Magnetic Resonance (MR) Imaging With Hyperpolarized Pyruvate (13C) as a Predictive Biomarker of Response to Androgen Signaling Inhibitors in Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Mean difference in baseline intra-tumoral peak lac/pyr ratio on HP C-13 MRI in ASI-refractory versus ASI-responsive CRPC tumors
研究概览
简要总结
This is a prospective imaging study evaluating the utility of baseline metabolic MR imaging with Hyperpolarized Pyruvate (HP) (13C) as a predictive response biomarker to androgen signaling inhibition in patients with castration-resistant prostate cancer.
详细描述
This is a prospective imaging study evaluating the utility of baseline metabolic MR imaging as a predictive response biomarker to androgen signaling inhibition in patients with castration-resistant prostate cancer. Patients with a target lesion that is amenable for metabolic MR imaging will be eligible for study participation. Patients will undergo baseline metabolic MR imaging with Hyperpolarized Pyruvate C-13 pyruvate followed by initiation of androgen signaling inhibition (either as standard of care or as part of clinical trial; including abiraterone and/or enzalutamide treatment). Patient will subsequently undergo repeat metabolic MR scan after 28 days (+/- 7 days) of therapy. For those without primarily refractory disease, a third metabolic MR scan will be completed at the time of radiographic disease progression by The Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria. MR- or CT-guided tumor biopsies are optional at baseline and at the time of disease progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Biopsy-proven prostate cancer.
- •Progressive, castration-resistant disease according to PCWG2 criteria.
- •Planned treatment with an androgen signaling inhibitor (e.g., abiraterone, enzalutamide, apalutamide (ARN-509)). Patients must not be receiving androgen signaling inhibitor at the time of the baseline MR scan. Combination treatment (e.g., androgen signaling inhibitor in conjunction with another systemic treatment) is allowed.
- •Presence of at least one target lesion detected by standard staging scans that, in the judgment of Study Investigators, would be amenable to hyperpolarized C-13 pyruvate/metabolic MR imaging:
- •Soft tissue/visceral organ target lesions must measure at 1.5 cm in long axis diameter on CT or MRI.
- •Target lesions in the bone must be visualized by CT or MRI (lesions present only on bone scan do not qualify).
- •For patients with target lesion in prostate/prostatic bed:
- •i. No contra-indications to endorectal coil insertion (e.g., patients with a prior abdominoperineal resection of the rectum or latex allergy).
- •ii. No prior local treatment to the selected lesion. Patients who have received prior radiation or ablative therapy to the prostate will be required to have biopsy-proven evidence of disease recurrence following completion of local therapy.
- •The subject is able and willing to comply with study procedures and provide signed and dated informed consent.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Adequate organ function, including absolute neutrophil count (ANC) ≥ 1500 cells/µL, hemoglobin ≥ 9.0 gm/dL, platelets ≥ 75,000 cells/µL, creatinine < 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min (by the Cockcroft Gault equation), bilirubin <1.5x ULN (unless Gilbert's is suspected in which case total bilirubin < 3 x ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.5x ULN.
- •For patients undergoing optional tumor biopsy:
- •No history of bleeding diathesis.
- •Patients on anti-coagulation they must be able to safely stop treatment for purposes of tumor biopsy.
- •For patients with partners of childbearing potential, willing to use adequate contraception for one month after undergoing HP pyruvate infusion.
- •Patients must have prior bilateral orchiectomy or be on continuous luteinizing-hormone releasing hormone (LHRH) analogue therapy for the duration of study.
- •Castrate level of serum testosterone (< 50 ng/dL) at study entry.
排除标准
- •Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
- •Patients unwilling or unable to undergo MR imaging, including patients with contra-indications to MRI, such as cardiac pacemakers or non-compatible intracranial vascular clips.
- •Metallic hip implant or any other metallic implant or device that distorts local magnetic field and compromises the quality of MR imaging.
- •Poorly controlled hypertension, defined as systolic blood pressure at study entry greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg. The addition of anti-hypertensives to control blood pressure is allowed.
- •Congestive heart failure or New York Heart Association (NYHA) status ≥
- •A history of clinically significant EKG abnormalities, including QT prolongation (QTcF > 500 ms), a family history of prolonged QT interval syndrome, or myocardial infarction (MI) within 6 months of study entry. Patients with rate-controlled atrial fibrillation/flutter will be allowed on study.
- •Any condition that, in the opinion of the Principal Investigator, would impair the patient's ability to comply with study procedures.
研究组 & 干预措施
MR imaging with hyperpolarized 13C pyruvate of men with CRPC
75 men with castration-resistant prostate cancer (CRPC) will undergo MR imaging with hyperpolarized 13C pyruvate of a pre-selected target lesion at baseline and after 1 month of treatment with an androgen signaling inhibitor. Patients with CRPC that is not primarily refractory (defined as disease progression by PCWG2 criteria within 6 months of treatment initiation) to Androgen Signaling Inhibitors (ASI) treatment will undergo a third metabolic MR scan at the time of disease progression. Patients may undergo optional MR- or CT-guided tumor biopsies at baseline and at the time of disease progression.
干预措施: Pyruvate (13C) (Drug)
MR imaging with hyperpolarized 13C pyruvate of men with CRPC
75 men with castration-resistant prostate cancer (CRPC) will undergo MR imaging with hyperpolarized 13C pyruvate of a pre-selected target lesion at baseline and after 1 month of treatment with an androgen signaling inhibitor. Patients with CRPC that is not primarily refractory (defined as disease progression by PCWG2 criteria within 6 months of treatment initiation) to Androgen Signaling Inhibitors (ASI) treatment will undergo a third metabolic MR scan at the time of disease progression. Patients may undergo optional MR- or CT-guided tumor biopsies at baseline and at the time of disease progression.
干预措施: MRI (Device)
结局指标
主要结局
Mean difference in baseline intra-tumoral peak lac/pyr ratio on HP C-13 MRI in ASI-refractory versus ASI-responsive CRPC tumors
时间窗: Up to 6 months
ASI-refractory disease is defined as progression by PCWG2 criteria within 6 months of treatment initiation. ASI-responsive disease includes all other tumors not meeting this criterion. A two sample t-test will be used to compare the mean intra-tumoral HP lac/pyr ratio between treatment-refractory versus treatment-responsive tumors. If a non-parametric distribution is observed, a Mann-Whitney test may also be used to compare the two groups.
次要结局
- Mean percent change from baseline in peak intra-tumoral HP lac/pyr ratio on repeat metabolic MRI(Up to 6 months)
- Baseline peak intra-tumoral HP lac/pyr ratio cut-point that most accurately predicts for response versus refractoriness to subsequent ASI treatment(Baseline)
- Mean Intra-patient reproducibility of HP lac/pyr ratio(Up to 6 months)
- Association between change from baseline in peak intra-tumoral HP lac/pyr ratio after 28 days of ASI treatment with subsequent clinical outcomes on ASI treatment(Up to 28 days)
- Frequency of clinically significant changes in safety variables over time(Up to 6 months)
研究者
Rahul Aggarwal
Rahul Aggarwal, MD
University of California, San Francisco