ISRCTN14784018已完成2 期
Randomised phase II Trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 139
研究概览
简要总结
2021 Protocol article in https://pubmed.ncbi.nlm.nih.gov/33452192/ protocol (added 18/01/2021) 2024 Results article in https://doi.org/10.1038/s41416-023-02567-6 (added 22/01/2024)
研究设计
- 研究类型
- Interventional
入排标准
- 性别
- Female
入选标准
- •Current inclusion criteria as of 21/11/2019:
- •1. Female patients, age 16 years and older with epithelial ovarian, primary peritoneal or fallopian tube cancer who have relapsed within 12 months of previous platinum-based therapy. Their most recent chemotherapy does not have to have been platinum-based.
- •2. Patients can have received prior PARP inhibitor but there must be a > 6 month interval since treatment
- •3. Patients can have received prior anti-angiogenic therapy, but there must be a > 6 month interval since treatment; except for bevacizumab where a 6 week interval is required
- •4. Measurable disease by RECIST Version 1.1 performed in past 4 weeks. At least one lesion, not previously irradiated, that can be accurately measured at baseline as = 10 mm in the longest diameter (except lymph nodes which must have short axis = 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
- •5. Sufficient archival tissue confirming histological diagnosis available
- •6. ECOG PS 0-2
- •7. Able to swallow and retain oral medications
- •8. Life expectancy > 12 weeks in terms of disease related mortality
- •8. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
- •10. Written (signed and dated) informed consent prior to any study specific procedures and be capable of co-operating with protocol
- •11. Patients must have haemoglobin = 9.0 g/dL and no blood transfusions in the 28 days prior to randomisation
- •12. Patients must have normal organ and bone marrow function measured within 14 days prior to administration of study treatment as defined below:
- •12.1. Absolute neutrophil count (ANC) = 1.5 x 109/L
- •12.2. Platelet count > 100 x 109/L
- •12.3. Total bilirubin = 1.5 x institutional upper limit of normal (ULN)
- •12.4. AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be = 5x ULN
- •12.5. Serum creatinine = 1.5 x institutional upper limit of normal (ULN) or calculated creatinine clearance >50 ml/min calculated using Cockroft-Gault, Jelliffe or Wright (see Appendix 4)
- •12.6. Urine dipstick for proteinuria <2+. If urine dipstick is = 2+ on two occasions more than one week apart then a 24-hour urine must demonstrate = 1 g of protein in 24 hours or protein/creatinine ratio < 1.5
- •Previous inclusion criteria:
- •1. Female patients, age 16 years and older with relapsed BRCA (germline or somatic) mutated epithelial ovarian, primary peritoneal or fallopian tube cancer who have relapsed in a platinum resistant time frame, i.e. have progressed within 6 months of previous platinum-based therapy. Their most recent chemotherapy does not have to have been platinum-based.
- •2. Patients can have received prior PARP inhibitor and antiangiogenic therapy, but there must be a > 6 month interval since treatment
- •3. Measurable disease by RECIST Version 1.1 performed in past 4 weeks. At least one lesion, not previously irradiated, that can be accurately measured at baseline as = 10 mm in the longest diameter (except lymph nodes which must have short axis = 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
- •4. Sufficient archival tissue confirming histological diagnosis available
- •5. ECOG PS 0-2
- •6. Able to swallow and retain oral medications
- •7. Life expectancy > 12
排除标准
- •1. Received previous single agent weekly paclitaxel for relapsed disease
- •2. Pregnant or breast-feeding women or women of childbearing potential unless effective methods of contraception are used during the trial and for 6 months after stopping treatment. Negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1. Pregnancy test will be performed monthly in women of child bearing potential.
- •Postmenopausal is defined as: Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments, LH and FSH levels in the post-menopausal range for women under 50, radiation-induced oophorectomy with last menses >1 year ago, chemotherapy-induced menopause with >1 year interval since last menses, or surgical sterilisation (bilateral oophorectomy or hysterectomy).
- •3. Treatment with any other investigational agent, systemic chemotherapy, or participation in another interventional clinical trial within 28 days prior to enrolment
- •4. Radiotherapy within 2 weeks from the last dose prior to study treatment
- •5. Started a stable dose of bisphosphonates for bone metastases less than 4 weeks prior to treatment with study drug e.g. patient is eligible and can continue to take bisphosphonates if these were started at least 4 weeks prior to treatment with study drug
- •6. Concomitant use of known CYP3A4 inhibitors such as ketokonazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir
- •7. Concomitant use of potent inducers of CYP3A4 such as rifampicin, carbamazepine, phenobarbital, phenytoin and St. John Wort
- •8. Persistent toxicities (>=CTCAE grade 2), with the exception of alopecia, caused by previous cancer therapy
- •9. Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
- •10. Blood transfusions within 1 month prior to study start
- •11. Patients with myelodysplastic syndrome/acute myeloid leukaemia.
- •12. Patients with symptomatic, untreated, uncontrolled brain or meningeal metastases or tumour
- •12.1. A scan to confirm the absence of brain metastases is not require
- •12.2. Patients with radiological evidence of stable brain metastases are eligible, providing that they are asymptomatic and:
- •12.2.1. Do not require corticosteroids, or
- •12.2.2. Have previously been treated with corticosteroids, with clinical and radiological evidence of stabilisation at least 10 days after discontinuation of steroids
- •12.2.3. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment.
- •13. Major surgery within 14 days of starting study treatment
- •14. Patients who have not recovered from any effects of any major surgery.
- •15. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease on HRCT scan
- •16. Any psychiatric disorder that prohibits obtaining informed consent.
- •17. Left Ventricular Ejection Fraction (LVEF) < institutional lower limit of normal, when:
- •17.1. Prior treatment with anthracyclines
- •17.2. Prior treatment with trastuzumab
- •17.3. A NYHA cla
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