A Randomized Trial of High-risK metachroNous oligometastatIc Prostate Cancer With hiGh-risk Mutations Treated witH meTastasiS Directed Therapy and Niraparib/Abiraterone Acetate and Prednisone (KNIGHTS)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 88
- 试验地点
- 2
- 主要终点
- PSA (Prostate Specific Antigen) evaluation at the 18-month progression of both treatment arms
研究概览
简要总结
The purpose of this research study is to compare the effects, good and/or bad, of using the standard of care treatment, hormonal therapy + Stereotactic Ablative Radiation (SABR) to the metastatic lesions, compared to standard of care and addition of 6-months of niraparib/abiraterone acetate combination pills and prednisone for participants with recurrent metastatic prostate cancer.
详细描述
In this trial all participants will be randomized to one of the two groups. You will be randomly assigned (by chance, like the flip of a coin) to one of the two groups: 1: Standard of care treatment (hormonal therapy + SABR to the metastatic lesions) or 2: Standard of care treatment + 6-months of niraparib/abiraterone acetate combination pills and prednisone. Participants in both groups will receive rectal swabs and various blood tests to assess circulating tumor cells, genomic sequencing, and tumor markers. Both groups will also participate in quality-of-life surveys
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •≥18 years of age (or the local legal age of consent).
- •Patient must have at least one and up to three asymptomatic metastatic tumor(s) of the bone, soft tissue, or extra-pelvic nodal region each < 5 cm or < 250 cm3 that develop within the past 6-months that are seen on imaging. A nodal lesion is defined to include nodal conglomerates located in the same nodal chain such that they can be treated in one SABR field. Up to five lesions are allowed on advanced functional imaging such as fluciclovine (Axumin), choline or Prostate Specific Membrane Antigen (PSMA) PET-CT scan.
- •CT or MRI scan within 6 months of enrollment
- •Bone scan within 6 months of enrollment
- •Fluciclovine (Axumin), choline, or PSMA PET-CT scan within 6 months of enrollment (PET-CT scan is reasonable for study entry imaging as an alternative to CT/MRI scan and bone scan)
- •Must have a high-risk pathogenic mutation (TP53, BRCA1/2, PALB2, ATM, BRIP1, CHEK2, FANCA, RAD51B, RAD54L, MUTYH) by next generation sequencing. ATM mutation enrollment will be capped at 5% of the overall population.
- •Histologic confirmation of prostate adenocarcinoma (primary or metastatic tumor).
- •Patient may have had prior systemic therapy and/or ADT so long as testosterone is > 100 ng/dl prior to enrollment
- •PSA > 0.5 but <50 at enrollment.
- •Prostate Specific Antigen Doubling Time (PSADT) < 15 months
- •Baseline testosterone > 100 ng/dl
- •Patient must have a life expectancy ≥ 12 months.
- •Patient must have an ECOG performance status ≤
- •Adequate hematologic, renal, and hepatic function at screening defined as follows:
- •Absolute neutrophil count ≥1.5 x 109/L
- •Hemoglobin ≥9.0 g/dL, independent of transfusions for at least 28 days
- •Platelet count ≥100 x 109/L
- •Creatinine <2 x upper limit of normal (ULN)
- •Serum potassium ≥3.5 mmol/L
- •Serum total bilirubin ≤1.5× ULN or direct bilirubin ≤1 x ULN (Note: In participants with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin, and if direct bilirubin is ≤1.5 × ULN, participant may be eligible)
- •AST or ALT ≤3 × ULN
- •Patient must have the ability to understand and the willingness to sign a written informed consent document
- •Able to swallow the study medication tablets whole.
- •While on study medication and for 4 months following the last dose of study medication, a male participant must agree to use condom and an adequate contraception method for female partner (WOCBP) A male participant must agree not to donate sperm while on study treatment and for a minimum of 4 months following the last dose of study medication.
- •Castration-resistant prostate cancer (CRPC).
- •Prior radiation therapy to an overlapping site of a target lesion that would preclude further radiation therapy
- •Spinal cord compression or impending spinal cord compression.
- •Suspected intracranial and/or liver metastases (>10 mm in largest axis).
- •Patient receiving any other investigational agents.
- •Inability to receive any form of systemic therapy in the opinion of a treating medical oncologist.
- •Unable to lie flat during or tolerate PET/MRI, PET/CT or SABR.
- •Radiographical evidence of cranial parenchymal metastasis.
- •Active second primary malignancy; AML/MDS in medical history.
- •Uncontrolled hypertension and myocardial infarction/PE/cardiac failure in last 6 months.
- •Prior treatment with PARP inhibitor
- •Refusal to sign informed consent.
- •Pathological finding consistent with small cell or neuroendocrine carcinoma of the prostate.
- •History of adrenal dysfunction
- •Long-term use of systemically administered corticosteroids (>5mg of prednisone or the equivalent) during the study is not allowed. Short-term use (≤4 weeks, including taper) and locally administered steroids (eg, inhaled, topical, ophthalmic, and intra-articular) are allowed, if clinically indicated.
- •Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are:
- •non-muscle invasive bladder cancer.
- •skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured.
- •malignancy that is considered cured with minimal risk of recurrence.
- •History or current diagnosis of MDS/AML.
- •Current evidence within 6 months prior to randomization of any of the following:
- •severe/unstable angina, myocardial infarction, symptomatic congestive heart failure,
- •clinically significant arterial or venous thromboembolic events (ie. Pulmonary embolism), or clinically significant ventricular arrhythmias.
- •Presence of sustained uncontrolled hypertension (systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg). Participants with a history of hypertension are allowed, provided that blood pressure is controlled to within these limits by an antihypertensive treatment.
- •Known allergies, hypersensitivity, or intolerance to the excipients of niraparib/abiraterone acetate tablets
- •Current evidence of any medical condition that would make prednisone use contraindicated.
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排除标准
- 未提供
研究组 & 干预措施
Androgen deprivation therapy + Stereotactic ablative radiation + niraparib/abiraterone acetate
干预措施: Stereotactic ablative radiation therapy (SABR) (Radiation)
Androgen deprivation therapy + Stereotactic ablative radiation
干预措施: Stereotactic ablative radiation therapy (SABR) (Radiation)
Androgen deprivation therapy + Stereotactic ablative radiation
干预措施: Androgen deprivation therapy (ADT) (Drug)
Androgen deprivation therapy + Stereotactic ablative radiation + niraparib/abiraterone acetate
干预措施: niraparib/abiraterone acetate (Drug)
Androgen deprivation therapy + Stereotactic ablative radiation + niraparib/abiraterone acetate
干预措施: Androgen deprivation therapy (ADT) (Drug)
结局指标
主要结局
PSA (Prostate Specific Antigen) evaluation at the 18-month progression of both treatment arms
时间窗: 18 months
PSA evaluation of progression at 18-month PSA , defined as PSA \> 0.2 ng/mL in patients initially treated with radical prostatectomy and greater than nadir + 2 ng/mL for patients initially treated with definitive radiation, with testosterone \>100 ng/dl of men who have oligometastatic castration-sensitive prostate cancer with high-risk mutations (TP53, BRCA1/2, PALB2, ATM, BRIP1, CHEK2, FANCA, RAD51B, RAD54L, MUTYH) treated with ADT + SABR MDT (6-mos) versus ADT + SABR MDT + niraparib/abiraterone acetate and prednisone (6-mos).
次要结局
- Local control at 18 months after ADT+ SABR MDT (6-mos) vs ADT + SABR MDT + niraparib/abiraterone acetate and prednisone (6-mos) in patients with metachronous oligometastatic Castrate Specific Prostate Cancer (CSPC) disease.(18 months)
- Time to locoregional progression, time to distant progression, time to new metastasis, radiographic progression-free survival and duration of response after randomization(4 years)
- Quality-of-life measured through EPIC tool following completion of ADT+ SABR MDT (6-mos) vs ADT + SABR MDT + niraparib/abiraterone acetate and prednisone (6-mos).(4 years)
- Treatment-related adverse events of both treatment arms(4 years)
研究者
Jason Molitoris, MD PhD
Principal Investigator
University of Maryland, Baltimore