Dose-Escalated Salvage Radiotherapy for Prostate Cancer

(MAPS Trial)

Overseen By Pavel Noa Hechevarria

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: University of Miami

Must not be taking: Androgen deprivation

Disqualifiers: Metastatic disease, Prior pelvic radiotherapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 34 fractions (approximately 7 weeks)

37 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have had androgen deprivation therapy within the last 6 months, you cannot participate.

What data supports the effectiveness of the treatment Mapped Tumor Salvage RT (MTSRT) and Standard Salvage Radiation Treatment (SSRT) for prostate cancer?

Research shows that dose-escalated salvage radiotherapy can improve progression-free survival in patients with recurrent prostate cancer after surgery. Additionally, studies suggest that early implementation of salvage radiotherapy may enhance disease control and reduce late toxicity. ^{1 2 3 4 5}

Is dose-escalated salvage radiotherapy for prostate cancer safe?

Dose-escalated salvage radiotherapy for prostate cancer has been shown to be generally well tolerated, with no significant difference in acute side effects compared to standard doses, although some worsening in urinary quality of life was noted. Modern techniques like intensity modulated radiation therapy (IMRT) help minimize side effects, making the treatment feasible and safe for patients. ^{2 5 6 7 8}

How is the MTSRT treatment different from other prostate cancer treatments?

Mapped Tumor Salvage RT (MTSRT) is unique because it involves dose-escalated radiotherapy specifically targeted to the tumor area, potentially improving outcomes for prostate cancer patients who have had a recurrence after surgery. This approach is different from standard treatments as it aims to increase the radiation dose to the tumor while minimizing exposure to surrounding healthy tissue. ^{1 2 3 5 9}

What is the purpose of this trial?

1. The investigators hypothesize that increasing radiation dose to the functional MRI-defined lesion in the prostate bed will result in an improved initial complete response (reduction in prostate-specific antigen (PSA) to \< 0.1 ng/mL), which is related to long-term outcome biochemically. 2. Biomarker expression levels differ in the DCE-MRI enhancing and non-enhancing tumor regions (when applicable). 3. 10-15% of men undergoing RT have free circulating DNA (fcDNA) or tumor cells (CTC) that are related to an adverse treatment outcome. 4. Prostate cancer-related anxiety will be reduced in the MRI targeted SRT arm, because the patients will be aware that the dominant tumor will be targeted with higher radiation dose (compared to those pts who were treated on standard arm prior to its closure).

Research Team

Matthew Abramowitz, MD

Principal Investigator

University of Miami

Eligibility Criteria

Men aged 35-85 with prostate cancer, who've had a prostatectomy and have PSA levels between 0.1 to 4.0 ng/mL within the last three months. They should not have distant metastatic disease or previous pelvic radiotherapy, must be at least three months post-surgery, and able to sign consent.

Inclusion Criteria

I have a detectable tumor in my prostate or nearby lymph nodes, measured recently.

My cancer has not spread far, except possibly to pelvic nodes.

I don't have any other active cancers except for non-spreading skin cancer or early CLL.

Exclusion Criteria

I haven't had hormone therapy for my cancer in the last 6 months, except as part of radiation treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MRI-mapped dose-escalated salvage radiotherapy post-prostatectomy

34 fractions (approximately 7 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 65 months

Treatment Details

Interventions

• Mapped Tumor Salvage RT (MTSRT)
• Standard Salvage Radiation Treatment (SSRT)

Trial Overview The MAPS Trial is testing if increasing radiation doses directly to MRI-detected lesions in the prostate bed can improve initial response rates (lowering PSA to <0.1 ng/mL) compared to standard salvage radiation treatment.

Participant Groups

Group I: Phase 3 - Arm II: Mapped Tumor Salvage RT (MTSRT) Experimental Treatment 1 Intervention

Phase 3 Patients will receive the same treatment to the CTV of 68 Gy in 34 fractions and the Gross Tumor Volume (GTV) defined by functional imaging will receive 2.25 Gy per day for a total of 76.5 Gy (biological equivalent to 80 Gy in 2.0 Gy fractions assuming an α/β ratio of 3). this arm was continues as single arm phase 2

Group II: Phase 3 - Arm I: Standard Salvage Radiation Treatment (SSRT) Experimental Treatment 1 Intervention

Phase 3 total dose of 68 Gy will be delivered in 34 fractions to the Clinical Target Volume (CTV), 51 Gy in 34 fractions can be given to the pelvic nodes. this arm is closed

Group III: Phase 2: Mapped Tumor Salvage RT (MTSRT) Experimental Treatment 1 Intervention

Phase 2 Patients will receive the same treatment to the CTV of 68 Gy in 34 fractions and the Gross Tumor Volume (GTV) defined by functional imaging will receive 2.25 Gy per day for a total of 76.5 Gy (biological equivalent to 80 Gy in 2.0 Gy fractions assuming an α/β ratio of 3).

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Findings from Research

In a study of 554 prostate cancer patients who received salvage radiotherapy (SRT) after surgery, escalating the radiation dose to 7000 cGy or more significantly improved progression-free survival compared to lower doses, with a median follow-up of 6.8 years.

Factors such as lower tumor stages and lower Gleason scores were also associated with better progression-free survival, but the study found no significant impact on overall survival, indicating the need for longer follow-up to fully understand the benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Dose Escalation on the Efficacy of Salvage Radiotherapy for Recurrent Prostate Cancer-A Risk-Adjusted, Matched-Pair Analysis. Böhmer, D., Siegmann, A., Scharl, S., et al.[2023]

The RAVES trial is a phase III study involving 470 patients with pT3 prostate cancer, comparing early salvage radiotherapy (SRT) triggered by rising PSA levels to standard adjuvant radiotherapy (ART) given within 4 months after surgery.

As of October 2013, 258 patients have been randomized, and the trial aims to determine if observation with early SRT is as effective as ART in preventing biochemical failure, with additional assessments on patient outcomes and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase III trial to investigate the timing of radiotherapy for prostate cancer with high-risk features: background and rationale of the Radiotherapy -- Adjuvant Versus Early Salvage (RAVES) trial. Pearse, M., Fraser-Browne, C., Davis, ID., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Dose-adapted salvage radiotherapy after radical prostatectomy based on an erMRI target definition model: toxicity analysis. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Dose Escalation on the Efficacy of Salvage Radiotherapy for Recurrent Prostate Cancer-A Risk-Adjusted, Matched-Pair Analysis. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Can early implementation of salvage radiotherapy for prostate cancer improve the therapeutic ratio? A systematic review and regression meta-analysis with radiobiological modelling. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Results of Dose-adapted Salvage Radiotherapy After Radical Prostatectomy Based on an Endorectal MRI Target Definition Model. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Stereotactic radiotherapy for prostate bed recurrence after prostatectomy, a multicentric series. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Role of Dose Intensification for Salvage Radiation Therapy after Radical Prostatectomy. [2020]

7. England pubmed.ncbi.nlm.nih.gov

A Phase III trial to investigate the timing of radiotherapy for prostate cancer with high-risk features: background and rationale of the Radiotherapy -- Adjuvant Versus Early Salvage (RAVES) trial. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Comparison Between Dose-Escalated Intensity Modulated Radiation Therapy and 3-Dimensional Conformal Radiation Therapy for Salvage Radiation Therapy After Prostatectomy. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Dose-escalated salvage radiotherapy after radical prostatectomy in high risk prostate cancer patients without hormone therapy: outcome, prognostic factors and late toxicity. [2022]