Back to resultsMRI-Mapped Dose-Escalated Salvage Radiotherapy Post-Prostatectomy: The MAPS Trial (MAPS)
Primary Purpose
Prostate Cancer, Prostate Adenocarcinoma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Standard Salvage Radiation Treatment (SSRT)
Mapped Tumor Salvage RT (MTSRT)
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer
Eligibility Criteria
Inclusion Criteria:
- Prostate cancer patients with a PSA after prostatectomy of at least 0.1 ng/mL and up to 4.0 ng/mL within 3 months prior to enrollment.
- Patients with or without palpable abnormalities on digital rectal exam (DRE) are eligible.
- Minimum of 3 months since prostatectomy to allow for return of urinary continence and healing.
- Imaging detectable lesion or lesions in prostate bed or regional lymph node (LN). Each lesion should be at least 0.4 cc and a maximum of 6 cc and was obtained ≤ 3 months prior to protocol entry or enrollment.
- No evidence of metastatic (distant) disease (pelvic nodes are allowed up to common iliac).
- Negative bone scan if deemed necessary by treating physician obtained ≤ 4 months prior to protocol entry or enrollment.
- No previous pelvic radiotherapy.
- Serum total testosterone taken within 3 months prior to enrollment.
- No concurrent, active malignancy, other than nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for ≥ 3 years then the patient is eligible.
- Ability to understand and the willingness to sign a written informed consent document.
- Zubrod performance status < 2.
- Patients must agree to fill out quality of life/psychosocial questionnaires.
- Age ≥ 35 and ≤ 85 years.
Exclusion Criteria:
a. Prior androgen deprivation therapy is not permitted if it was within 6 months previous to signing consent form. (NOTE: Therapy given as part of the planned course of radiation is allowed).
Sites / Locations
- University of MiamiRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Other
Experimental
Experimental
Arm Label
Phase 3 - Arm I: Standard Salvage Radiation Treatment (SSRT)
Phase 3 - Arm II: Mapped Tumor Salvage RT (MTSRT)
Phase 2: Mapped Tumor Salvage RT (MTSRT)
Arm Description
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
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
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).
Outcomes
Primary Outcome Measures
PSA Response Rate
PSA response rate is defined as the proportion of study patients with PSA less than 0.1 ng/mL at 21 months after completion of study treatment.
Secondary Outcome Measures
Incidence of Treatment-Emergent Toxicity
Incidence of treatment-emergent toxicity in study participants. Toxicity is defined as adverse events (AEs), serious adverse events (SAEs) and dose-limiting toxicities (DLTs)Acute toxicity is defined as toxicity occurring during treatment and within three months of completing treatment. Late toxicity is toxicity occurring more than three months after treatment completion. Toxicity will be assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Health-Related Quality of Life Scores: EPIC SF-12
Health-related Quality of Life (HRQOL) will be measured using the Expanded Prostate Cancer Index Composite and Medical Outcomes Study SF-12 (EPIC SF-12) to evaluate patient function and satisfaction after prostate cancer treatment. Response options for each item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL.
Health-Related Quality of Life Scores: MAX-PC
Health-related quality of life (HRQOL) will be measured using the scores on the Modified 18-item Memorial Anxiety Scale for Prostate Cancer (MAX-PC) from pre-treatment to post-treatment. The scale consists of 18 items (e.g. "I thought about prostate cancer even though I didn't mean to.") scored on a scale from 0 ("not at all") to 3 ("often"). Total scores range from 0 to 54, with higher scores indicating higher levels of anxiety.
Health-Related Quality of Life Scores: IPSS
Health-related quality of life (HRQOL) will be measured using the International Prostate Symptom Score (IPSS) to evaluate patient urinary function and quality of life. There are 7 questions related to urinary function. Responses are on a scale from 0 ("not at all") to 5 ("almost always"), with higher scores indicating higher levels of urinary dysfunction. There is 1 quality of life question related to urinary symptoms. Responses are on a scale from 0 ("delighted") to 6 ("terrible").
Biochemical and Clinical Failure
The cumulative incidence of biochemical or clinical failure allowing for competing risk as needed. Clinical failure is defined as at least a 25% increase in the size of the tumor relative to the smallest volume recorded, or new extension of tumor beyond the capsule, or re-extension of tumor beyond the capsule after initial regression, or urinary obstructive symptoms with carcinoma found at transurethral resection of the prostate (TURP). Biochemical failure is defined as PSA ≥ nadir + 2 ng/mL.
Failure-free Survival (FFS)
Rate of failure-free survival in study participants. Failure-free survival is defined as the elapsed time from start of radiotherapy to first documented evidence of biochemical or clinical failure or death from any cause, whichever occurs first. In the absence of any event defining failure, follow-up time will be censored at the date of last documented failure-free status.
Overall survival (OS)
Rate of overall survival in study participants. Overall survival is defined as the elapsed time from start of radiotherapy to death from any cause. For surviving patients, follow-up will be censored at the date of last contact.
Measurement of Tissue Biomarker Expression
The distribution and degree of expression of tissue biomarkers by ultrasound-directed biopsies for patients who choose to undergo the optional biopsies. Quantification of the amount of the biomarker specific immunohistochemical staining in the area of tumor.
Incidence and relationship of circulating DNA and tumor cells to tissue biomarkers
To determine the incidence and relationship of circulating DNA and tumor cells to tissue biomarkers and initial complete biochemical response.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01411345
Brief Title
MRI-Mapped Dose-Escalated Salvage Radiotherapy Post-Prostatectomy: The MAPS Trial
Acronym
MAPS
Official Title
A Phase II Randomized Trial of MRI-Mapped Dose-Escalated Salvage Radiotherapy Post-Prostatectomy: The MAPS Trial
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 12, 2012 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
June 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Miami
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Biomarker expression levels differ in the DCE-MRI enhancing and non-enhancing tumor regions (when applicable).
10-15% of men undergoing RT have free circulating DNA (fcDNA) or tumor cells (CTC) that are related to an adverse treatment outcome.
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).
Detailed Description
Phase 3 arms I (SSRT) and II (MTSRT) were closed. Study recruitment was suspended until re-opening as a single-arm Phase 2 (MTSRT) study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Prostate Adenocarcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Phase 3 - Arm I: Standard Salvage Radiation Treatment (SSRT)
Arm Type
Other
Arm Description
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
Arm Title
Phase 3 - Arm II: Mapped Tumor Salvage RT (MTSRT)
Arm Type
Experimental
Arm Description
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
Arm Title
Phase 2: Mapped Tumor Salvage RT (MTSRT)
Arm Type
Experimental
Arm Description
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).
Intervention Type
Radiation
Intervention Name(s)
Standard Salvage Radiation Treatment (SSRT)
Other Intervention Name(s)
SSRT
Intervention Description
A total dose of 68 Gy delivered in 34 fractions to the Clinical Target Volume (CTV), 51 Gy in 34 fractions can be given to the pelvic nodes.
Intervention Type
Radiation
Intervention Name(s)
Mapped Tumor Salvage RT (MTSRT)
Intervention Description
Dose escalation to the imaging or Dynamic Contrast Enhanced MRI (DCE-MRI)-defined dominant region(s) by dose painting at 2.25 Gy per fraction, while the rest of the Clinical Target Volume (CTV) receives 2.0 Gy a fraction to 68 Gy. The mapped tumor (MT) boost region will receive an absolute dose of 76.5 Gy. Assuming an α/β ratio of 3.0, this would be equivalent to 80 Gy in 2.0 Gy fractions.
Primary Outcome Measure Information:
Title
PSA Response Rate
Description
PSA response rate is defined as the proportion of study patients with PSA less than 0.1 ng/mL at 21 months after completion of study treatment.
Time Frame
21 months Post-Completion of Protocol Therapy
Secondary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Toxicity
Description
Incidence of treatment-emergent toxicity in study participants. Toxicity is defined as adverse events (AEs), serious adverse events (SAEs) and dose-limiting toxicities (DLTs)Acute toxicity is defined as toxicity occurring during treatment and within three months of completing treatment. Late toxicity is toxicity occurring more than three months after treatment completion. Toxicity will be assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame
Up to 3 months post-completion of therapy
Title
Health-Related Quality of Life Scores: EPIC SF-12
Description
Health-related Quality of Life (HRQOL) will be measured using the Expanded Prostate Cancer Index Composite and Medical Outcomes Study SF-12 (EPIC SF-12) to evaluate patient function and satisfaction after prostate cancer treatment. Response options for each item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL.
Time Frame
Up to 5.25 years post-Protocol Therapy
Title
Health-Related Quality of Life Scores: MAX-PC
Description
Health-related quality of life (HRQOL) will be measured using the scores on the Modified 18-item Memorial Anxiety Scale for Prostate Cancer (MAX-PC) from pre-treatment to post-treatment. The scale consists of 18 items (e.g. "I thought about prostate cancer even though I didn't mean to.") scored on a scale from 0 ("not at all") to 3 ("often"). Total scores range from 0 to 54, with higher scores indicating higher levels of anxiety.
Time Frame
Up to 5.25 years post-Protocol Therapy
Title
Health-Related Quality of Life Scores: IPSS
Description
Health-related quality of life (HRQOL) will be measured using the International Prostate Symptom Score (IPSS) to evaluate patient urinary function and quality of life. There are 7 questions related to urinary function. Responses are on a scale from 0 ("not at all") to 5 ("almost always"), with higher scores indicating higher levels of urinary dysfunction. There is 1 quality of life question related to urinary symptoms. Responses are on a scale from 0 ("delighted") to 6 ("terrible").
Time Frame
Up to 5.25 years post-Protocol Therapy
Title
Biochemical and Clinical Failure
Description
The cumulative incidence of biochemical or clinical failure allowing for competing risk as needed. Clinical failure is defined as at least a 25% increase in the size of the tumor relative to the smallest volume recorded, or new extension of tumor beyond the capsule, or re-extension of tumor beyond the capsule after initial regression, or urinary obstructive symptoms with carcinoma found at transurethral resection of the prostate (TURP). Biochemical failure is defined as PSA ≥ nadir + 2 ng/mL.
Time Frame
Up to 5.25 years post-Protocol Therapy
Title
Failure-free Survival (FFS)
Description
Rate of failure-free survival in study participants. Failure-free survival is defined as the elapsed time from start of radiotherapy to first documented evidence of biochemical or clinical failure or death from any cause, whichever occurs first. In the absence of any event defining failure, follow-up time will be censored at the date of last documented failure-free status.
Time Frame
Up to 5.25 years post-Protocol Therapy
Title
Overall survival (OS)
Description
Rate of overall survival in study participants. Overall survival is defined as the elapsed time from start of radiotherapy to death from any cause. For surviving patients, follow-up will be censored at the date of last contact.
Time Frame
Up to 5.25 years post-Protocol Therapy
Title
Measurement of Tissue Biomarker Expression
Description
The distribution and degree of expression of tissue biomarkers by ultrasound-directed biopsies for patients who choose to undergo the optional biopsies. Quantification of the amount of the biomarker specific immunohistochemical staining in the area of tumor.
Time Frame
Up to 5.25 years post-Protocol Therapy
Title
Incidence and relationship of circulating DNA and tumor cells to tissue biomarkers
Description
To determine the incidence and relationship of circulating DNA and tumor cells to tissue biomarkers and initial complete biochemical response.
Time Frame
Up to 5.25 years post-Protocol Therapy
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Prostate cancer patients with a PSA after prostatectomy of at least 0.1 ng/mL and up to 4.0 ng/mL within 3 months prior to enrollment.
Patients with or without palpable abnormalities on digital rectal exam (DRE) are eligible.
Minimum of 3 months since prostatectomy to allow for return of urinary continence and healing.
Imaging detectable lesion or lesions in prostate bed or regional lymph node (LN). Each lesion should be at least 0.4 cc and a maximum of 6 cc and was obtained ≤ 3 months prior to protocol entry or enrollment.
No evidence of metastatic (distant) disease (pelvic nodes are allowed up to common iliac).
Negative bone scan if deemed necessary by treating physician obtained ≤ 4 months prior to protocol entry or enrollment.
No previous pelvic radiotherapy.
Serum total testosterone taken within 3 months prior to enrollment.
No concurrent, active malignancy, other than nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for ≥ 3 years then the patient is eligible.
Ability to understand and the willingness to sign a written informed consent document.
Zubrod performance status < 2.
Patients must agree to fill out quality of life/psychosocial questionnaires.
Age ≥ 35 and ≤ 85 years.
Exclusion Criteria:
a. Prior androgen deprivation therapy is not permitted if it was within 6 months previous to signing consent form. (NOTE: Therapy given as part of the planned course of radiation is allowed).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pavel Noa Hechevarria
Phone
305-243-1036
Email
pavel.noa@med.miami.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew C Abramowitz, MD
Organizational Affiliation
University of Miami
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pavel N Hechevarria
Phone
305-243-1036
Email
pavel.noa@med.miami.edu
First Name & Middle Initial & Last Name & Degree
Alan Pollack, MD, PhD
First Name & Middle Initial & Last Name & Degree
Matthew Abramowitz, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
MRI-Mapped Dose-Escalated Salvage Radiotherapy Post-Prostatectomy: The MAPS Trial
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