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FOcal Radiation for Oligometastatic Castration-rEsistant Prostate Cancer (FORCE)

Primary Purpose

Prostate Cancer

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ablative Radiation Therapy
Hormone therapy or chemotherapy
Sponsored by
University of Michigan Rogel Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • VA Ann Arbor Healthcare System
  • University of Michigan Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard of Care

Standard of Care + Ablative Radiation

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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).
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%.
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%.
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.
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.

Full Information

First Posted
March 16, 2018
Last Updated
October 28, 2022
Sponsor
University of Michigan Rogel Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT03556904
Brief Title
FOcal Radiation for Oligometastatic Castration-rEsistant Prostate Cancer (FORCE)
Official Title
FOcal Radiation for Oligometastatic Castration-rEsistant Prostate Cancer (FORCE): A Phase II Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 10, 2018 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard of Care
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Standard of Care + Ablative Radiation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
Ablative Radiation Therapy
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Hormone therapy or chemotherapy
Other Intervention Name(s)
enzalutamide, abiraterone, docetaxel, cabazitaxel
Intervention Description
Current standard of care dosing with standard agents; hormone therapy or chemotherapy.
Primary Outcome Measure Information:
Title
Median duration of response
Description
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 and at 18 Months
Secondary Outcome Measure Information:
Title
Median objective progression free survival (PFS) time
Description
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 12 and at 24 months
Title
Median prostate specific antigen (PSA) PFS
Description
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 12 and at 24 months
Title
Median radiographic PFS
Description
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 12 and at 24 months
Title
Overall survival time
Description
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
At 12 and at 24 months
Title
Prostate cancer specific survival time
Description
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
At 12 and at 24 months
Title
Non-irradiated metastases free survival time
Description
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 12 and at 24 months
Title
The proportion of patients with complete PSA response
Description
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
Title
The proportion of patients with a PSA Partial Response 50 (PR50)
Description
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
Title
The proportion of patients with a PSA Partial Response 90 (PR90)
Description
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
Title
The proportion of patients that respond to treatment
Description
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
Title
Patient-reported outcome based on NCCN-FACT FPSI-17 (version 2)
Description
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.
Time Frame
24 months

10. Eligibility

Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zachery Reichert, MD, PhD
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Ann Arbor Healthcare System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
University of Michigan Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

FOcal Radiation for Oligometastatic Castration-rEsistant Prostate Cancer (FORCE)

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