Salvage Oligometastasectomy and Radiation Therapy in Recurrent Prostate Cancer

Phase 2

Active, not recruiting

Conditions: Recurrent Prostate Carcinoma
Metastatic Malignant Neoplasm in the Bone
Prostate Adenocarcinoma
PSA Failure
Oligometastasis
Metastatic Malignant Neoplasm in the Lymph Nodes

Registration Number: NCT03796767

Lead Sponsor: University of Utah

Brief Summary: This phase II trial studies how well surgery and radiation therapy work in treating patients with prostate cancer that has come back or spread to other parts of the body. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Surgical procedures, such as oligometastasectomy, may remove tumor cells that have spread to other parts of the body. Surgery and radiation therapy may work better in treating patients with prostate cancer that has come back or spread to other parts of the body.

Detailed Description: PRIMARY OBJECTIVES:

I. To assess response to treatment of oligometastatic disease.

SECONDARY OBJECTIVES:

I. To assess additional measurements of response to treatment of oligometastatic disease.

II. To assess prostate-specific antigen (PSA) progression free-survival following treatment of oligometastatic disease.

III. To assess time to disease recurrence following treatment of oligometastatic disease.

IV. To assess time to initiation of antiandrogen therapy (ADT) for metastatic prostate cancer following treatment of oligometastatic disease.

V. To assess the rate of undetectable PSA following treatment of oligometastatic disease in subjects who have previously undergone prostatectomy.

VI. To assess safety. VII. To assess the impact of study treatment on change in quality of life over three years.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: Male

Target Recruitment: 20

Inclusion Criteria

Histologically proven adenocarcinoma of the prostate.
Recurrent prostate carcinoma after definitive therapy for primary disease defined as:
- Post-prostatectomy (with/without adjuvant radiotherapy): Patients must have a detectable or rising PSA level that is > 0.05 ng/mL, with a second confirmatory level of > 0.05 ng/mL after a minimum of 1 week.
- Post radiotherapy/ablation (without radical prostatectomy): PSA rise >= 2ng/mL over nadir.
Subjects treated with prior definitive radiotherapy for prostate cancer who have positive molecular imaging (e.g., fluciclovine PET/CT scan or other per PI discretion) suggesting recurrent intraprostatic disease must undergo transrectal ultrasound (TRUS) biopsy less than or equal to one year before study enrollment:
- If the TRUS biopsy is negative, no additional treatment is required to the prostate in addition to that of scan positive sites.
- If the TRUS biopsy is positive, subject must undergo salvage prostatectomy or salvage radiotherapy to the primary site concurrently with the study treatment per the treatment protocol algorithm.
- NOTE: Biopsy is not required for prostate fossa recurrences after radical prostatectomy.
Oligometastatic disease defined as 10 or fewer metastatic lesions to lymph nodes and/or bones only.
For patients with oligometastatic disease involving lymph nodes, metastasis is confined to the pelvic or para-aortic (below IMA) regions on molecular imaging (e.g., fluciclovine PET/CT or PSMA PET/CT scan or other per PI discretion).
All subjects must be surgical candidates if surgery is indicated per the treatment algorithm.
Eastern Cooperative Oncology Group (ECOG) performance status =< 2.
Use of condoms for male subjects who have not had surgical removal of their prostate and have a partner of child bearing potential beginning at the time of informed consent form (ICF) signature and lasting until at least 6 months after the last radiation treatment. Because of the potential side effect on spermatogenesis associated with radiation, female partners of childbearing potential must agree to use a highly effective contraceptive method during and for 6 months after completing treatment.
Recovery to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v)5 from toxicities related to any prior treatments, unless adverse event (AE)(s) are clinically non-significant and/or stable on supportive therapy as determined by the treating physician.
Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria

Known brain or visceral metastases other than lymph nodes as defined by CT, MRI, or othermolecular imaging (e.g., fluciclovine PET/CT or PSMA PET/CT scan or other per PI discretion).
Patients actively receiving hormone therapy for prostate cancer. Patients may have received hormone therapy perviously but must have documented non-castrate levels of testosterone (>50 ng/dL)
Prior or concurrent malignancy whose natural history or treatment, in the opinion of the enrolling investigator, may have the potential to interfere wih the safety or efficay assessment of the investigational treatment protocol of the study.
Use of finasteride within 30 days prior to initiation of therapy. Baseline PSA should not be obtained prior to 30 days after stopping finasteride.
Use of dutasteride within 90 days prior to initiation of therapy. Baseline PSA should not be obtained prior to 90 days after stopping dutasteride.
Use of any prohibited therapy.
Active, uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
- Cardiovascular disorders:
  - Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
  - Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mmHg systolic or > 100 mmHg diastolic despite optimal antihypertensive treatment.
  - Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose.
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration or within 30 days of registration.
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Prostate-specific Antigen (PSA) ≥ 50% 6 Months After Completion of All Treatment	6 months after completion of 5-21 weeks of treatment	The primary outcome measure will report the count of patients achieving a PSA decline \>= 50% at 6 months after completion of treatment (salvage + - adjuvant). Prostate-Specific Antigen (PSA) is a protein produced by tissue in the prostate. An elevated PSA value can be a sign of prostate cancer.

Secondary Outcome Measures

Name	Time	Method
Prostate-specific Antigen (PSA) ≥ 50% 12 Months After Completion of All Treatment	12 months after completion of 5-21 weeks of treatment	Defined according to Prostate Cancer Working Group (PCWG3) criteria as the proportion of patients achieving a PSA decline \>= 50% at 12 months after completion of treatment (salvage + - adjuvant). Prostate-Specific Antigen (PSA) is a protein produced by tissue in the prostate. An elevated PSA value can be a sign of prostate cancer.
Prostate-specific Antigen (PSA) ≥ 90%	6 and 12 months after completion of 5-21 weeks of treatment 6 Months After Completion of All Treatment6 Months After Completion of All Treatment	This outcome will report the count of patients achieving a PSA decline ≥ 90% 6 at 6 and12 months after completion of treatment (salvage + - adjuvant). Prostate-Specific Antigen (PSA) is a protein produced by tissue in the prostate. An elevated PSA value can be a sign of prostate cancer.
PSA Progression Free-survival	Time elapsed between study enrollment and first occurrence of confirmed radiographic disease progression, assessed up to 3 years	The proportion of subjects without PSA progression (defined using Prostate Cancer Working Group 3 Criteria PCWG3), evaluated every 3 months for 3 years after completion of all treatment (salvage and adjuvant therapy).
To Assess Time to Disease Recurrence Following Treatment of Oligometastatic Disease.	Time elapsed between study enrollment and confirmed radiographic disease progression, up to 3 years	The time from study enrollment until the date of confirmed radiographic disease progression as defined by RECIST 1.1 and PCWG3.
To Assess Time to Initiation of ADT for Metastatic Prostate Cancer Following Treatment of Oligometastatic Disease.	Up to 3 years	The time from study enrollment to the initiation of ADT
Undetectable PSA	6 and 12 months after completion of 5-21 weeks of treatment	This outcome measure will report the count of participants with undetectable PSA after 6 and 12 months following completion of treatment (salvage ± adjuvant). Undetectable PSA is defined as the number of patients ever treated with prostatectomy whose PSA remains ≤ 0.2 ng/mL.
Number of Participants With Adverse Events (AE) by Grade	Up to 12 months after completion of 5-21 weeks of treatment	This outcome measure will assess the safety and tolerability of the study treatment. The severity of AEs was assessed using CTCAE v5.0 criteria, a 1-5 scale with higher numbers indicating greater severity. Grade 1 indicates "mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated" and Grade 5 indicates "death related to AE". This outcome measure will report the count of participants who experienced each AE grade. Subjects were monitored for adverse events from the start of treatment until 28 days after the last dose of the study drug. Adverse events were collected every three months for one year after treatment discontinuation.
Quality of Life (QOL) - The Functional Assessment of Cancer Therapy - Prostate (FACT-P)	up to 45 days after the initiation of study therapy	FACT-P is a QOL questionnaires administered at the Response Assessment Visit. FACT-P is used to assess the health-related QOL in prostate cancer. Patients indicate which symptoms/problems they've experienced during the past week, from 1 Not at All to 4 Very Much. The assessment was scored according to the "FACT-P Scoring Guidelines (Version 4)". Individual items that were "reverse items" (high value indicates poor QOL) were subtracted from 4; reverse and normal items were added to calculate each subscale. The higher the subscale the better the QOL. The subscales and score ranges are: Physical Well-Being (0-28), Social/ Family Well Being (0-28), Emotional Well-Being (0-24), Functional Well Being (0-28), and Prostate Cancer Subscale (0-48) This outcome will report the mean score and 95% confidence interval of each subscale.
Quality of Life (QOL): Expanded Prostate Cancer Index Composite (EPIC-26)	up to 45 days after initiation of study therapy	EPIC-26 is a Health Related Quality of Life (HRQOL) questionnaires assessing the disease-specific aspects of prostate cancer and its therapies. This questionnaire asks patients to rank symptoms from 1 More than once a day to 5 Rarely or never. EPOC-26 reports 5 subscales: Urinary Incontinence Score, Urinary Obstructive/ Irritative Score, Bowel Score, Sexual Score, and Urinary Incontinence Score. Multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL.

Trial Locations

Locations (1): Huntsman Cancer Institute/University of Utah
🇺🇸
Salt Lake City, Utah, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States