recovering from all the effects of major surgery.
14. Immunosuppressed patients (patients who have undergone splenectomy are acceptable) .
15. Patients who are hypersensitive to the ingredients of the investigational product or related compounds.
16. Patients who received any other investigational product, blood transfusion (platelets or red blood cells), or live virus and bacterial vaccine within 4 weeks before the start of study tre
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall Response Rate
- Secondary Outcome Measures
Name Time Method