External Beam Radiotherapy in Treating Participants with Metastatic Castration-Resistant Prostate Cancer
This phase II trial studies how well the addition of radiotherapy to standard of care works in treating participants with castration-resistant prostate cancer that has spread to other places in the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors.
Inclusion Criteria
- Subjects must have biopsy-confirmed adenocarcinoma of the prostate (pure small cell or pure neuroendocrine prostate cancer are not allowed)
- Patients must discontinue all systemic or experimental therapies (e.g. flutamide, bicalutamide, nilutamide, abiraterone, enzalutamide) for at least 2 weeks prior to registration with no evidence of a falling PSA after washout. LHRH analogues (agonist or antagonist) must be continued if they have not undergone orchiectomy
- 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: * 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 * Progression of bidimensionally measurable soft tissue or nodal metastasis by CT scan or magnetic resonance imaging (MRI) based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria * 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. All sites must be =< 5 cm in maximum cross section and prior radiation to a metastatic site must not preclude them from having a second full course of radiotherapy, unless that site was treated within 4 weeks of registration. Each site treated within four weeks of randomization are included in the total site count. These recently radiated patients must have at least 1 non-irradiated site remaining though to enroll * Examples: 2 adjacent vertebral bodies would count as 1 treatment site, multiple contiguous external iliac lymph nodes (LNs) would count as 1 treatment site, and untreated/intact prostate would count as 1 site. Also, a single symptomatic lesion that required treatment before enrollment would count as 1 site
- Subjects must be medically fit to undergo radiotherapy and first line systemic therapy as determined by the treating physician
- Eastern Cooperative Oncology Group (ECOG) =< 2
- 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
Exclusion Criteria
- Planned first line 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 including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements. This will be determined by one of the study principal investigators (PI)s if in question
- Inability to undergo radiotherapy, systemic treatment, CTs or bone scans
- Biopsy proven pure small cell or neuroendocrine prostate cancer
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03556904.
PRIMARY OBJECTIVES:
I. To determine whether the addition of radiotherapy to standard of care first line systemic therapy improves objective progression-free survival proportion (combined radiographic and clinical) at 18 months, compared to first line systemic therapy alone.
SECONDARY OBJECTIVES:
I. To compare objective progression free survival (PFS) (combined radiographic and clinical PFS) between arms.
II. To compare prostate specific antigen (PSA) PFS between arms.
III. To compare radiographic PFS between arms.
IV. To compare PSA response rates (>= 90% and >= 50% decline from baseline) and rate of undetectable PSA (=< 0.2 ng/mL) between arms.
V. To compare measurable disease response rate between arms.
VI. To compare non-irradiated distant metastasis free survival between arms.
VII. To compare patient-reported outcomes based on National Comprehensive Cancer Network/ Functional Assessment of Cancer Therapy (NCCN-FACT) Fire & Police Selection, Inc. (FPSI)-17 and Brief Pain Inventory (short form).
VIII. To compare overall survival between arms.
IX. To compare prostate cancer specific survival between arms.
X. To describe the adverse events associated with radiotherapy when administered in combination with first line systemic therapy.
EXPLORATORY OBJECTIVES:
I. Circulating analytes (circulating tumor deoxyribonucleic acid [DNA] [ctDNA] and circulating tumor cells [CTC]) will be evaluated alone and in combination with standard laboratory measures for biologic insights and predictive/prognostic capacities.
II. If patients were on continuous treatment with second generation androgen inhibitors (e.g. abiraterone or enzalutamide) in the metastatic hormone-sensitive phase, the ctDNA and CTC cells will be investigated before and after radiation and at 6 months post-radiotherapy to measure eradication and/or relapse of resistance signatures (AR-V7 presence, androgen receptor messenger ribonucleic acid [mRNA] copy number).
III. Gallium Ga 68-labeled PSMA-11 (68Ga-PSMA) positron emission tomography (PET)/computed tomography (CT) will be offered to patients in ARM 2 to evaluate if areas of subsequent relapse were present on the molecular study compared to standard imaging.
OUTLINE: Participants are randomized to 1 of 2 arms.
ARM I: Participants receive standard of care systemic therapy.
ARM II: Participants receive standard of care systemic therapy. Participants also undergo external beam radiotherapy within 8 weeks of randomization and complete by day 84.
After completion of study treatment, participants are followed up at 30 days, and then every 4 weeks for up to 2.5 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationUniversity of Michigan Rogel Cancer Center
Principal InvestigatorZachery Roger Reichert
- Primary IDUMCC 2017.163
- Secondary IDsNCI-2018-01650
- ClinicalTrials.gov IDNCT03556904