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RAdium-223 and SABR Versus SABR for Oligometastatic Prostate Cancers (RAVENS)

Primary Purpose

Prostate Cancer

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Radium-223

stereotactic ablative radiotherapy (SABR)

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Patient must have at least one and up to three asymptomatic metastatic tumor(s) of the bone or soft tissue (with at least one bone metastasis) develop within the past 6-months that are ≤ 5.0 cm or <250 cm3
Patient must have had their primary tumor treated with surgery and/or radiation.
Histologic confirmation of malignancy (primary or metastatic tumor).
PSADT <15 months. PSA doubling time (PSADT) will be calculated using as many PSA values that are available from time of relapse (PSA > 0.2). To calculate PSADT, the Memorial Sloan Kettering Cancer Center Prostate Cancer Prediction Tool will be used. It can be found at the following web site: https://www.mskcc.org/nomograms/prostate/psa-doubling-time.
Patient may have had prior systemic therapy and/or ADT associated with treatment of their primary prostate cancer. Patient may have had ADT associated with salvage radiation therapy (to the primary prostate cancer or pelvis is allowed).
PSA > 0.5 but <50.
Testosterone > 125 ng/dL.
Patient must be ≥ 18 years of age.
Patient must have a life expectancy ≥ 12 months.
Patient must have an ECOG performance status ≤ 2.
Patient must have normal organ and marrow function as defined as:

Before the first administration of Xofigo, the absolute neutrophil count (ANC) should be ≥ 1.5 x 109/L, the platelet count ≥ 100 x 109/L and hemoglobin ≥ 10 g/dL.

* Patient must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

No more than 3 years of ADT is allowed, with the most recent ADT treatment having occurred greater than 6 months prior to enrollment.
PSMA-PET/MRI or PSMA-PET/CT scan within the past 6 months with results that demonstrate more disease lesions than baseline CT/Bone Scan
Castration-resistant prostate cancer (CRPC).
Spinal cord compression or impending spinal cord compression.
Suspected pulmonary and/or liver metastases (greater >10 mm in largest axis).
Patient receiving any other investigational agents.
Patient receiving abiraterone and prednisone.
Patient is participating in a concurrent treatment protocol.
Serum creatinine > 3 times the upper limit of normal.
Total bilirubin > 3 times the upper limit of normal.
Liver Transaminases > 5-times the upper limit of normal.
Unable to lie flat during or tolerate PET/MRI, PET/CT or SBRT.
Prior salvage treatment to the primary prostate cancer or pelvis is allowed.
Refusal to sign informed consent.

Sites / Locations

Johns Hopkins

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Radium-223 and SABR

SABR

Arm Description

First radium-223 infusion will be within two weeks of SABR

SABR(1-5 fractions) will be administered for all men

Outcomes

Primary Outcome Measures

Progression-free survival

Time to progression in men who have oligometastatic prostate cancer after therapy. Progression is defined by PCWG2 criteria as follows: >=25% increase in PSA from nadir (and by >=2ng/mL), and/or clinical/radiographic progression (clinical progression = symptomatic progression, worsening of disease-related symptoms or new cancer-related complications; radiographic progression on CT scan defined by RECIST 1.1 criteria: >=20% enlargement in sum diameter of soft-tissue target lesions; or on bone scan >=1 new bone lesions), initiation of ADT or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Toxicity as assessed by number of participants who experience adverse events

Number of participants who receive at least one fraction of SABR and Radium-223 who experience adverse events as defined by CTCAE v4.0 after first treatment of SABR and Radium-223.

Local control at 12 months

Time from starting treatment until local relapse is documented

Time to locoregional progression

Time from starting treatment until local and/or regional relapse is documented

Time to distant progression

Time from starting treatment until distant relapse is documented

Time to new metastasis

time from starting treatment to the time of a new documented tumor metastasis by CT and/or bone scan. Subjects who do not progress will be censored at the time of the last contact.

ADT-free survival

Time from randomization until initiation of androgen-deprivation therapy (ADT).

Quality of Life as assessed by Pain Severity and Pain Interference using the Brief Pain Inventory

The brief pain inventory assesses the severity of pain, location of pain, amount of pain over the last 24 hours, and impact of pain on daily functions. Scores for the 4 pain severity items and 7 pain interference items range from 0-10, where 10 is the worst pain or pain that completely interferes with described activity and 0 is the least pain or does not interfere with described activity. The mean of these scores is used to measure pain severity and pain interference.

Full Information

NCT ID

NCT04037358

First Posted

July 26, 2019

Last Updated

May 30, 2023

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

1. Study Identification

Unique Protocol Identification Number

NCT04037358

Brief Title

RAdium-223 and SABR Versus SABR for Oligometastatic Prostate Cancers

Acronym

RAVENS

Official Title

A Phase II Randomized Trial of RAdium-223 and SABR Versus SABR for oligomEtastatic Prostate caNcerS (RAVENS)

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 9, 2019 (Actual)

Primary Completion Date

December 2026 (Anticipated)

Study Completion Date

December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

This is a Phase II non-blinded randomized study evaluating men with oligometastatic prostate cancer lesions randomized (1:1) to stereotactic ablative radiation therapy (SABR) versus SBAR + Radium-223. We are looking to determine the progression-free survival of men who have oligometastatic prostate cancer with at least one bone metastasis with stereotactic ablative radiation therapy (SABR) versus SABR + Radium-223.

Detailed Description

The metastatic capacity of prostate cancer (PCa) behaves along a spectrum of disease that contains an oligometastatic state where metastases are limited in number and location. The importance of local consolidation of all tumor deposits in oligometastatic disease to forestall further metastatic dissemination is now backed by small randomized studies. Our previous Baltimore ORIOLE randomized trial of stereotactic ablative radiation (SABR) alone, highly focused, high-dose radiation, versus observation in oligometastatic PCa final data demonstrate a progression-free survival (PFS) benefit of SABR alone. The patterns of failure from our ORIOLE trial in combination with prior data suggest one dominant mode of failure is from microscopic disease particularly those with bone-tropic biology. These are important early clinical data suggesting the existence of an oligometastatic state and the importance of local therapies in the management of these patients. Radiopharmaceutical therapy (RPT) approaches have not been applied in the oligometastatic space and thus the opportunity to target micrometastatic disease in conjunction with local consolidation of macroscopic disease with SABR has the potential to provide a curative paradigm for patients with oligometastatic PCa. We introduce the successor trial to ORIOLE called RAVENS that is a phase II randomized trial of SABR +/- the bone metastasis seeking RPT Xofigo in men with oligometastatic PCa. We hypothesize macroscopic prostate tumors support the growth of and help nurture future distant metastases and this process can be impacted most by total, macro- and microscopic, tumor consolidation. In addition, we hypothesize that circulating biomarkers can identify men with oligometastasis that benefit the most from SABR and RPT.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

RAdium-223 and SABR Versus SABR (Stereotactic Ablative Radiotherapy)

Masking

None (Open Label)

Allocation

Randomized

Enrollment

64 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Radium-223 and SABR

Arm Type

Experimental

Arm Description

First radium-223 infusion will be within two weeks of SABR

Arm Title

SABR

Arm Type

Active Comparator

Arm Description

SABR(1-5 fractions) will be administered for all men

Intervention Type

Drug

Intervention Name(s)

Radium-223

Intervention Description

Radium-223 plus SABR will be within two weeks.

Intervention Type

Radiation

Intervention Name(s)

stereotactic ablative radiotherapy (SABR)

Intervention Description

SABR 1-5 fractions

Primary Outcome Measure Information:

Title

Progression-free survival

Description

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Toxicity as assessed by number of participants who experience adverse events

Description

Number of participants who receive at least one fraction of SABR and Radium-223 who experience adverse events as defined by CTCAE v4.0 after first treatment of SABR and Radium-223.

Time Frame

12 months

Title

Local control at 12 months

Description

Time from starting treatment until local relapse is documented

Time Frame

12 months

Title

Time to locoregional progression

Description

Time from starting treatment until local and/or regional relapse is documented

Time Frame

12 months

Title

Time to distant progression

Description

Time from starting treatment until distant relapse is documented

Time Frame

12 months

Title

Time to new metastasis

Description

time from starting treatment to the time of a new documented tumor metastasis by CT and/or bone scan. Subjects who do not progress will be censored at the time of the last contact.

Time Frame

12 months

Title

ADT-free survival

Description

Time from randomization until initiation of androgen-deprivation therapy (ADT).

Time Frame

12 months

Title

Quality of Life as assessed by Pain Severity and Pain Interference using the Brief Pain Inventory

Description

Time Frame

12 months

10. Eligibility

Sex

Male

Gender Based

Yes

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

100 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patient must have at least one and up to three asymptomatic metastatic tumor(s) of the bone or soft tissue (with at least one bone metastasis) develop within the past 6-months that are ≤ 5.0 cm or <250 cm3 Patient must have had their primary tumor treated with surgery and/or radiation. Histologic confirmation of malignancy (primary or metastatic tumor). PSADT <15 months. PSA doubling time (PSADT) will be calculated using as many PSA values that are available from time of relapse (PSA > 0.2). To calculate PSADT, the Memorial Sloan Kettering Cancer Center Prostate Cancer Prediction Tool will be used. It can be found at the following web site: https://www.mskcc.org/nomograms/prostate/psa-doubling-time. Patient may have had prior systemic therapy and/or ADT associated with treatment of their primary prostate cancer. Patient may have had ADT associated with salvage radiation therapy (to the primary prostate cancer or pelvis is allowed). PSA > 0.5 but <50. Testosterone > 125 ng/dL. Patient must be ≥ 18 years of age. Patient must have a life expectancy ≥ 12 months. Patient must have an ECOG performance status ≤ 2. Patient must have normal organ and marrow function as defined as: Before the first administration of Xofigo, the absolute neutrophil count (ANC) should be ≥ 1.5 x 109/L, the platelet count ≥ 100 x 109/L and hemoglobin ≥ 10 g/dL. * Patient must have the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: No more than 3 years of ADT is allowed, with the most recent ADT treatment having occurred greater than 6 months prior to enrollment. PSMA-PET/MRI or PSMA-PET/CT scan within the past 6 months with results that demonstrate more disease lesions than baseline CT/Bone Scan Castration-resistant prostate cancer (CRPC). Spinal cord compression or impending spinal cord compression. Suspected pulmonary and/or liver metastases (greater >10 mm in largest axis). Patient receiving any other investigational agents. Patient receiving abiraterone and prednisone. Patient is participating in a concurrent treatment protocol. Serum creatinine > 3 times the upper limit of normal. Total bilirubin > 3 times the upper limit of normal. Liver Transaminases > 5-times the upper limit of normal. Unable to lie flat during or tolerate PET/MRI, PET/CT or SBRT. Prior salvage treatment to the primary prostate cancer or pelvis is allowed. Refusal to sign informed consent.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Phuoc Tran, M.D., Ph.D.

Organizational Affiliation

Johns Hopkins SKCCC

Official's Role

Principal Investigator

Facility Information:

Facility Name

Johns Hopkins

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32487038

Citation

Hasan H, Deek MP, Phillips R, Hobbs RF, Malek R, Radwan N, Kiess AP, Dipasquale S, Huang J, Caldwell T, Leitzel J, Wendler D, Wang H, Thompson E, Powell J, Dudley S, Deville C, Greco SC, Song DY, DeWeese TL, Gorin MA, Rowe SP, Denmeade S, Markowski M, Antonarakis ES, Carducci MA, Eisenberger MA, Pomper MG, Pienta KJ, Paller CJ, Tran PT. A phase II randomized trial of RAdium-223 dichloride and SABR Versus SABR for oligomEtastatic prostate caNcerS (RAVENS). BMC Cancer. 2020 Jun 1;20(1):492. doi: 10.1186/s12885-020-07000-2.

Results Reference

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RAdium-223 and SABR Versus SABR for Oligometastatic Prostate Cancers

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