NCT03263650已完成2 期
Randomized Phase II Study of Olaparib Maintenance Following Cabazitaxel-Carboplatin Induction Chemotherapy in Men With Aggressive Variant Prostate Cancer (AVPC)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS) of men with AVPC treated with 6 cycles of cabazitaxel + carboplatin followed by olaparib maintenance versus observation
研究概览
简要总结
The goal of this clinical research study is to learn if olaparib, when given after treatment with cabazitaxel, carboplatin, and prednisone, can help to control aggressive variant prostate cancer (AVPC). The safety of these drugs will also be studied.
This is an investigational study. Cabazitaxel and carboplatin are FDA approved and commercially available for the treatment of certain types of prostate cancer. Prednisone is FDA-approved and commercially available as a corticosteroid. Olaparib is FDA approved and commercially available for the treatment of certain types of ovarian cancer. The combination of cabazitaxel and carboplatin followed by olaparib in this study is investigational.
The study doctor can describe how the study drugs are designed to work.
Up to 96 participants will be enrolled on this study. All will take part at MD Anderson.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in a roll of dice) to 1 of 2 study groups. This is done because no one knows if one study group is better, the same, or worse than the other group. You will have a 2 in 3 chance of being assigned to Group 1 and a 1 in 3 chance of being assigned to Group 2:
- If you are in Group 1, you will receive olaparib.
- If you are in Group 2, you will not receive olaparib.
All participants will receive cabazitaxel and carboplatin.
You and the study staff will know to which group you have been assigned.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •1. Provision of informed consent prior to any study specific procedures.
- •2. Provision of informed consent for genetic research. If a patient declines to participate in the genetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent to that part.
- •3. Patients must agree to tissue collection for correlative studies at the specified timepoints. If patient has undergone a recent tissue collection without intervening treatment since, that can be retrieved and is deemed of sufficient quantity by the PI to undertake the proposed correlative studies, it may be used as the baseline.
- •4. Male aged 18 years and above.
- •5. Histologically or cytologically confirmed prostate carcinoma.
- •6. Presence of metastatic disease documented on imaging studies (bone scan, computed tomography (CT) and/or magnetic resonance imaging (MRI) scans).
- •7. Patients must meet at least one of the following AVPC criteria: i. Histologically proven small cell (neuroendocrine) prostate carcinoma ii. Exclusive visceral metastases. iii. Predominantly lytic bone metastases identified by plain x-ray or CT scan. iv. Bulky (\>/= 5cm in longest dimension) lymphadenopathy or high-grade tumor mass in prostate/pelvis. v. Low PSA (\/= 20) bone metastases. vi. Elevated serum lactate dehydrogenase (\>/=2 x upper limit of normal) or elevated serumcarcinoembryonic antigen (\>/= 2 x upper limit of normal ) in the absence of other etiologies. vii. Short interval (\/= 1.0 ng/mL; b) New or increasing non-bone disease (RECIST); c) Positive bone scan with 2 or more new lesions (PCWG3). d) Increasing symptoms unequivocally attributed to disease progression as judged by the treating physician and the PI.
- •10. Surgically or ongoing medically castrated, with baseline testosterone levels of \/= 10.0 g/dL dL (unless due to bone marrow infiltration by tumor, in which case hemoglobin \>/=8gdL is allowed). Patient may have blood transfusions prior to study enrollment. ii. Absolute neutrophil count (ANC) \>/= 1.5 x 10\^9/L (unless due to bone marrow infiltration by tumor, in which case ANC \>1,000/mm3 is allowed) iii. White blood cells (WBC) \>3x10\^9/L (unless due to bone marrow infiltration by tumor, in which case WBC \>2x109/L is allowed) iv. No features suggestive of myelodysplastic syndrome/acute myeloid leukemia on peripheral blood smear v. Platelet count \>/= 100 x 10\^9/L (unless due to bone marrow infiltration by tumor, in which case platelet \>/=50,000/ mm3 is allowed) vi. Total bilirubin \/= 40 mL/min.
- •14. Able to swallow study drugs whole as a tablet/capsule.
- •15. Patients who have partners of childbearing potential (e.g. female that has not been surgically sterilized or who are not amenorrheic for \>/= 12 months) must be willing to use a method of birth control in addition to adequate barrier protection as determined to be acceptable by the investigator during the study and for 13 weeks after last study drug administration. Please note that the efficacy of hormonal contraception may be decreased if administered with olaparib.
- •16. 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.
排除标准
- •1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at MD Anderson)
- •2. Previous enrolment or randomization in the present study
- •3. Any prior treatment for castration-resistant prostate cancer (CRPC) with carboplatin, cisplatin, cabazitaxel or olaparib.
- •4. Patients whose disease is refractory (defined as evidence of disease progression while on drug or within 3 months of its discontinuation) to more than 2 lines of chemotherapy given for CRPC. Any number of chemotherapies to which the patient's disease is not refractory are allowed, as long as time on treatment did not exceed 6 months (counted from day 1 of cycle 1 to day 1 of the last cycle of treatment).
- •5. Patients who have not recovered from adverse events secondary to systemic therapy (except for luteinizing hormone-releasing (LHRH) hormone agonist or antagonist treatment for prostate cancer, and bisphosphonates or receptor activator of Nf kappa (RANK) ligand inhibitors for bone strengthening), major surgery or radiotherapy for the treatment of prostate cancer to a grade \/= common terminology criteria for adverse events grade 2) with the exception of alopecia, caused by previous cancer therapy.
- •7. Chronic use of known strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin, voriconazole, nefazodone, posaconazole, ritonavir, lopinavir/ritonavir, indinavir, saquinavir, boceprevir, telaprevir and nelfinavir), moderate CYP3A4 inhibitors (e.g. amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil), strong CYP3A4 inducers (e.g. phenytoin, rifampicin, carbamazepine, St.John's Wort, phenobarbital) and moderate CYP3A4 inducers (e.g. bosentan, efavirenz, etravirine, modafinil and nafcillin). Concomitant use of these drugs with olaparib is not allowed. Patients may undergo limited courses of them prior to starting olaparib but will be required to have \>/= 5 week washout period from phenobarbital, and \>/=3 week washout period from the rest, before randomization.
- •8. Active uncontrolled infection ( patients completing a course of antibiotic or antiviral therapy whose infection is deemed to be controlled may be allowed on study after discussion with the PI; the PI will serve as the final arbiter regarding eligibility).
- •9. Active or symptomatic viral hepatitis or chronic liver disease.
- •10. A diagnosis or suspicion of myelodysplastic syndrome/acute myeloid leukemia.
- •11. A history of pneumonitis or extensive bilateral lung disease of non-malignant etiology.
- •12. A malignancy \[other than the one treated in this study\] which required radiotherapy or systemic treatment within the past 5 years, or has a \>/= 30% probability of recurrence within 24 months (except for adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the Ta urothelial carcinomas).
- •13. Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, superior vena cava syndrome, extensive bilateral lung disease on high-resolution computed tomography scan, uncontrolled seizures or any psychiatric disorder that prohibits obtaining informed consent.
- •14. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
- •15. Patients with symptomatic uncontrolled brain metastases or spinal cord compressions. A scan to confirm the absence of brain metastases is not required. 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.
- •16. Patients with a known hypersensitivity to the olaparib, carboplatin or cabazitaxel.
- •17. Prisoners or subjects who are involuntarily incarcerated.
- •18. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.
研究组 & 干预措施
Cabazitaxel + Carboplatin
Experimental
Cabazitaxel, Cabazitaxel and Carboplatin intravenously on day 1 of cycles 1-6. Prednisone by mouth twice daily on days 1-21 of cycles 1-6.
干预措施: Cabazitaxel (Drug)
Observation Only
No Intervention
Participants randomized to observation only beginning cycle 7.
Cabazitaxel + Carboplatin
Experimental
Cabazitaxel, Cabazitaxel and Carboplatin intravenously on day 1 of cycles 1-6. Prednisone by mouth twice daily on days 1-21 of cycles 1-6.
干预措施: Prednisone 5Mg (Drug)
Cabazitaxel + Carboplatin
Experimental
Cabazitaxel, Cabazitaxel and Carboplatin intravenously on day 1 of cycles 1-6. Prednisone by mouth twice daily on days 1-21 of cycles 1-6.
干预措施: Carboplatin (Drug)
Olaparib Maintenance
Experimental
Participants randomized to receive Olaparib by mouth twice daily on Day 1 of cycle 7.
干预措施: Olaparib (Drug)
结局指标
主要结局
Progression-free survival (PFS) of men with AVPC treated with 6 cycles of cabazitaxel + carboplatin followed by olaparib maintenance versus observation
时间窗: Up to one year from time of randomization
Progression Free Survival (PFS) calculated as the time from randomization until any one of the following events occurs, whichever comes first: * Documented disease progression * Start of a new therapy in the absence of progression * Death in the absence of progression
次要结局
- Genomic alterations in DNA damage repair (DDR) pathway genes induced and/or selected by carboplatin and cabazitaxel chemotherapy [biopsy #2 vs biopsy #1]: Association with clinical outcome (PFS>6 months)(Up to one year)
- Rate of adverse events possibly, probably or definitely attributable to olaparib following cabazitaxel plus carboplatin in men with AVPC(Up to one year)
- Overall survival (OS) of men with AVPC treated with 6 cycles of cabazitaxel + carboplatin followed by olaparib maintenance vs observation(Up to one year)
- Response evaluation criteria in solid tumors (RECIST) and prostate specific antigen (PSA) response rate (RR) to cabazitaxel + carboplatin induction, and to olaparib maintenance in men with AVPC(Up to one year)
- Association between DDR pathway gene expression changes following carboplatin + cabazitaxel chemotherapy and clinical outcome (PFS>6 months)(Up to one year)
- Collection and archiving of serum, plasma, and urine samples in study patients for later hypothesis generating associations(Up to one year)
研究者
研究点 (1)
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