Long-term Effects of Enhanced Systemic Therapy and Tumor-directed Therapy for Newly Diagnosed Oligometastatic Prostate Cancer Confirmed by Conventional Imaging Modality: a Prospective, Single-arm Study.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Two years' radiographic progression-free survival (rPFS)
研究概览
简要总结
Oligo-metastatic prostate cancer (OMPCa) is considered as an intermediated state between localized and poly-metastatic disease. Various retrospective studies and prospective clinical trials are carrying out to validate whether patients with OMPCa could benefit from local treatment for both primary and metastatic lesions. The investigators here to conduct a unique clinical trial which OMPCa patients were confirmed by conventional imaging, and received a long-term enhanced systemic therapy accompanied by tumor-directed therapy.
详细描述
Recent studies showed that metastatic lesion of prostate cancer may originate from both the primary and the existing metastatic lesion, thus, disease with limited number of metastatic lesions were considered as oligo-metastatic prostate cancer (OMPCa), an intermediated state between localized and poly-metastatic disease. For patients with newly diagnosed OMPCa, serval studies revealed that prostate radiation therapy could improve their clinical outcomes. For patients with oligo-recurrent prostate cancer, they could also be benefit from stereotactic ablative radiation therapy to the metastatic lesion. The investigators thus designed a distinct clinical trial including patients who were confirmed as oligo-metastatic disease by conventional imaging modality (CT, MRI and ECT) rather than PSMA PET-CT. This study also aimed to evaluate the therapeutic effects of tumor-directed treatment under the background of long-term enhanced systemic therapy, including abiraterone, enzalutamide or apalutamide. Here, the investigators proposed that, for patients with de novo oligo-metastatic prostate cancer, enhanced systemic treatment combined with radical treatment of primary lesion and radiotherapy of all accessible metastatic lesions may prolong their survival time without affecting their quality of life.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed de novo prostate adenocarcinoma (can be accompanied by neuroendocrine differentiation, but accounts for less than 10% of the total tumor components);
- •Aged between 18 and 80;
- •M1a/b disease with presence of 1-5 visible metastases (detected by bone scan (ECT), chest, abdominal and pelvic CT or MRI). Biopsy of the suspected metastases is recommended to the patients. If the patients refused to the biopsy, additional PSMA-PET/CT or regional MRI should be performed to confirm the metastatic lesions.
- •The metastatic lesions should meet the following the criteria:
- •Metastases are limited to bone or lymph nodes;
- •Visceral metastases are not allowed;
- •Radiographic observed pelvic lymph node metastasis with a diameter of >2cm should also be considered as one metastatic lesion.
- •If the lymph nodes are the only detected metastatic lesions, at least one metastatic lymph node should be outside the pelvis.
- •ECOG performance status of 0 or 1;
- •PSA less than 100ng/ml at diagnosis;
- •No more than one month's systemic treatment before enrollment (including castration (surgical or medical castration), castration combined with traditional anti-androgen therapy (flutamide or bicalutamide));
- •No previous pelvic radiotherapy history;
- •The primary lesion of prostate cancer has not received any form of local treatment (surgery, radiotherapy, cryotherapy, radiofrequency ablation, etc.); TURP is allowed, if the aim of the surgery is to relieve lower urinary tract symptom but not to treat the tumor.
- •The metastatic lesions of prostate cancer have not received any form of local treatment (surgery, radiotherapy, cryotherapy, radiofrequency ablation, etc.);
- •Written informed consent;
- •Willing and expected to comply with treatment and follow up schedule.
- •Life expectancy > 10 years.
排除标准
- •Received prior local treatment for primary lesion or metastatic lesions, including radical prostatectomy, radical radiotherapy, surgery or radiotherapy to metastatic lesion;
- •Received prior systemic treatment for prostate cancer longer than 1 month;
- •Received prior castration combined with new-generation androgen signaling pathway inhibitors such as abiraterone, apalutamide or enzalutamide; castration combined with docetaxel chemotherapy;
- •Had any visceral metastases (liver, lung, brain etc.);
- •Histologically or cytologically confirmed small cell carcinoma;
- •Unable to tolerate the treatment for primary and metastatic lesion;
- •Unwilling to accept potential related adverse events caused by treatment for primary and metastatic lesion;
- •Had any other previous or current malignant disease, except for curatively treated skin basal cell carcinoma or other tumors cured for more than 5 years;
- •Had other severe disorders, such as:
- •Unstable cardiac disease,
- •Myocardial infarction less than 6 months prior to enrollment,
- •Clinically significant cardiac failure requiring treatment, defined as New York Heart Association (NYHA) class III,
- •Uncontrolled hypertension,
- •Severe neurological or psychological disorder including dementia or epilepsy,
- •Uncontrolled active infection,
- •Acute gastric ulcer,
- •Hypercalcemia,
- •Chronic obstructive pulmonary lung disease requiring hospitalization,
- •Any other significant disorders that in the investigator's opinion means the participant is unfit for any of the study treatments;
- •Had participated in other clinical trial before enrollment.
- •Had contraindications to radiotherapy or unsuitable for radical radiotherapy evaluated by radiologists and physicists.
研究组 & 干预措施
systemic treatment combined with radical treatment and radiotherapy
All recruited participants would receive long-term and unified systemic treatment. Systemic treatment is defined as chemical castration plus new-generation anti-androgen therapy.
For the primary lesion:
The preferred local treatment for primary lesion is radical prostatectomy. Patients who refuse surgery or whose tumors cannot be surgically resected after 3 months' systemic treatment could receive radical radiotherapy.
For the metastatic lesion:
Radiotherapy for metastatic lesions would be performed between 4 weeks and 24 weeks after the local treatment for primary lesion. Stereotactic body radiation therapy (SBRT) is preferred, which could treat all the detected lesions at once or in stages.
干预措施: Leuprolide acetate (Drug)
systemic treatment combined with radical treatment and radiotherapy
All recruited participants would receive long-term and unified systemic treatment. Systemic treatment is defined as chemical castration plus new-generation anti-androgen therapy.
For the primary lesion:
The preferred local treatment for primary lesion is radical prostatectomy. Patients who refuse surgery or whose tumors cannot be surgically resected after 3 months' systemic treatment could receive radical radiotherapy.
For the metastatic lesion:
Radiotherapy for metastatic lesions would be performed between 4 weeks and 24 weeks after the local treatment for primary lesion. Stereotactic body radiation therapy (SBRT) is preferred, which could treat all the detected lesions at once or in stages.
干预措施: Goserelin acetate (Drug)
systemic treatment combined with radical treatment and radiotherapy
All recruited participants would receive long-term and unified systemic treatment. Systemic treatment is defined as chemical castration plus new-generation anti-androgen therapy.
For the primary lesion:
The preferred local treatment for primary lesion is radical prostatectomy. Patients who refuse surgery or whose tumors cannot be surgically resected after 3 months' systemic treatment could receive radical radiotherapy.
For the metastatic lesion:
Radiotherapy for metastatic lesions would be performed between 4 weeks and 24 weeks after the local treatment for primary lesion. Stereotactic body radiation therapy (SBRT) is preferred, which could treat all the detected lesions at once or in stages.
干预措施: Triptorelin acetate (Drug)
systemic treatment combined with radical treatment and radiotherapy
All recruited participants would receive long-term and unified systemic treatment. Systemic treatment is defined as chemical castration plus new-generation anti-androgen therapy.
For the primary lesion:
The preferred local treatment for primary lesion is radical prostatectomy. Patients who refuse surgery or whose tumors cannot be surgically resected after 3 months' systemic treatment could receive radical radiotherapy.
For the metastatic lesion:
Radiotherapy for metastatic lesions would be performed between 4 weeks and 24 weeks after the local treatment for primary lesion. Stereotactic body radiation therapy (SBRT) is preferred, which could treat all the detected lesions at once or in stages.
干预措施: Degarelix acetate (Drug)
systemic treatment combined with radical treatment and radiotherapy
All recruited participants would receive long-term and unified systemic treatment. Systemic treatment is defined as chemical castration plus new-generation anti-androgen therapy.
For the primary lesion:
The preferred local treatment for primary lesion is radical prostatectomy. Patients who refuse surgery or whose tumors cannot be surgically resected after 3 months' systemic treatment could receive radical radiotherapy.
For the metastatic lesion:
Radiotherapy for metastatic lesions would be performed between 4 weeks and 24 weeks after the local treatment for primary lesion. Stereotactic body radiation therapy (SBRT) is preferred, which could treat all the detected lesions at once or in stages.
干预措施: Abiraterone acetate (Drug)
systemic treatment combined with radical treatment and radiotherapy
All recruited participants would receive long-term and unified systemic treatment. Systemic treatment is defined as chemical castration plus new-generation anti-androgen therapy.
For the primary lesion:
The preferred local treatment for primary lesion is radical prostatectomy. Patients who refuse surgery or whose tumors cannot be surgically resected after 3 months' systemic treatment could receive radical radiotherapy.
For the metastatic lesion:
Radiotherapy for metastatic lesions would be performed between 4 weeks and 24 weeks after the local treatment for primary lesion. Stereotactic body radiation therapy (SBRT) is preferred, which could treat all the detected lesions at once or in stages.
干预措施: Apalutamide (Drug)
systemic treatment combined with radical treatment and radiotherapy
All recruited participants would receive long-term and unified systemic treatment. Systemic treatment is defined as chemical castration plus new-generation anti-androgen therapy.
For the primary lesion:
The preferred local treatment for primary lesion is radical prostatectomy. Patients who refuse surgery or whose tumors cannot be surgically resected after 3 months' systemic treatment could receive radical radiotherapy.
For the metastatic lesion:
Radiotherapy for metastatic lesions would be performed between 4 weeks and 24 weeks after the local treatment for primary lesion. Stereotactic body radiation therapy (SBRT) is preferred, which could treat all the detected lesions at once or in stages.
干预措施: Enzalutamide (Drug)
systemic treatment combined with radical treatment and radiotherapy
All recruited participants would receive long-term and unified systemic treatment. Systemic treatment is defined as chemical castration plus new-generation anti-androgen therapy.
For the primary lesion:
The preferred local treatment for primary lesion is radical prostatectomy. Patients who refuse surgery or whose tumors cannot be surgically resected after 3 months' systemic treatment could receive radical radiotherapy.
For the metastatic lesion:
Radiotherapy for metastatic lesions would be performed between 4 weeks and 24 weeks after the local treatment for primary lesion. Stereotactic body radiation therapy (SBRT) is preferred, which could treat all the detected lesions at once or in stages.
干预措施: Local treatment for primary lesion (Procedure)
systemic treatment combined with radical treatment and radiotherapy
All recruited participants would receive long-term and unified systemic treatment. Systemic treatment is defined as chemical castration plus new-generation anti-androgen therapy.
For the primary lesion:
The preferred local treatment for primary lesion is radical prostatectomy. Patients who refuse surgery or whose tumors cannot be surgically resected after 3 months' systemic treatment could receive radical radiotherapy.
For the metastatic lesion:
Radiotherapy for metastatic lesions would be performed between 4 weeks and 24 weeks after the local treatment for primary lesion. Stereotactic body radiation therapy (SBRT) is preferred, which could treat all the detected lesions at once or in stages.
干预措施: Radiotherapy for primary lesion (Radiation)
systemic treatment combined with radical treatment and radiotherapy
All recruited participants would receive long-term and unified systemic treatment. Systemic treatment is defined as chemical castration plus new-generation anti-androgen therapy.
For the primary lesion:
The preferred local treatment for primary lesion is radical prostatectomy. Patients who refuse surgery or whose tumors cannot be surgically resected after 3 months' systemic treatment could receive radical radiotherapy.
For the metastatic lesion:
Radiotherapy for metastatic lesions would be performed between 4 weeks and 24 weeks after the local treatment for primary lesion. Stereotactic body radiation therapy (SBRT) is preferred, which could treat all the detected lesions at once or in stages.
干预措施: Radiotherapy for metastatic lesion (Radiation)
结局指标
主要结局
Two years' radiographic progression-free survival (rPFS)
时间窗: 2 years
Proportion of patients without radiographic progression after two years' treatment. The soft-tissue lesion evaluation criterion was RECIST1.1, and the bone lesion evaluation criterion was PCWG3
次要结局
- Pathological complete response (pCR) or minimal residual disease (MRD) rate(1 month after prostatectomy as local treatment for primary lesion.)
- Two years' PSA progression-free survival (PSA-PFS)(2 years)
- Two years' overall survival (OS)(2 years)