A Phase III Randomized Trial of MRI-Mapped Dose-Escalated Salvage Radiotherapy Post-Prostatectomy: The MAPS Trial - Full Text View

Purpose

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 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.
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.

Condition	Intervention	Phase
Prostate Cancer Prostate Adenocarcinoma	Radiation: Standard Salvage Radiation Treatment (SSRT) Radiation: Mapped Tumor Salvage RT (MTSRT) Procedure: DCE-MRI of Pelvis/Prostate Procedure: Bone Scan Procedure: Ultrasound Prostate Bed Biopsy Procedure: Urine Sample Collection Procedure: Blood Sample Collection Behavioral: EPIC SF-12 Questionnaire Behavioral: MAC-PC Questionnaire	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase III Randomized Trial of MRI-Mapped Dose-Escalated Salvage Radiotherapy Post-Prostatectomy: The MAPS Trial

Resource links provided by NLM:

MedlinePlus related topics: Anxiety Cancer Nuclear Scans Prostate Cancer Urine and Urination

U.S. FDA Resources

Further study details as provided by University of Miami Sylvester Comprehensive Cancer Center:

Primary Outcome Measures:

Effect of Radiation boost to the MRI Lesion [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
The primary objective is to determine the effect of radiation boost to the MRI lesion on initial complete biochemical response.

Secondary Outcome Measures:

Impact of SRT boost to MRI-identified lesion on toxicity and quality of life [ Time Frame: 5.25 years ] [ Designated as safety issue: Yes ]
To determine the impact of SRT boost to the MRI-identified lesion on toxicity, health-related quality of life (HRQOL), prostate cancer-specific anxiety, and prostate cancer-specific QOL.
Biochemical and clinical failure; failure-free survival, overall survival [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
To evaluate biochemical and clinical failure, failure-free survival, and overall survival.
Biomarker expression [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
To determine the distribution and degree of expression of tissue biomarkers by US-directed biopsies.
Incidence and relationship of circular DNA and tumor cells to tissue biomarkers [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
To determine the incidence and relationship of circulating DNA and tumor cells to tissue biomarkers and initial complete biochemical response.

Estimated Enrollment:	80
Study Start Date:	June 2011
Estimated Study Completion Date:	June 2017
Estimated Primary Completion Date:	June 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm I: SSRT Standard Salvage Radiation Treatment (SSRT)	Radiation: Standard Salvage Radiation Treatment (SSRT) Patients will receive 68 Gy in 2 Gy fractions to the prostate bed clinical target volume (CTV). Procedure: DCE-MRI of Pelvis/Prostate Dynamic Contrast Enhanced-MRI of the Pelvis/Prostate prior to radiation therapy, 3 months, 9 months and 2 years post-radiation therapy Procedure: Bone Scan Bone scan prior to radiation therapy for a PSA of >= 2 or physician concern for metastasis. Procedure: Ultrasound Prostate Bed Biopsy Ultrasound Prostate Bed Biopsy prior to radiation therapy; 2 - 2.5 years post radiation therapy. Procedure: Urine Sample Collection Urine sample collection prior to radiation therapy, during last week of radiation therapy, 3 months and 2 years post-radiation therapy. Procedure: Blood Sample Collection Plasma and Serum sample collection prior to radiation therapy, during last week of radiation therapy, 3 months and 2 years post-radiation therapy. Behavioral: EPIC SF-12 Questionnaire Expanded Prostate Cancer Index Composite-Sf12 (EPIC SF12) quality of life questionnaire prior to radiation therapy, during last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months and yearly to 5.25. years post-radiation therapy. Behavioral: MAC-PC Questionnaire Memory Anxiety Scale for Prostate Cancer patients (MAX-PC) questionnaire prior to radiation therapy, during last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months and yearly to 5.25. years post-radiation therapy.
Active Comparator: Arm II: MTSRT Mapped Tumor Salvage RT (MTSRT)	Radiation: Mapped Tumor Salvage RT (MTSRT) Patients will receive the same treatment to the CTV of 68 Gy in 34 fractions and the GTV defined by DCE-MRI will receive 2.2 Gy per day for a total of 74.8 Gy (biological equivalent to 77.5 Gy in 2.0 Gy fractions assuming an α/β ratio of 3). Procedure: DCE-MRI of Pelvis/Prostate Dynamic Contrast Enhanced-MRI of the Pelvis/Prostate prior to radiation therapy, 3 months, 9 months and 2 years post-radiation therapy Procedure: Bone Scan Bone scan prior to radiation therapy for a PSA of >= 2 or physician concern for metastasis. Procedure: Ultrasound Prostate Bed Biopsy Ultrasound Prostate Bed Biopsy prior to radiation therapy; 2 - 2.5 years post radiation therapy. Procedure: Urine Sample Collection Urine sample collection prior to radiation therapy, during last week of radiation therapy, 3 months and 2 years post-radiation therapy. Procedure: Blood Sample Collection Plasma and Serum sample collection prior to radiation therapy, during last week of radiation therapy, 3 months and 2 years post-radiation therapy. Behavioral: EPIC SF-12 Questionnaire Expanded Prostate Cancer Index Composite-Sf12 (EPIC SF12) quality of life questionnaire prior to radiation therapy, during last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months and yearly to 5.25. years post-radiation therapy. Behavioral: MAC-PC Questionnaire Memory Anxiety Scale for Prostate Cancer patients (MAX-PC) questionnaire prior to radiation therapy, during last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months and yearly to 5.25. years post-radiation therapy.

Arms

Assigned Interventions

Active Comparator: Arm I: SSRT

Standard Salvage Radiation Treatment (SSRT)

Radiation: Standard Salvage Radiation Treatment (SSRT)

Patients will receive 68 Gy in 2 Gy fractions to the prostate bed clinical target volume (CTV).

Procedure: DCE-MRI of Pelvis/Prostate

Dynamic Contrast Enhanced-MRI of the Pelvis/Prostate prior to radiation therapy, 3 months, 9 months and 2 years post-radiation therapy

Procedure: Bone Scan

Bone scan prior to radiation therapy for a PSA of >= 2 or physician concern for metastasis.

Procedure: Ultrasound Prostate Bed Biopsy

Ultrasound Prostate Bed Biopsy prior to radiation therapy; 2 - 2.5 years post radiation therapy.

Procedure: Urine Sample Collection

Urine sample collection prior to radiation therapy, during last week of radiation therapy, 3 months and 2 years post-radiation therapy.

Procedure: Blood Sample Collection

Plasma and Serum sample collection prior to radiation therapy, during last week of radiation therapy, 3 months and 2 years post-radiation therapy.

Behavioral: EPIC SF-12 Questionnaire

Expanded Prostate Cancer Index Composite-Sf12 (EPIC SF12) quality of life questionnaire prior to radiation therapy, during last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months and yearly to 5.25. years post-radiation therapy.

Behavioral: MAC-PC Questionnaire

Memory Anxiety Scale for Prostate Cancer patients (MAX-PC) questionnaire prior to radiation therapy, during last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months and yearly to 5.25. years post-radiation therapy.

Active Comparator: Arm II: MTSRT

Mapped Tumor Salvage RT (MTSRT)

Radiation: Mapped Tumor Salvage RT (MTSRT)

Patients will receive the same treatment to the CTV of 68 Gy in 34 fractions and the GTV defined by DCE-MRI will receive 2.2 Gy per day for a total of 74.8 Gy (biological equivalent to 77.5 Gy in 2.0 Gy fractions assuming an α/β ratio of 3).

Procedure: DCE-MRI of Pelvis/Prostate

Dynamic Contrast Enhanced-MRI of the Pelvis/Prostate prior to radiation therapy, 3 months, 9 months and 2 years post-radiation therapy

Procedure: Bone Scan

Bone scan prior to radiation therapy for a PSA of >= 2 or physician concern for metastasis.

Procedure: Ultrasound Prostate Bed Biopsy

Ultrasound Prostate Bed Biopsy prior to radiation therapy; 2 - 2.5 years post radiation therapy.

Procedure: Urine Sample Collection

Urine sample collection prior to radiation therapy, during last week of radiation therapy, 3 months and 2 years post-radiation therapy.

Procedure: Blood Sample Collection

Plasma and Serum sample collection prior to radiation therapy, during last week of radiation therapy, 3 months and 2 years post-radiation therapy.

Behavioral: EPIC SF-12 Questionnaire

Expanded Prostate Cancer Index Composite-Sf12 (EPIC SF12) quality of life questionnaire prior to radiation therapy, during last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months and yearly to 5.25. years post-radiation therapy.

Behavioral: MAC-PC Questionnaire

Memory Anxiety Scale for Prostate Cancer patients (MAX-PC) questionnaire prior to radiation therapy, during last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months and yearly to 5.25. years post-radiation therapy.

Eligibility

Ages Eligible for Study:	35 Years to 85 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Prostate cancer patients with a PSA after prostatectomy of at least 0.1 ng/mL and up to 3.0 ng/mL within 8 weeks 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.
MRI detectable lesion in prostate bed. DCE-MRI enhancing lesion in the prostate bed should be at least 0.4 cc and a maximum of 6 cc and was obtained ≤ 8 weeks prior to enrollment.
No evidence of metastatic (regional or distant) disease on the pelvic MRI.
Negative bone scan if deemed necessary by treating physician obtained ≤ 4 months prior to enrollment.
No previous pelvic radiotherapy.
Prior androgen deprivation therapy is permitted as long as it was >6 months previous to enrollment and was ≤7 months in duration.
Serum total testosterone is within 40% of normal assay limits, taken within 4 months prior to enrollment.
BUN and creatinine is within 40% of normal assay limits, taken within 8 weeks 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 ≥ 5 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:

Prostate cancer patients with a PSA after prostatectomy of less than 0.1 ng/mL or greater than 3.0 ng/mL.
Less than 3 months since prostatectomy.
Unable to obtain a 3T MRI of the pelvis and prostate with contrast prior to enrollment.
No detectable MRI lesion in prostate bed.
Patients with detectable DCE-MRI lesion which are less than 0.4 cc and greater than 6 cc
Evidence of metastatic (regional or distant) disease on the pelvic MRI.
Positive bone scan 4 months prior to enrollment.
Previous pelvic radiotherapy.
Prior androgen deprivation therapy is not permitted if it was within 6 months previous to enrollment and/or was > 7 months in duration.
Serum total testosterone is not within 40% of normal assay limits, taken within 4 months prior to enrollment.
BUN and creatinine is not within 40% of normal assay limits, taken within 8 weeks prior to enrollment.
Concurrent, active malignancy, which is not nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for < 5 years then the patient is not eligible.
Inability to understand and unwilling to sign a written informed consent document.
Zubrod performance status ≥ 2.
Not willing to fill out quality of life/psychosocial questionnaires.
Age < 35 and > 85 years.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01411345

Locations

United States, Florida
University of Miami Sylvester Comprehensive Cancer Center	Recruiting
Miami, Florida, United States, 33136
Contact: Matthew C Abramowitz, MD 305-243-4200 mabramowitz@med.miami.edu
Contact: University of Miami Sylvester Comprehensive Cancer Center 866-574-5124 sylvester@emergingmed.com
Sub-Investigator: Alan Pollack, MD, PhD
Sub-Investigator: Javier Casillas, MD
Sub-Investigator: Ram Datar, MD
Sub-Investigator: Jennifer Hu, PhD
Sub-Investigator: Bruce Kava, MD
Sub-Investigator: Brian Lally, MD
Sub-Investigator: Charles Lynne, MD
Sub-Investigator: Murughesan Manoharan, MD
Sub-Investigator: Arnold Markoe, MD
Sub-Investigator: Mehrdad Nadji, MD
Sub-Investigator: Frank Penedo, PhD
Sub-Investigator: Lorraine Portelance, MD
Sub-Investigator: Michael Samuels, MD
Sub-Investigator: Rakesh Singal, MD
Sub-Investigator: Mark Soloway, MD
Sub-Investigator: Radka Stoyanova, PhD
Sub-Investigator: Cristiane Takita, MD
Sub-Investigator: Saleem Umar, MD
Sub-Investigator: Aaron Wolfson, MD
Sub-Investigator: Jean Wright, MD
Sub-Investigator: Xiaodong Wu, PhD

Sponsors and Collaborators

University of Miami Sylvester Comprehensive Cancer Center

Investigators

Principal Investigator:

Matthew C Abramowitz, MD

University of Miami Sylvester Comprehensive Cancer Center

More Information

No publications provided

Responsible Party:	University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT01411345 History of Changes
Other Study ID Numbers:	EPROST-20101056
Study First Received:	August 4, 2011
Last Updated:	May 20, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Miami Sylvester Comprehensive Cancer Center:

Prostate Cancer
Prostate Adenocarcinoma

Additional relevant MeSH terms:

Adenocarcinoma
Adenocarcinoma, Mucinous
Prostatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

Neoplasms, Cystic, Mucinous, and Serous
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on May 23, 2013