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
• Interventions: Radiation: Hypofractionated Radiation Therapy; Procedure: Metastasectomy; Other: Quality-of-Life Assessment; Radiation: Intensity-Modulated Radiation Therapy; Other: Questionnaire Administration; Radiation: Stereotactic Body Radiation Therapy

• 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.

Study Timeline

• Study First Submitted: 2019-01-04
• Study First Submitted QC: 2019-01-04
• Study First Posted: 2019-01-08
• Study Start: 2019-09-09
• Primary Completion: 2023-12-12
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-29
• Last Update Posted: 2024-03-01
• Study Completion: 2026-06-30

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (radiation therapy)	Hypofractionated Radiation Therapy	Patients with bone metastases undergo SBR) or hypofractionated radiation per institutional standard of care guidelines at investigator's discretion.
Arm A (radiation therapy)	Quality-of-Life Assessment	Patients with bone metastases undergo SBR) or hypofractionated radiation per institutional standard of care guidelines at investigator's discretion.
Arm A (radiation therapy)	Questionnaire Administration	Patients with bone metastases undergo SBR) or hypofractionated radiation per institutional standard of care guidelines at investigator's discretion.
Arm B (salvage oligometastasectomy)	Questionnaire Administration	Patients with nodal metastases undergo salvage oligometastasectomy.
Arm B (salvage oligometastasectomy)	Quality-of-Life Assessment	Patients with nodal metastases undergo salvage oligometastasectomy.
Arm A (radiation therapy)	Stereotactic Body Radiation Therapy	Patients with bone metastases undergo SBR) or hypofractionated radiation per institutional standard of care guidelines at investigator's discretion.
Arm B (salvage oligometastasectomy)	Metastasectomy	Patients with nodal metastases undergo salvage oligometastasectomy.
Arm C (salvage oligometastasectomy, radiation therapy)	Intensity-Modulated Radiation Therapy	Patients with nodal metastases undergo salvage oligometastasectomy. Following recovery, patients undergo SBRT or hypofractionated radiation per institutional standard of care guidelines at investigator's discretion. Within 4 months following completion of salvage therapy (defined as the combination of oligometastasectomy and/or bone radiation) and depending on PSA response as well as previous treatment, patients may receive adjuvant nodal IMRT.
Arm C (salvage oligometastasectomy, radiation therapy)	Hypofractionated Radiation Therapy	Patients with nodal metastases undergo salvage oligometastasectomy. Following recovery, patients undergo SBRT or hypofractionated radiation per institutional standard of care guidelines at investigator's discretion. Within 4 months following completion of salvage therapy (defined as the combination of oligometastasectomy and/or bone radiation) and depending on PSA response as well as previous treatment, patients may receive adjuvant nodal IMRT.
Arm C (salvage oligometastasectomy, radiation therapy)	Metastasectomy	Patients with nodal metastases undergo salvage oligometastasectomy. Following recovery, patients undergo SBRT or hypofractionated radiation per institutional standard of care guidelines at investigator's discretion. Within 4 months following completion of salvage therapy (defined as the combination of oligometastasectomy and/or bone radiation) and depending on PSA response as well as previous treatment, patients may receive adjuvant nodal IMRT.
Arm C (salvage oligometastasectomy, radiation therapy)	Quality-of-Life Assessment	Patients with nodal metastases undergo salvage oligometastasectomy. Following recovery, patients undergo SBRT or hypofractionated radiation per institutional standard of care guidelines at investigator's discretion. Within 4 months following completion of salvage therapy (defined as the combination of oligometastasectomy and/or bone radiation) and depending on PSA response as well as previous treatment, patients may receive adjuvant nodal IMRT.
Arm C (salvage oligometastasectomy, radiation therapy)	Stereotactic Body Radiation Therapy	Patients with nodal metastases undergo salvage oligometastasectomy. Following recovery, patients undergo SBRT or hypofractionated radiation per institutional standard of care guidelines at investigator's discretion. Within 4 months following completion of salvage therapy (defined as the combination of oligometastasectomy and/or bone radiation) and depending on PSA response as well as previous treatment, patients may receive adjuvant nodal IMRT.
Arm C (salvage oligometastasectomy, radiation therapy)	Questionnaire Administration	Patients with nodal metastases undergo salvage oligometastasectomy. Following recovery, patients undergo SBRT or hypofractionated radiation per institutional standard of care guidelines at investigator's discretion. Within 4 months following completion of salvage therapy (defined as the combination of oligometastasectomy and/or bone radiation) and depending on PSA response as well as previous treatment, patients may receive adjuvant nodal IMRT.

Primary Outcome Measures

Name	Time	Method
Prostate-specific antigen (PSA) response rate	At 6 months after completion of treatment	Defined according to Prostate Cancer Working Group (PCWG3) criteria as the proportion of patients achieving a PSA decline \>= 50% at 6 months after completion of treatment (salvage + - adjuvant). All study data will use descriptive statistics and will be exploratory only.

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse events	Up to 3 years	Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All study data will use descriptive statistics and will be exploratory only.
PSA progression-free survival (PFS)	Time elapsed between completion of treatment (salvage + - adjuvant) and the first occurrence of confirmed PSA progression, assessed up to 3 years	Assessed according to PCWG3 criteria. All study data will use descriptive statistics and will be exploratory only.
Time to disease recurrence	Time elapsed between study enrollment and first occurrence of confirmed radiographic disease progression, assessed up to 3 years	Time from study enrollment until the date of confirmed radiographic disease progression as defined by RECIST 1.1 and PCWG3.
Time to antiandrogen therapy (ADT)	Time elapsed between study enrollment and initiation of ADT up to 3 years	All study data will use descriptive statistics and will be exploratory only.
Rate of undetectable PSA	Up to 3 years	Patients previously treated with prostatectomy evaluate the proportion of patients whose PSA remains =\< 0.2 ng/mL after 6 and 12 months following completion of treatment (salvage + - adjuvant). All study data will use descriptive statistics and will be exploratory only.
Assess impact of study treatment on Change in quality of life over 3 years	Up to 3 years	Quality of Life (QOL) questionnaires (FACT-P and Expanded Prostate Cancer Index Composite EPIC-26) administered at screening, response assessment visit, and each follow up visit.

Trial Locations

Locations (1)

Huntsman Cancer Institute/University of Utah; 🇺🇸 Salt Lake City, Utah, United States