MRI-Guided Lattice Extreme Ablative Dose Radiotherapy For Prostate Cancer (LEAD)

A Phase I Trial of MRI-Guided Lattice Extreme Ablative Dose Radiotherapy For Prostate Cancer

The hypotheses of this study are:

1. Delivery of single fraction Lattice Extreme Ablative Dose (LEAD) radiotherapy (RT) to the dominant tumor lesion(s) in the prostate as identified by multiparametric functional Magnetic Resonance Imaging is safe and feasible when given prior to standard prostate radiotherapy.
2. Biomarker expression levels differ in the functional MRI identified suspicious tumor regions and unsuspicious tumor regions. The investigators hypothesize that a significant source of variation in biomarker levels is due to tumor heterogeneity and that it is molecular abnormalities in the dominant tumor areas that are angiogenic and determine outcome.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer; Prostate Adenocarcinoma
• Intervention / Treatment: Radiation: Lattice Extreme Ablative Dose Radiation Therapy; Radiation: Standard IMRT

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Biopsy confirmed adenocarcinoma of the prostate.

2. T1-T3a disease based on digital rectal exam (DRE).

   • T3a disease based on MRI is acceptable (no evidence of frank (clear cut) seminal vesicle (SV) involvement or invasion of bladder or rectum).
3. Gleason score 6-10.

4. Patients with Gleason score ≥8 must be offered long term androgen deprivation therapy (ADT) and refuse such treatment because only 4-6 months (+/- 2 months) (short term ADT) is permitted (not required) on this protocol. The ADT is recommended to begin after fiducial marker placement; however, ADT is permitted to have been started up to two months prior to the signing of consent. All patients in this protocol may (not required) be treated with 4-6 months (+/- 2 months) of ADT, at the discretion of the treating physician.

   • Gleason ≥ 8 must have < 40% of the tissue involved with Gleason 8 in the biopsy specimen.
5. Prostate-specific antigen (PSA) ≤ 30 ng/mL within 3 months of enrollment. If PSA was above 30 and dropped to ≤ 30 with antibiotics, this is acceptable for enrollment.
6. No previous pelvic radiotherapy.
7. No previous history of radical/total prostatectomy (suprapubic prostatectomy is acceptable).
8. 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.

9. Identifiable multiparametric-MRI tumor lesion or lesions, that total in volume < 33% of the prostate

   • Multiparametric MRI of prostate and pelvis is required prior to protocol consideration.
   • If contrast not given, the point dose on the apparent diffusion coefficient (ADC) map should be < 1000.
10. Ability to understand and the willingness to sign a written informed consent document.
11. Zubrod performance status < 2.
12. Willingness to fill out quality of life forms.
13. Bone scan negative if PSA > 15 ng/mL or Gleason ≥ 8 disease. A questionable bone scan is acceptable if other imaging tests are negative for metastasis.
14. Serum testosterone is within 40% of normal assay limits (e.g., x=0.4*lower assay limit and x=.04*upper assay limit + upper assay limit), and taken within 4 months of enrollment. Patients who have been started on ADT prior to signing consent are not required to have a serum testosterone at this level prior to signing consent; but, a serum testosterone prior to fiducial marker placement is recommended.
15. Serum liver function tests (LFT) are taken within 3 months of enrollment.
16. Complete blood counts are taken within 3 months of enrollment.
17. Age ≥ 35 and ≤ 85 years.

Exclusion Criteria:

1. > T3a disease on digital rectal exam or >T3a disease clearly identified by MRI.
2. Gleason score < 6.
3. ≥ 40% Gleason 8-10 tumor, over the total tissue including other tumor and normal tissue. For example: (Gleason 8-10 tumor length/other biopsy tissue length)*100 = ≥ 40%.
4. Androgen deprivation therapy longer than 8 months. Androgen deprivation timing is for the Luteinizing hormone-releasing hormone (LHRH) agonist portion only and not when anti-androgen is started beforehand with the purpose of counteracting the surge in testosterone from the LHRH agonist - PSA > 30 ng/mL within 3 months of enrollment.
5. PSA > 30 ng/mL within 3 months of enrollment
6. Unable to obtain a 1.5T or 3.0T multiparametric MRI of the pelvis and prostate with contrast.
7. Unidentifiable multiparametric MRI tumor lesion.
8. Identifiable multiparametric-MRI tumor lesions, that total in volume ≥ 33% of the prostate.
9. Previous pelvic radiotherapy.
10. Previous history of radical prostatectomy.
11. 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.
12. Zubrod performance status ≥ 2.
13. Inability to understand or unwilling to sign a written informed consent document
14. Unwilling to fill out quality of life/psychosocial forms.
15. Bone scan is positive and other imaging tests confirm a suspicion of metastasis from prostate cancer.
16. Serum testosterone is not within 40% of normal assay limits taken within 4 months of enrollment (only applicable to patients not started on ADT prior to signing consent).
17. Serum liver function tests (LFTs) are not taken within 3 months of enrollment.
18. Complete blood counts are not taken within 3 months of enrollment.
19. Age < 35 and > 85 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LEAD Radiation Therapy; Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2.	Radiation: Lattice Extreme Ablative Dose Radiation Therapy; 12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1.; Other Names: LEAD RT; Radiation: Standard IMRT; 76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.; Other Names: IMRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Study Participants Experiencing Treatment-Related Toxicity	Toxicity are any Grade 2 or higher treatment-related adverse events as assessed by treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0.	Up to 8.5 weeks
Percentage of Enrolled Patients for Whom LEAD RT Dose Can be Successfully Administered Following MRI-guided Planning.	The percentage of enrolled patients for whom LEAD RT dose can be successfully administered following MRI-guided planning.	Up to 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Remaining Tumor Cells in the Prostate Post Treatment	The number of participants with positive tumor cells left in the prostate after LEAD RT as evaluated by prostate biopsy.	Up to 2.5 Years
Percentage of Participants With Positive Prostate Biopsies After Completion of Treatment	Preliminary indication of efficacy of treatment will be reported as the percentage of participants with positive prostate biopsies after completion of treatment.	From Baseline to 2.5 Years Post Completion of Study Therapy (Approximately 3 years)
Rate of Participants That Achieve Failure-Free Survival (FFS)	The percentage of participants achieving FFS will be reported. Failure-free is defined as no documented evidence of biochemical and/or or clinical failure or death from any cause, whichever occur first. Biochemical failure is defined is a increase of 2 or greater from nadir of Prostate Specific Antigen (PSA) levels. Clinical Failure is defined as newly identified extension outside the prostate after initial regression, or urinary obstructive symptoms with carcinoma or regional/distant failure due to radiographic evidence metastasis.	Up to 6 years
Overall Survival (OS)	Overall survival is defined as the elapsed time from study enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact.	Up to 6 years
HrQoL as Assessed by EPIC-SF12 Questionnaire	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. The questionnaire has 5 subscales (Urinary Function, Urinary Symptoms, Bowel Habits, Sexual Function and Hormonal Function). Each subscale has a total score ranging from 0-100, with higher scores representing better HRQOL.	At Baseline (Prior to RT), at 8 weeks (Last week of RT), At 6 weeks post RT, At 3 months post RT, At 6 months post RT, At 9 months post RT, At 15 months post RT, At 27 months post RT, At 39 months post RT, At 51 months post RT, At 63 months post RT
HrQoL as Assessed by MAX-PC Questionnaire	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.	At Baseline (Prior to RT), at 8 weeks (Last week of RT), At 6 weeks post RT, At 3 months post RT, At 6 months post RT, At 9 months post RT, At 15 months post RT, At 27 months post RT, At 39 months post RT, At 51 months post RT, At 63 months post RT

Collaborators and Investigators

• Sponsor: University of Miami
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Pollack A, Chinea FM, Bossart E, Kwon D, Abramowitz MC, Lynne C, Jorda M, Marples B, Patel VN, Wu X, Reis I, Studenski MT, Casillas J, Stoyanova R. Phase I Trial of MRI-Guided Prostate Cancer Lattice Extreme Ablative Dose (LEAD) Boost Radiation Therapy. Int J Radiat Oncol Biol Phys. 2020 Jun 1;107(2):305-315. doi: 10.1016/j.ijrobp.2020.01.052. Epub 2020 Feb 19. Erratum In: Int J Radiat Oncol Biol Phys. 2020 Sep 1;108(1):328.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 27, 2011
• Primary Completion (ACTUAL): December 31, 2014
• Study Completion (ACTUAL): March 2, 2020

Study Registration Dates

• First Submitted: August 3, 2011
• First Submitted That Met QC Criteria: August 5, 2011
• First Posted (ESTIMATE): August 8, 2011

Study Record Updates

• Last Update Posted (ACTUAL): July 13, 2021
• Last Update Submitted That Met QC Criteria: July 11, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 20100389; R21CA153826 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes