Clinical Trials /

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

NCT03556904

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2017.163
  • SECONDARY ID: HUM00138918
  • NCT ID: NCT03556904

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
EnzalutamideStandard of Care
AbirateroneStandard of Care
DocetaxelStandard of Care

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Standard of CareActive ComparatorThe 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.
  • Enzalutamide
  • Abiraterone
  • Docetaxel
Standard of Care + RadiotherapyExperimentalStandard 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.
  • Enzalutamide
  • Abiraterone
  • Docetaxel

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:The proportion of patients who are progression-free and alive at 18 months
Time Frame:18 Months
Safety Issue:
Description: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 Outcome Measures

Measure:Median objective progression free survival time
Time Frame:24 months
Safety Issue:
Description: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).
Measure:Median PSA progression free survival time
Time Frame:Up to 24 months
Safety Issue:
Description: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.
Measure:Median radiographic progression free survival
Time Frame:24 months
Safety Issue:
Description: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).
Measure:Overall survival time
Time Frame:24 months
Safety Issue:
Description:Overall survival (OS) is defined as the duration of time from start of treatment to death.
Measure:Prostate cancer specific survival time
Time Frame:24 months
Safety Issue:
Description:Prostate Cancer Specific Survival (PCSS) is defined as the duration of time from start of treatment to death from prostate cancer.
Measure:Non-irradiated metastases free survival time
Time Frame:24 months
Safety Issue:
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.
Measure:The proportion of patients with complete PSA response
Time Frame:Up to 24 months
Safety Issue:
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).
Measure:The proportion of patients with a PSA Partial Response 50 (PR50)
Time Frame:Up to 24 months
Safety Issue:
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%.
Measure:The proportion of patients with a PSA Partial Response 90 (PR90)
Time Frame:Up to 24 months
Safety Issue:
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%.
Measure:The proportion of patients that respond to treatment
Time Frame:24 months
Safety Issue:
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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

Last Updated

October 9, 2019