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

Overview

This clinical trial will determine whether the addition of radiotherapy to standard of care early systemic therapy improves objective progression-free survival rate (combined radiographic and clinical) at 18 months, compared to systemic therapy alone in patients with oligometastatic castration-resistant prostate cancer.

Full Title of Study: “FOcal Radiation for Oligometastatic Castration-rEsistant Prostate Cancer (FORCE): A Phase II Randomized Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 1, 2022

Interventions

  • Radiation: Radiation Therapy
    • Radiotherapy will be delivered to a total EQD2 (Equivalent dose in 2Gy fractions) that ranges between conventional 30 Gy in 10 fractions, to SBRT with 50 Gy in 5 fractions.
  • Drug: Enzalutamide
    • Current standard of care dosing
  • Drug: Abiraterone
    • Current standard of care dosing
  • Drug: Docetaxel
    • Current standard of care dosing

Arms, Groups and Cohorts

  • Active Comparator: Standard of Care
    • The choice of agent will be up to the treating medical oncologist and is not the study intervention. Current first line systemic therapy is most commonly a second generation androgen pathway inhibitor, including enzalutamide or abiraterone, although docetaxel is allowed. Patients should begin systemic treatment within 3 weeks of randomization.
  • Experimental: Standard of Care + Radiotherapy
    • 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 docetaxel is allowed. Radiotherapy will 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. Patients should start systemic therapy within 3 weeks of randomization (unless radiation is begun within 3 weeks and the provider may hold systemic therapy until completion of radiation) and receive radiotherapy within 8 weeks of randomization.

Clinical Trial Outcome Measures

Primary Measures

  • The proportion of patients who are progression-free and alive at 18 months
    • Time Frame: 18 Months
    • The number of patients who are objective progression-free and alive at 18 months will be counted in each treatment arm and divided by the number of patients who received any protocol treatment to provide the 18-month objective PFS (progression free survival) proportion. 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. For target/measurable disease progression will be defined as at least a 20% increase in the sum of the LD (longest diameter) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new target lesions is also considered progression.

Secondary Measures

  • Median objective progression free survival time
    • Time Frame: 24 months
    • Objective progression-free survival (PFS) is defined as the duration of time from start of treatment to date that progression is objectively documented or death occurs (whichever is first).
  • Median PSA progression free survival time
    • Time Frame: Up to 24 months
    • The Median PSA progression free survival time 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 (prostate specific antigen) 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.
  • Median radiographic progression free survival
    • Time Frame: 24 months
    • Radiographic progression-free survival (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).
  • Overall survival time
    • Time Frame: 24 months
    • Overall survival (OS) is defined as the duration of time from start of treatment to death.
  • Prostate cancer specific survival time
    • Time Frame: 24 months
    • Prostate Cancer Specific Survival (PCSS) is defined as the duration of time from start of treatment to death from prostate cancer.
  • Non-irradiated metastases free survival time
    • Time Frame: 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.
  • The proportion of patients with complete PSA response
    • Time Frame: Up to 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).
  • The proportion of patients with a PSA Partial Response 50 (PR50)
    • Time Frame: Up to 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)
    • Time Frame: Up to 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
    • Time Frame: 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.

Participating in This Clinical Trial

Inclusion Criteria

  • Subjects must have biopsy-confirmed adenocarcinoma of the prostate
  • Subjects must discontinue all systemic or experimental therapies started for metastatic hormone-sensitive prostate cancer (mHSPC) for at least 2 weeks prior to registration with no evidence of a falling PSA (prostate specific antigen) after washout. LHRH (luteinizing hormone-releasing hormone) 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 unless disease free for a minimum of 2 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
  • 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

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Michigan Rogel Cancer Center
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Zachery Reichert, MD, PhD, Principal Investigator, University of Michigan Rogel Cancer Center
  • Overall Contact(s)
    • Zachery Reichert, MD, PhD, (734)-764-3066, zreiche@med.umich.edu

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