PEACE V: a Randomized Phase II Trial for the Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases (STORM)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 196
- 试验地点
- 29
- 主要终点
- Metastases-free survival
研究概览
简要总结
A proportion of prostate cancer (PCa) patients develop relapse following curative local treatment. Regional nodal recurrence is an emerging clinical situation since the introduction of new molecular imaging methods in the restaging of recurrent prostate cancer. More specifically, a subgroup of these patients is being diagnosed with a recurrence confined to the regional lymph nodes and limited in number (oligorecurrence) using choline or PSMA PET-CT. As there are no specific treatment recommendations for these type of patients, different treatment approaches are currently used, mostly focusing on local ablative treatments using radiotherapy or surgery. These treatments are coined metastasisdirected therapy (MDT). MDT in combination with or without temporary ADT could delay the subsequent risk of progression, and even cure limited regional nodal recurrences. Consequently, lifelong palliative ADT, with its toxicity and excess in non-cancer mortality might be postponed.
The proposed trial randomizes patients with oligorecurrent nodal prostate cancer following primary PCa treatment to either metastasis-directed therapy (MDT) (salvage lymph node dissection, sLND or stereotactic body radiotherapy, SBRT) or MDT plus whole pelvis radiotherapy (WPRT: 45 Gy in 25 fractions).
详细描述
A proportion of prostate cancer (PCa) patients develop a local, regional (N1) or distant (M1) relapse following curative local treatment. For both local and distant relapses, different treatment recommendations are made in the guidelines (EAU guidelines 2016). However, the entity regional nodal recurrence is not mentioned in the guidelines but is an emerging clinical situation since the introduction of choline and more recently PSMA PET-CT in the restaging of recurrent prostate cancer. More specifically, a subgroup of these patients is being diagnosed with a recurrence confined to the regional lymph nodes and limited in number (oligorecurrence) using choline or PSMA PET-CT. As there are no specific treatment recommendations for these type of patients, different treatment approaches are currently used, mostly focusing on local ablative treatments using radiotherapy or surgery. These treatments are coined metastasisdirected therapy (MDT). MDT in combination with or without temporary ADT could delay the subsequent risk of metastases, and even cure limited regional nodal recurrences. Consequently, lifelong palliative ADT, with its toxicity and excess in non-cancer mortality might be postponed.
The proposed trial randomizes patients with oligorecurrent nodal prostate cancer following primary PCa treatment to either metastasis-directed therapy (MDT) (sLND or SBRT) or MDT plus WPRT. In the recurrent PCa setting, 2 recent trials have suggested a progression-free and even survival benefit of adding temporary ADT to local salvage prostate bed radiotherapy. Consequently, this positive effect might also be applicable for regional recurrences. Although the optimal duration of ADT is unknown, a minimal duration of 6 months of ADT seems advisable in this setting and will be mandatory for both arms.
This trial will improve our insights in the pattern of recurrence following these treatment modalities with the expectation that WPRT will reduce the number of nodal relapses, improving metastasis-free survival and postponing the need for palliative systemic treatments while maintaining quality-of-life. The current phase II trial will try to establish a golden standard in the treatment of oligorecurrent nodal PCa.
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
- •Histologically proven initial diagnosis of adenocarcinoma of the prostate
- •Biochemical relapse of prostate cancer following radical local prostate treatment (radical prostatectomy, primary radiotherapy or radical prostatectomy +/- prostate bed adjuvant/ salvage radiotherapy) according to the EAU guidelines
- •Following radical prostatectomy, patients with a biochemical relapse are eligible in case a nodal relapse is detected in the pelvis even in the absence of prior postoperative prostate bed radiotherapy (adjuvant or salvage).
- •In case of a suspected local recurrence following primary radiotherapy, a biopsy should confirm local recurrence and patients with a confirmed local recurrence are eligible in case they also undergo a local salvage therapy. If imaging rules out local relapse, patients are eligible.
- •Nodal relapse in the pelvis on choline, PSMA or FACBC PET-CT with a maximum of 3 positive nodal lymph nodes. The upper limit of the pelvis is defined as the aortic bifurcation.
- •WHO performance state 0-1
- •Age >18 years
- •Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
- •Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
排除标准
- •Bone or visceral metastases
- •Para-aortic lymph node metastases (above the aortic bifurcation)
- •Local relapse in the prostate gland or prostate bed not suitable for a curative treatment
- •Previous irradiation of the pelvic and or para-aortic nodes
- •Serum testosterone level <50ng/dl or 1.7 nmol/L at time of randomization
- •Symptomatic metastases
- •Lymph node metastases in previously irradiated areas resulting in dose constraint violation
- •Contraindications to pelvic radiotherapy (chronic pelvic inflammatory bowel disease)
- •Contraindications to androgen deprivation therapy
- •PSA rise while on active treatment with (LHRH-agonist, LHRH-antagonist, anti-androgen, estrogen
- •Previous treatment with cytotoxic agent for PCa
- •Treatment during the past month with products known to influence PSA levels (e.g. fluconazole, finasteride, corticosteroids,...)
- •Other active malignancy, except non-melanoma skin cancer or other malignancies with a documented disease-free survival for a minimum of 3 years before randomization.
研究组 & 干预措施
MDT + ADT
Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + 6 months androgen deprivation therapy
干预措施: metastasis-directed treatment (Radiation)
MDT + ADT
Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + 6 months androgen deprivation therapy
干预措施: salvage Lymph Node Dissection (Procedure)
MDT + ADT
Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + 6 months androgen deprivation therapy
干预措施: androgen deprivation therapy (Drug)
MDT + WPRT + ADT
Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + whole pelvic radiotherapy + 6 months androgen deprivation therapy
干预措施: whole pelvic radiotherapy (Radiation)
MDT + WPRT + ADT
Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + whole pelvic radiotherapy + 6 months androgen deprivation therapy
干预措施: metastasis-directed treatment (Radiation)
MDT + WPRT + ADT
Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + whole pelvic radiotherapy + 6 months androgen deprivation therapy
干预措施: salvage Lymph Node Dissection (Procedure)
MDT + WPRT + ADT
Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + whole pelvic radiotherapy + 6 months androgen deprivation therapy
干预措施: androgen deprivation therapy (Drug)
结局指标
主要结局
Metastases-free survival
时间窗: 2 year
Metastasis-free survival will be defined as the time between randomization and the appearance of a metastatic recurrence (any M1) as suggested by choline, FACBC or PSMA PET-CT or death due to any cause
次要结局
- Clinical Progression free survival(2 year)
- Toxicity: acute toxicity(3 months)
- Patient reported QOL as per EORTC-QLQ C30(2 year)
- Time to start of hormonal treatment(2 year)
- Toxicity: late toxicity(2 year)
- Overall survival(5 year)
- Time to castration-resistant disease(5 year)
- Biochemical progression-free survival(2 year)
- Patient reported QOL as per EORTC-QLQ PR25(2 year)
- Prostate cancer-specific survival(5 year)
- economical evaluation(2 year)
- Sensitivity/specificity of PET-CT for the detection of nodal recurrences: limited to patients undergoing surgery(3 months)