Early Rising PSA Endocrine Treatment Versus Chemo-endocrine Therapy- SPCG14
A Randomized, Open Label, Multicenter, Phase III, 2-Arm Study of Androgen Deprivation +/- Taxotere (Docetaxel) for Non-metastatic Prostate Cancer Patients With a Rising PSA
Summary
In patients with prostate cancer (PC) who have only biochemically relapsed disease after curative treatment (or some locally advanced PC patients), hormonal therapy remains a de facto standard of care treatment. Adding docetaxel-based chemotherapy to a standard-of-care hormonal therapy has an increased potential to treat prostate cancer cell clones resistant to androgen withdrawal and to possibly shorten the duration of therapy needed to control the disease.
This clinical trial is designed on the basis of an unmet clinical need, as well as other factors including: 1) a consensus among investigators on endpoints for studies of patients with a rising PSA, 2) the ability to identify subjects at high risk for developing radiographic metastases, 3) the fact that hormonal therapy has already been shown to improve survival when applied early in the natural history, and 4) the availability of chemotherapy such as docetaxel that can improve survival in subjects with advanced disease.
It is our hypothesis that a more appropriate group of patients who may benefit from the curative potential of systemic chemo-hormonal modality is that with minimal, but detectable disease who have a high probability of developing metastatic disease, clinical symptoms and eventually death from prostate cancer in a defined time frame. The investigators hypothesize further that the approach is likely to be more effective at a time of minimal tumour burden, resulting in minimization of the overall burden of therapy and better quality of life while on treatment.
This trial will determine whether any benefit is gained by adding chemotherapy to hormonal therapy alone in the population of subjects with a rising PSA. Two therapeutic approaches will be compared in this two-arm randomized clinical trial. The control Arm A provides antiandrogen (bicalutamide 150 mg x 1) alone. The experimental Arm B involves treatment with docetaxel for 8-10 cycles and antiandrogen (bicalutamide 150 mg x 1) treatment. For the schematic representation of study design please see Section 7.3.1.
Subjects with a rising PSA following definitive local curative therapy will be eligible, if their PSA doubling time is < 12 months. Also PC patients planned for anti-.androgen therapy are eligible, with the same criteria. Subjects with radiographic metastases will be excluded. The primary endpoint of the trial is progression-free survival of subjects that do not experience biochemical failure at 60 months from the start of therapy.
Based on the yearly number of prostate cancer patients who undergo definitive local therapies and the estimated probabilities of relapse, upwards of 400 men (if +15% improvement) in the Scandinavian countries are potential candidates for this approach.
研究概览
研究类型
注册 (实际的)
阶段
- 第三阶段
联系人和位置
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Men > 18 and ≤80 years of age.
- WHO/ECOG performance status 0 - 1 (WHO: World Health Organization; ECOG: Eastern Cooperative Oncology Group )
- Histological proven adenocarcinoma of the prostate.
- Patients who are planned to receive antiandrogen (bicalutamide 150 mg x 1) treatment,
After curative treatment
- Prostatectomy: PSA > 10 OR PSA DT < 12 months and PSA > 0.5 (PSA doubling time calculation must start at a minimum value of > 0.5)
- Radiation: PSA > +2.0 above nadir and PSA >10 OR PSA DT < 12 months and PSA > 0.5. (PSA bouncing after radiotherapy should be excluded according to the local traditions, and PSA doubling time calculation must start at a minimum value of > 0.5)
In locally advanced (or local not suitable for curative therapy) prostate cancer patients, PSA < 100 is required before inclusion AND one of the following
- PSA DT < 12 months or
- PSA >20 or
- Gleason score 8-10
- Previous hormonal therapy in conjunction with radiotherapy is allowed, provided that the total duration of therapy does not exceed 12 months and has to be stopped > 12 months ago.
- Testosterone value > 5 nmol/l
- Adequate haematological-, liver- and kidney function. WBC(white blood cell ) 3.5 x 109/L ANC(absolute neutrophil count ) 1.5 x 109/L Platelet Count 150 x 109/L Haemoglobin > 120 g/L Total bilirubin ≤ ULN (upper limit of normal) unless due to Gilbert's disease Creatinine ≤ 1.5 x ULN or creatinine clearance of 60 cc/min or corresponding Iohexol clearance value ASAT(aspartate aminotransferase )/ALAT(alanine aminotransferase) ≤ 1.5 x ULN ALP (Alkaline phosphatase) < 1.5 x ULN
- Negative bone scan performed no more than 3 months prior to randomisation.
- Additional CT or ultrasound of thorax, abdomen and/or pelvis is optional.
- Written informed consent.
Exclusion Criteria:
- Positive bone scan
- Any distant metastasis detected by CT or ultrasound
- Patients with a history of previous malignant disease. Exceptions should be made for basal cell carcinoma (BCC) and squamous cell carcinoma of the skin. Exceptions should also be made for curatively treated malignant disease, which has been disease free for the past 5 years.
- Previous chemotherapy or randomised in SPCG 12/AdPro or SPCG 13/AdRad (SPCG: Scandinavian Prostate Cancer Group).
- Systemic corticosteroids within 6 months prior to randomisation.
- Unstable cardiovascular disease, including myocardial infarction, within 6 months prior to randomisation.
- Active untreated infectious disease, including tuberculosis, MRSA (Methicillin-resistant Staphylococcus aureus.
- Active gastric ulcer.
- Known hypersensitivity to Polysorbate 80 (an excipient of docetaxel)
- Other serious illness or medical condition
- Symptomatic peripheral neuropathy ≥ CTCAE grade 2.
- Patients who by altered physical or psychological state not are able to co-operate or participate in the trial.
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
有源比较器：Antiandrogen
Antiandrogen (bicalutamide 150 mg x 1) p.o. alone,
|
|
|
实验性的：Antiandrogen + docetaxel
Antiandrogen (bicalutamide 150 mg x 1) p.o. + Docetaxel 75 mg/m2 (maximum 2.0 m2 ) i.v.
q 3 weeks x up to 8-10 cycles.
|
Antiandrogen (bicalutamide 150 mg x 1) + docetaxel (Taxotere®) 75mg/m2 (max 2.0m2) i.v. in 60 minutes on day 1. One cycle is 21 days. Docetaxel will be given for up to 8-10 cycles or until unacceptable toxicity or consent withdrawal whichever comes first. Antiemetic therapy may be used if necessary.
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Progression free survival
大体时间：From date of randomization until the date of first documented progression or date of death from any cause, which ever came first, assessed up to 60 months
|
Progression free survival defined as the time from randomization to the date of first documentation of:
These patients will be followed for evaluation of survival. - Death Death due to prostate cancer in the absence of previous documentation of disease progression, |
From date of randomization until the date of first documented progression or date of death from any cause, which ever came first, assessed up to 60 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Difference between groups in PSA doubling time (PSADT).
大体时间：From date of randomization until the date of first documented PSADT, assessed up to 60 months
|
The PSADT can be calculated by the natural log of 2 (0.693) divided by the slope of the relation between the log of PSA and the time of PSA measurement.
|
From date of randomization until the date of first documented PSADT, assessed up to 60 months
|
|
Difference between groups regarding QoL
大体时间：At date of randomization and yearly, assessed up to 60 months
|
The quality of life (QoL) will be assessed using the FACT-P-T disease-specific subscale.
The scoring will be in accordance with version 4 of the FACT manual.
|
At date of randomization and yearly, assessed up to 60 months
|
|
Difference between groups regarding metastasis free survival
大体时间：From date of randomization until the date of first documented date of metastases, assessed yearly by bone-scan after first PSA_progression until first sign of metastasis, whichever came first, assessed up to 100 months
|
Metastasis free survival will be assessed yearly by bone-scan after first PSA progression until the date of first documented metastasis on bone scan, date of death from any cause, whichever came first, assessed up to 100 months
|
From date of randomization until the date of first documented date of metastases, assessed yearly by bone-scan after first PSA_progression until first sign of metastasis, whichever came first, assessed up to 100 months
|
|
Difference between groups regarding overall survival
大体时间：From date of randomization until the date of death from any cause reported yearly by the study sites up to 100 months
|
Survival will be assessed yearly up to 100 months after inclusion
|
From date of randomization until the date of death from any cause reported yearly by the study sites up to 100 months
|
|
Difference between groups regarding cancer specific survival
大体时间：From date of randomization until date of death from prostate cancer,reported yearly by the study sites up to 100 months
|
Cancer specific survival will be assessed yearly up to 100 months after inclusion
|
From date of randomization until date of death from prostate cancer,reported yearly by the study sites up to 100 months
|
|
Measurement of grade of toxicity of given treatments
大体时间：At date of randomization, during treatment and follow up questionaries until 60 months
|
Adverse events recording using NCI-CTCAE (v3.0)
|
At date of randomization, during treatment and follow up questionaries until 60 months
|
合作者和调查者
调查人员
- 首席研究员：Andreas Josefsson, PhD、Univeristy of Gothenburg
- 首席研究员：Ingela Turesson, Prof、Uppsala University
出版物和有用的链接
有用的网址
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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