A Phase 2 Trial of Radium Ra 223 Dichloride in Combination With Androgen Deprivation Therapy and Stereotactic Body Radiation Therapy for Patients With Oligometastatic Castration Sensitive Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Objective response rate
研究概览
简要总结
This phase 2 trial studies radium Ra 223 dichloride, hormone therapy and stereotactic body radiation in treating patients with prostate cancer that has spread to other places in the body. Radium Ra 223 dichloride contains a radioactive substance that collects in the bone and gives off radiation that may kill cancer cells. Hormone therapy using leuprolide acetate or goserelin acetate may fight prostate cancer by lowering the amount of testosterone the body makes. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Giving radium Ra 223 dichloride, hormone therapy and stereotactic body radiation may work better at treating prostate cancer.
详细描述
PRIMARY OBJECTIVES:
I. To assess the time to treatment failure (TTF) in patients who initiated the protocol regimen of androgen deprivation therapy (ADT) with stereotactic body radiation therapy (SBRT) and radium Ra 223 dichloride and received at least one dose with radium Ra 223 dichloride.
SECONDARY OBJECTIVES:
I. To assess the safety of adding radium Ra 223 dichloride to SBRT and ADT in patients with oligometastatic castration sensitive prostate cancer.
II. To assess the prostate-specific antigen (PSA) and overall response rate (ORR) after 6 cycles of radium Ra 223 dichloride (cycle 8 day 1).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented informed consent of participant and/or legally authorized representative
- •Agreement to provide archival primary or metastatic tumor tissue if available
- •Eastern Cooperative Oncology Group (ECOG) =< 2
- •Life expectancy > 12 months
- •Histologic diagnosis of prostate adenocarcinoma
- •* Pure small cell carcinoma will be excluded; however, component of neuroendocrine /small cell differentiation will be allowed provided that adenocarcinoma constitutes majority of the tissue specimen
- •* Metastatic disease can be documented by bone scan or computed tomography (CT) scan or magnetic resonance imaging (MRI) or positron emission tomography (PET)/CT or the combination of these tests
- •Up to 4 metastatic lesions:
- •Must have at least 1 bone lesion AND each non-visceral lesion should be less than 5 cm
- •Visceral lesions will be limited to one lung lesion (< 2 cm) or one lymph node; no liver lesions allowed; lymph nodes allowed provided they are not in a field of prior radiation, and if amenable to SBRT (to be reviewed by principal investigator [PI])
- •Two lesions can be in close proximity (i.e. within 5 cm of each other) if they meet radiation SBRT normal tissue toxicity requirements
- •If have untreated primary prostate cancer: must undergo debulking prostatectomy
- •If had prior definitive radiation therapy to the prostate: no evidence of locally persistent or recurrent prostate cancer on digital rectal exam (DRE) and imaging studies (CT or MRI); retreatment to local residual-recurrent disease will result in potential eligibility to be reviewed by PI on a case-by-case basis
- •Does not have castration resistant disease
- •* Castration resistance defined as progression of disease despite serum testosterone level of < 50 ng/dL
- •PSA >= 0.2 prior to start of androgen deprivation treatment
- •Initiated 28 (+ 7) days of androgen deprivation therapy (ADT) prior to day 1 of protocol therapy
- •* Only luteinizing hormone-releasing hormone (LHRH) agonist/antagonist treatment is considered ADT, bicalutamide or other antiandrogens used alone do not count
- •May have received prior hormonal therapy in the context of definitive treatment of a primary tumor
- •* Patients may have had one prior systemic non-chemotherapeutic treatment (i.e. immunotherapy, receptor tyrosine kinase inhibitor, antiangiogenic agent, differentiating agent) for recurrent or metastatic disease
- •Must have refused standard of care chemotherapy for metastatic disease
- •Recovered from all acute side-effects (except alopecia) related to previous systemic therapy
- •Absolute neutrophil count (ANC) >= 1,500/mm^3 (to be performed within 14 days prior to day 1 of protocol therapy)
- •* NOTE: growth factor support is not permitted to normalize baseline ANC parameters, however subsequent growth factor administration is permitted as standard supportive care
- •Platelets >= 100,000/mm^3 (to be performed within 14 days prior to day 1 of protocol therapy)
- •* NOTE: transfusion of blood products are not allowed to normalize baseline blood parameters, however subsequent transfusions are allowed per standard supportive care guidelines
- •Hemoglobin (HgB) >= 9.0 g/dL (to be performed within 14 days prior to day 1 of protocol therapy)
- •* NOTE: transfusion of blood products are not allowed to normalize baseline blood parameters, however subsequent transfusions are allowed per standard supportive care guidelines
- •Total serum bilirubin =< 2 x upper limit of normal (ULN) (to be performed within 14 days prior to day 1 of protocol therapy)
- •Aspartate aminotransferase (AST) =< 2.5 x ULN (to be performed within 14 days prior to day 1 of protocol therapy)
- •Alanine aminotransferase (ALT) =< 2.5 x ULN (to be performed within 14 days prior to day 1 of protocol therapy)
- •Creatinine =< 2.5 mg/dL (to be performed within 14 days prior to day 1 of protocol therapy)
排除标准
- •Prior radium Ra 223 dichloride
- •Prior or concomitant chemotherapy for metastatic or recurrent disease with the following exceptions:
- •Prior chemotherapy for local primary disease is permitted
- •Bisphosphonates or receptor activator of nuclear factor kappa-Β (RANK) ligand inhibitors are allowed at doses and schedule consistent with the treatment or prevention of osteoporosis
- •Prior radiation treatment for metastatic disease
- •Concomitant radiation treatment to primary prostate site
- •Orchiectomy
- •Unstable medical comorbidities (i.e. uncontrolled cardiac comorbidities)
- •Metastases that in the judgment of investigator-radiologist are not amenable to SBRT
- •History of brain metastases or who currently have treated or untreated brain metastases
- •Uncontrolled human immunodeficiency virus (HIV) infection
- •Any other condition that would, in the investigator's judgement, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
研究组 & 干预措施
Treatment (hormone therapy, SBRT, radium Ra 223 dichloride)
Beginning 4 weeks (28 days) prior to radiation therapy, patients receive leuprolide acetate or goserelin acetate, for up to 32 weeks. Patients also undergo 3-5 fractions of SBRT every 40 hours over 7-21 days beginning on day 1 of course 1, and receive radium Ra 223 dichloride IV over 1 minute on day 1 of courses 2-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Stereotactic Body Radiation Therapy (Radiation)
Treatment (hormone therapy, SBRT, radium Ra 223 dichloride)
Beginning 4 weeks (28 days) prior to radiation therapy, patients receive leuprolide acetate or goserelin acetate, for up to 32 weeks. Patients also undergo 3-5 fractions of SBRT every 40 hours over 7-21 days beginning on day 1 of course 1, and receive radium Ra 223 dichloride IV over 1 minute on day 1 of courses 2-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Degarelix (Drug)
Treatment (hormone therapy, SBRT, radium Ra 223 dichloride)
Beginning 4 weeks (28 days) prior to radiation therapy, patients receive leuprolide acetate or goserelin acetate, for up to 32 weeks. Patients also undergo 3-5 fractions of SBRT every 40 hours over 7-21 days beginning on day 1 of course 1, and receive radium Ra 223 dichloride IV over 1 minute on day 1 of courses 2-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Radium Ra 223 Dichloride (Radiation)
Treatment (hormone therapy, SBRT, radium Ra 223 dichloride)
Beginning 4 weeks (28 days) prior to radiation therapy, patients receive leuprolide acetate or goserelin acetate, for up to 32 weeks. Patients also undergo 3-5 fractions of SBRT every 40 hours over 7-21 days beginning on day 1 of course 1, and receive radium Ra 223 dichloride IV over 1 minute on day 1 of courses 2-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (hormone therapy, SBRT, radium Ra 223 dichloride)
Beginning 4 weeks (28 days) prior to radiation therapy, patients receive leuprolide acetate or goserelin acetate, for up to 32 weeks. Patients also undergo 3-5 fractions of SBRT every 40 hours over 7-21 days beginning on day 1 of course 1, and receive radium Ra 223 dichloride IV over 1 minute on day 1 of courses 2-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Leuprolide Acetate (Drug)
Treatment (hormone therapy, SBRT, radium Ra 223 dichloride)
Beginning 4 weeks (28 days) prior to radiation therapy, patients receive leuprolide acetate or goserelin acetate, for up to 32 weeks. Patients also undergo 3-5 fractions of SBRT every 40 hours over 7-21 days beginning on day 1 of course 1, and receive radium Ra 223 dichloride IV over 1 minute on day 1 of courses 2-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Goserelin Acetate (Drug)
结局指标
主要结局
Objective response rate
时间窗: Up to 5 years
Response will be evaluated in this study using modified Prostate Cancer Working Group 2 criteria. Proportion of patients achieving complete response (CR) or partial response (PR) at course 8, day 1 (post 6 doses of radium Ra 223 dichloride).
Time to treatment failure
时间窗: Assessed up to 5 years
Defined as time from the initiation of androgen deprivation therapy (ADT) for metastatic disease until PSA increase to \> pre-ADT level or PSA \> 10 (whichever is smaller) or radiographic or clinical progression or resumption of ADT by physician's choice.
Time to Treatment Failure
时间窗: Assessed up to 5 years
Defined as time from the initiation of androgen deprivation therapy (ADT) for metastatic disease until PSA increase to \> pre-ADT level or PSA \> 10 (whichever is smaller) or radiographic or clinical progression or resumption of ADT by physician's choice.
Objective Response Rate
时间窗: Up to 5 years
Response will be evaluated in this study using the modified Prostate Cancer Working Group 2 criteria. Per Prostate Cancer Working Group 2 criteria for target lesions: Complete Response (CR), Disappearance of all target lesions. Lymph node CR is when the lymph node has decreased to less than 10mm in the short axis; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; For non-target lesions, CR: Disappearance of all non-target lesions and PSA level \<0.04 (undetectable). Overall Response (OR) = CR + PR. Proportion of patients achieving CR or PR at course 8, day 1 (post 6 doses of radium Ra 223 dichloride) were reported.
次要结局
- Progression-free survival(From the initiation of ADT for metastatic disease until PSA progression or radiographic progression or death, assessed up to 5 years)
- Overall survival(From date of initiation of protocol treatment to date of death from any cause, assessed up to 5 years)
- Complete response (CR) rate defined as the proportion of patients achieving CR(Up to 5 years)
- Duration of response(From documented response to recurrent or progressive disease is first met, assessed up to 5 years)
- Duration of overall complete response(From documented CR to recurrent/ progressive disease, assessed up to 5 years)
- Bone specific progression-free survival(Time to progression of bone specific disease over baseline, assessed up to 5 years)
- Duration of stable disease(Time from start of treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, assessed up to 5 years)
- Incidence of adverse events (AE) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0(Up to 5 years)
- Progression-free Survival(From the initiation of ADT for metastatic disease until PSA progression or radiographic progression or death, assessed up to 5 years)
- Overall Survival(From date of initiation of protocol treatment to date of death from any cause, assessed up to 5 years)
- Complete Response (CR) Rate Defined as the Proportion of Patients Achieving CR(Up to 5 years)
- Duration of Response(From documented response to recurrent or progressive disease is first met, assessed up to 5 years)
- Duration of Overall Complete Response(From documented CR to recurrent/ progressive disease, assessed up to 5 years)
- Bone Specific Progression-free Survival(Time to progression of bone specific disease over baseline, assessed up to 5 years)
- Duration of Stable Disease(Time from start of treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, assessed up to 5 years)
- Number of Participants With Adverse Events (AE) Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0(Up to 5 years)