Prostate Cancer
Conditions
Brief summary
This clinical trial will determine whether the addition of radiotherapy to standard of care systemic therapy improves objective progression-free survival compared to systemic therapy alone in patients with oligometastatic castration-resistant prostate cancer.
Interventions
RADIATIONAblative Radiation Therapy
Radiotherapy will typically be delivered to a total EQD2 (Equivalent dose in 2Gy fractions) that ranges between conventional 30 Gy in 10 fractions, to SBRT (Stereotactic Body Radiation Therapy) with 50 Gy in 5 fractions.
DRUGHormone therapy or chemotherapy
Current standard of care dosing with standard agents; hormone therapy or chemotherapy.
Sponsors
University of Michigan Rogel Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must have biopsy-confirmed adenocarcinoma of the prostate * Subjects must discontinue any prior systemic therapies (excluding GnRH agonist/antagonists) without PSA withdrawal effects if using first generation anti-androgens. Luteinizing hormone-releasing hormone (LHRH) analogues must be continued if they have not undergone orchiectomy. (Subjects who recently started systemic therapy for metastatic castration-resistant prostate cancer (mCRPC) are eligible to enroll if new therapy was started ≤ 14 days to consent date.) * Subjects must have progressive metastatic castration-resistant prostate cancer based on at least one of the following criteria while having castrate levels (\<50 ng/dL) of testosterone: * A) PSA progression defined as a 25% increase over baseline value with an increase in the absolute value of at least 2.0 ng/mL that is confirmed by another PSA level with a minimum of a 1-week interval. * B) Progression of bidimensionally measurable soft tissue or nodal metastasis by CT scan or MRI based on RECIST criteria * C) Progression of bone disease on bone scan as defined by two new lesions arising * Subjects must have oligometastatic prostate cancer, defined as between 1 and ≤5 treatment sites that can be treated within a radiotherapy treatment field. * Subjects must be medically fit to undergo radiotherapy and systemic therapy as determined by the treating physician. * Age ≥ 18 * ECOG ≤ 2 (Eastern Cooperative Oncology Group scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 5 where 0 represents perfect health and 5 represents death) * No prior invasive malignancy in the past 3-years. Exceptions include non-melanomatous skin cancer and in situ cancers of the bladder or head and neck are permissible. * Subjects must freely sign informed consent to enroll in the study. * Subjects must use contraception up to 90 days after last drug dose.
Exclusion criteria
* Planned systemic therapy with Radium-223 dichloride or sipuleucel-T * Tumor requiring emergent radiation in view of provider * Life expectancy estimate of \<3 months * Presence of known parenchymal brain metastasis * Uncontrolled intercurrent illness * Inability to undergo radiotherapy, systemic treatment, CTs or bone scans * Biopsy proven pure small cell or neuroendocrine prostate cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Duration of Response | At 12 Months | Duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. A patient's designated response at any one time is a combination of the assessment of target lesions, non-target lesions, bone lesions and disease symptoms. Progression in this measure is defined as worsened pain or new sites of disease on imaging. Progression by pain due to prostate cancer requires evidence of disease at the site of pain and one or more palliative intervention (opioid therapy for 10 out of 14 consecutive days, radionuclide therapy or radiation therapy). Response and progression definitions used will be a combination of the criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee v1.1 and the Prostate Cancer Working Group 3. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Prostate Specific Antigen (PSA) PFS | At 24 months | The Median PSA PFS is defined as the median duration of time from start of treatment to date that PSA progression is documented or death occurs (whichever is first). PSA progression is defined as a 25% increase over baseline or nadir whichever is lower and an increase in the absolute value of PSA level by 2 ng/ml. Reported as Kaplan-Meier estimates, including median at 12 months and 24 month. |
| Median Radiographic PFS | At 24 months | Radiographic PFS is defined as the duration of time from start of treatment to date that progression is radio-graphically documented or death occurs (whichever is first). Reported as Kaplan-Meier estimates, including median at 12 months and 24 month. |
| Overall Survival Time | 24 months | Overall survival (OS) is defined as the duration of time from start of treatment to death. Reported as Kaplan-Meier estimates, including median at 12 months and 24 month. |
| Prostate Cancer Specific Survival Time | 24 months | Prostate Cancer Specific Survival (PCSS) is defined as the duration of time from start of treatment to death from prostate cancer. Reported as Kaplan-Meier estimates, including median at 12 months and 24 month. |
| Non-irradiated Metastases Free Survival Time | At 24 months | Non-irradiated metastases free survival is defined as the duration of time from start of treatment to the date of progressive disease of a new target lesion, a new non-measurable/non-target lesion or emergence of 2 or more new skeletal lesions on a bone scan. Reported as Kaplan-Meier estimates, including median at 12 months and 24 month. |
| Median Objective Progression Free Survival (PFS) Time | At 24 months | PFS is defined as the duration of time from start of treatment to date of progression or death (whichever is first). Initiation of other prostate directed therapies (excluding bisphosphonates or RANKL inhibitors) is considered to be progression. Reported as Kaplan-Meier estimates, including median at 12 months and 24 month. |
| The Proportion of Patients With a PSA Partial Response 50 (PR50) | 24 months | The number of patients whose PSA declines by 50% decline (PSA partial response 50 (PR50)) will be counted in each treatment arm and divided by the number of patients who received any protocol treatment to provide the proportion of patients with PR50. PR50 response is defined as a decrease in PSA value by ≥ 50%. |
| The Proportion of Patients With a PSA Partial Response 90 (PR90) | 24 months | The number of patients whose PSA declines by 90% decline (PSA partial response 90 (PR90)) will be counted in each treatment arm and divided by the number of patients who received any protocol treatment to provide the proportion of patients with PR90. PR90 response is defined as a decrease in PSA value by ≥ 90%. |
| The Proportion of Patients That Respond to Treatment | 24 months | The measurable disease response rate (CR + PR) will be calculated for patients evaluable for measurable disease response. Complete response (CR) is defined as a disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduced in short axis to \<10 mm. There can be no appearance of new lesions. Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions. |
| Patient-reported Outcome Based on NCCN-FACT FPSI-17 (Version 2) | measured at 6 and 12 months post starting treatment | The National Comprehensive Cancer Network Functional Assessment of Cancer Therapy - Prostate Symptom Index (NFPSI-17), version 2 is used to assess high priority symptoms/QOL concerns in patients with advanced prostate cancer (PC). It is a 17-item survey with a recall period of the past 7 days; scored using a 5 point Likert-type scale. Items are scored from 1-4 with some items reverse scored. Described using means or medians. score range is 0-68 with higher scores indicating better health |
| The Proportion of Patients With Complete PSA Response | 24 months | The number of patients whose PSA becomes undetectable (≤0.2 ng/ml) will be counted in each treatment arm and divided by the number of patients who received any protocol treatment to provide the proportion of patients with complete PSA response. Complete PSA response is defined as an undetectable PSA (≤0.2 ng/ml). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care Standard of care therapy will be up to the treating medical oncologist and is not the study intervention. Current systemic therapy is most commonly a second generation androgen pathway inhibitor, including enzalutamide or abiraterone, although other standard agents (e.g. docetaxel, cabazitaxel) are allowed. Patients should begin systemic treatment within 3 weeks of randomization. Standard of care systemic therapy may continue in the absence of toxicities or other specific criteria per protocol.
Hormone therapy or chemotherapy: Current standard of care dosing with standard agents; hormone therapy or chemotherapy. | 9 |
| Standard of Care + Ablative Radiation Standard of care systemic therapy plus radiation. Radiation will start within 8 weeks of randomization and complete by day 84. Standard of care systemic therapy may continue in the absence of toxicities or other specific criteria per protocol.
Ablative Radiation Therapy: Radiotherapy will typically be delivered to a total EQD2 (Equivalent dose in 2Gy fractions) that ranges between conventional 30 Gy in 10 fractions, to SBRT (Stereotactic Body Radiation Therapy) with 50 Gy in 5 fractions.
Hormone therapy or chemotherapy: Current standard of care dosing with standard agents; hormone therapy or chemotherapy. | 5 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease Progression after treatment started | 3 | 3 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Sponsor Termination | 2 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Standard of Care | Standard of Care + Ablative Radiation | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 2 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 5 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 4 Participants | 12 Participants |
| Region of Enrollment United States | 9 participants | 5 participants | 14 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 9 Participants | 5 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 9 | 2 / 5 |
| other Total, other adverse events | 9 / 9 | 5 / 5 |
| serious Total, serious adverse events | 3 / 9 | 0 / 5 |
Outcome results
Primary
Median Duration of Response
Duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. A patient's designated response at any one time is a combination of the assessment of target lesions, non-target lesions, bone lesions and disease symptoms. Progression in this measure is defined as worsened pain or new sites of disease on imaging. Progression by pain due to prostate cancer requires evidence of disease at the site of pain and one or more palliative intervention (opioid therapy for 10 out of 14 consecutive days, radionuclide therapy or radiation therapy). Response and progression definitions used will be a combination of the criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee v1.1 and the Prostate Cancer Working Group 3.
Time frame: At 12 Months
Population: NA- Per biostatistician, values must be reported as NA due to lack of data from insufficient number of participants with events. Data is not available now nor will it be available in the future
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care | Median Duration of Response | NA months |
| Standard of Care + Ablative Radiation | Median Duration of Response | NA months |
Secondary
Median Objective Progression Free Survival (PFS) Time
PFS is defined as the duration of time from start of treatment to date of progression or death (whichever is first). Initiation of other prostate directed therapies (excluding bisphosphonates or RANKL inhibitors) is considered to be progression. Reported as Kaplan-Meier estimates, including median at 12 months and 24 month.
Time frame: At 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care | Median Objective Progression Free Survival (PFS) Time | NA Months |
| Standard of Care + Ablative Radiation | Median Objective Progression Free Survival (PFS) Time | 26 Months |
Secondary
Median Prostate Specific Antigen (PSA) PFS
The Median PSA PFS is defined as the median duration of time from start of treatment to date that PSA progression is documented or death occurs (whichever is first). PSA progression is defined as a 25% increase over baseline or nadir whichever is lower and an increase in the absolute value of PSA level by 2 ng/ml. Reported as Kaplan-Meier estimates, including median at 12 months and 24 month.
Time frame: At 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care | Median Prostate Specific Antigen (PSA) PFS | NA months |
| Standard of Care + Ablative Radiation | Median Prostate Specific Antigen (PSA) PFS | NA months |
Secondary
Median Radiographic PFS
Radiographic PFS is defined as the duration of time from start of treatment to date that progression is radio-graphically documented or death occurs (whichever is first). Reported as Kaplan-Meier estimates, including median at 12 months and 24 month.
Time frame: At 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care | Median Radiographic PFS | NA Months |
| Standard of Care + Ablative Radiation | Median Radiographic PFS | 26 Months |
Secondary
Non-irradiated Metastases Free Survival Time
Non-irradiated metastases free survival is defined as the duration of time from start of treatment to the date of progressive disease of a new target lesion, a new non-measurable/non-target lesion or emergence of 2 or more new skeletal lesions on a bone scan. Reported as Kaplan-Meier estimates, including median at 12 months and 24 month.
Time frame: At 24 months
Population: NA- Per biostatistician, values must be reported as NA due to lack of data from insufficient number of participants with events. Data is not available now nor will it be available in the future
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care | Non-irradiated Metastases Free Survival Time | NA days |
| Standard of Care + Ablative Radiation | Non-irradiated Metastases Free Survival Time | NA days |
Secondary
Overall Survival Time
Overall survival (OS) is defined as the duration of time from start of treatment to death. Reported as Kaplan-Meier estimates, including median at 12 months and 24 month.
Time frame: 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care | Overall Survival Time | NA months |
| Standard of Care + Ablative Radiation | Overall Survival Time | NA months |
Secondary
Patient-reported Outcome Based on NCCN-FACT FPSI-17 (Version 2)
The National Comprehensive Cancer Network Functional Assessment of Cancer Therapy - Prostate Symptom Index (NFPSI-17), version 2 is used to assess high priority symptoms/QOL concerns in patients with advanced prostate cancer (PC). It is a 17-item survey with a recall period of the past 7 days; scored using a 5 point Likert-type scale. Items are scored from 1-4 with some items reverse scored. Described using means or medians. score range is 0-68 with higher scores indicating better health
Time frame: measured at 6 and 12 months post starting treatment
Population: score range is 0-68 with higher scores indicating better health
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Standard of Care | Patient-reported Outcome Based on NCCN-FACT FPSI-17 (Version 2) | 6 Months | 41.5 score on a scale |
| Standard of Care | Patient-reported Outcome Based on NCCN-FACT FPSI-17 (Version 2) | 12 Months | 41.8 score on a scale |
| Standard of Care + Ablative Radiation | Patient-reported Outcome Based on NCCN-FACT FPSI-17 (Version 2) | 6 Months | 39.1 score on a scale |
| Standard of Care + Ablative Radiation | Patient-reported Outcome Based on NCCN-FACT FPSI-17 (Version 2) | 12 Months | 39.7 score on a scale |
Secondary
Prostate Cancer Specific Survival Time
Prostate Cancer Specific Survival (PCSS) is defined as the duration of time from start of treatment to death from prostate cancer. Reported as Kaplan-Meier estimates, including median at 12 months and 24 month.
Time frame: 24 months
Population: NA- Per biostatistician, values must be reported as NA due to lack of data from insufficient number of participants with events. Data is not available now nor will it be available in the future
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care | Prostate Cancer Specific Survival Time | NA days |
| Standard of Care + Ablative Radiation | Prostate Cancer Specific Survival Time | NA days |
Secondary
The Proportion of Patients That Respond to Treatment
The measurable disease response rate (CR + PR) will be calculated for patients evaluable for measurable disease response. Complete response (CR) is defined as a disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduced in short axis to \<10 mm. There can be no appearance of new lesions. Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | The Proportion of Patients That Respond to Treatment | 22 percentage of patients |
| Standard of Care + Ablative Radiation | The Proportion of Patients That Respond to Treatment | 20 percentage of patients |
Secondary
The Proportion of Patients With a PSA Partial Response 50 (PR50)
The number of patients whose PSA declines by 50% decline (PSA partial response 50 (PR50)) will be counted in each treatment arm and divided by the number of patients who received any protocol treatment to provide the proportion of patients with PR50. PR50 response is defined as a decrease in PSA value by ≥ 50%.
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | The Proportion of Patients With a PSA Partial Response 50 (PR50) | 89 percentage of patients |
| Standard of Care + Ablative Radiation | The Proportion of Patients With a PSA Partial Response 50 (PR50) | 60 percentage of patients |
Secondary
The Proportion of Patients With a PSA Partial Response 90 (PR90)
The number of patients whose PSA declines by 90% decline (PSA partial response 90 (PR90)) will be counted in each treatment arm and divided by the number of patients who received any protocol treatment to provide the proportion of patients with PR90. PR90 response is defined as a decrease in PSA value by ≥ 90%.
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | The Proportion of Patients With a PSA Partial Response 90 (PR90) | 44 percentage of patients |
| Standard of Care + Ablative Radiation | The Proportion of Patients With a PSA Partial Response 90 (PR90) | 60 percentage of patients |
Secondary
The Proportion of Patients With Complete PSA Response
The number of patients whose PSA becomes undetectable (≤0.2 ng/ml) will be counted in each treatment arm and divided by the number of patients who received any protocol treatment to provide the proportion of patients with complete PSA response. Complete PSA response is defined as an undetectable PSA (≤0.2 ng/ml).
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | The Proportion of Patients With Complete PSA Response | 67 percentage of patients |
| Standard of Care + Ablative Radiation | The Proportion of Patients With Complete PSA Response | 40 percentage of patients |