Stereotactic Ablative Radiation Therapy for Abiraterone-Resistant, Oligoprogressive Metastatic Prostate Cancer

NCT ID: NCT04838899

Last Updated: 2024-04-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-16
• Study Completion Date: 2026-12-31

Brief Summary

There is increasing worldwide interest in exploring stereotactic ablative body radiotherapy (SABR) for treating metastases in men with prostate cancer, including for the treatment of oligoprogressive metastases. The latter applies to a situation whereby patients with widespread metastases undergoing systemic therapy present with a solitary or a few metastatic tumors that progress, while all other metastases are stable or responding. The usual practice would be to change systemic therapy at this point, but another approach is to locally ablate the "rogue" metastases and continue the same systemic therapy. SABR used in this scenario may delay the need to switch to another line of systemic therapy and improve progression-free survival while patients stay on the same systemic therapy.

Detailed Description

There is increasing worldwide interest in exploring the use of SABR for metastatic, treatment-naive prostate cancer, eg for delaying the need to start androgen deprivation therapy (ADT), and ultimately to improve patient outcome.

Another potential use of SABR for metastatic prostate cancer is in the setting of oligoprogression. In patients undergoing systemic therapy, oligoprogression describes the clinical situation where a solitary or a few metastatic tumors progress, while all other metastases are stable or responding. The usual practice would be to change systemic therapy at this point, but another approach is to locally ablate the "rogue" metastases and continue the same systemic therapy. There is limited clinical evidence for such an approach, eg in renal cell and non-small cell lung cancer.

While there is a lack of published evidence of such an approach in metastatic castration-resistant prostate cancer (mCPRC), SABR for oligoprogressive mCRPC in men undergoing abiraterone therapy may delay the need to switch to another line of systemic therapy, such as chemotherapy, and thereby to improve progression-free survival while patients stay on the same systemic therapy.

mCRPC is a unique solid tumor to study the oligoprogressive setting for several reasons. First, there still remains a limited number of proven systemic agents in the CRPC setting. Second, serum prostate specific antigen (PSA) is an excellent biomarker of prostate cancer activity, which is easy to collect and analyze to monitor treatment response and disease progression. Third, because of the low α/β value of prostate cancer, hypofractionated SABR may be a very effective and convenient way to eradicate areas of known disease.

The primary objective of this phase I study is to determine the incidence of acute and late toxicities associated with delivering SABR to all progressive metastatic sites in patients with metastatic CRPC who present with oligoprogression while on abiraterone. We also aim to obtain preliminary efficacy data of this novel approach. Patients will remain on abiraterone after SABR to measure the added progression-free survival.

Conditions

Oligoprogressive; Castration-Resistant Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

All metastases that fulfill the definition of oligoprogression seen on conventional imaging will be treated with standard SABR dose fractionation schemes routinely used at Sunnybrook Odette Cancer Centre. The prostate (if present and not previously treated) will be treated to a dose of 35 Gy in 5 fractions. Non-spine bone metastases will be treated to a dose of 30-40 Gy in 5 fractions. Spine metastases will be treated to a dose of 24 Gy in 2-3 fractions or 30-40 Gy in 5 fractions. Involved lymphadenopathy will be treated to a dose of 30-40 Gy in 5 fractions. Similarly, brain, lung, liver, and adrenal metastases will be treated with standard Sunnybrook SABR doses. Patients will remain on abiraterone during and after SABR treatments.

Group Type: EXPERIMENTAL

Stereotactic Body Radiation Therapy (SABR)

Intervention Type: RADIATION

SABR to oligoprogressive metastases while continuing abiraterone therapy

Interventions

Stereotactic Body Radiation Therapy (SABR)

SABR to oligoprogressive metastases while continuing abiraterone therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• ECOG performance status 0-1.
• Histologic confirmation of prostate adenocarcinoma.
• Documentation of metastatic, castration-resistant prostate cancer.
• Patient being treated with abiraterone.
• Evidence of oligoprogression (according to RECIST [V1.1] and/or Prostate Cancer Working Group criteria [PCWG3], as applicable), applying any of the following: (i) ≤ 5 metastatic lesions progressing on conventional imaging (≤ 3 progressing metastases in any one organ system) while all other metastases are controlled or responding; (ii) PSA progression only, but in the setting of oligometastases (≤ 5 metastatic lesions seen on imaging, with ≤ 3 metastases in any one organ system); in this setting, all metastases will be irradiated.
• All metastases of interest amenable to SABR.

Exclusion Criteria

• Patients presenting with unequivocal clinical progression, defined as one of the following: (i) cancer pain requiring the initiation of opioid therapy; (ii) immediate need for cytotoxic chemotherapy as per treating physician's discretion; or (iii) deterioration of performance status to grade ≥ 3 according to ECOG.
• Evidence of spinal cord compression.
• Prior malignancy within the past 5 years, excluding non-melanoma skin cancer, and in-situ cancer.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: lead

Responsible Party

Dr. Urban Emmenegger

Medical Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Odette Cancer Centre

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Urban Emmenegger, MD

Role: CONTACT

urban.emmenegger@sunnybrook.ca

+416-480-4928

Facility Contacts

Urban Emmenegger, MD

Role: primary

urban.emmenegger@sunnybrook.ca

+1-416-480-4928

Other Identifiers

#351

Identifier Type: -

Identifier Source: org_study_id