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

Primary Purpose

Prostate Cancer, Prostate Adenocarcinoma

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Lattice Extreme Ablative Dose Radiation Therapy

Standard IMRT

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

35 Years - 85 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Biopsy confirmed adenocarcinoma of the prostate.
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).
Gleason score 6-10.
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.
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.
No previous pelvic radiotherapy.
No previous history of radical/total prostatectomy (suprapubic prostatectomy is acceptable).
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.
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.
Ability to understand and the willingness to sign a written informed consent document.
Zubrod performance status < 2.
Willingness to fill out quality of life forms.
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.
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.
Serum liver function tests (LFT) are taken within 3 months of enrollment.
Complete blood counts are taken within 3 months of enrollment.
Age ≥ 35 and ≤ 85 years.

Exclusion Criteria:

> T3a disease on digital rectal exam or >T3a disease clearly identified by MRI.
Gleason score < 6.
≥ 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%.
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.
PSA > 30 ng/mL within 3 months of enrollment
Unable to obtain a 1.5T or 3.0T multiparametric MRI of the pelvis and prostate with contrast.
Unidentifiable multiparametric MRI tumor lesion.
Identifiable multiparametric-MRI tumor lesions, that total in volume ≥ 33% of the prostate.
Previous pelvic radiotherapy.
Previous history of radical prostatectomy.
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.
Zubrod performance status ≥ 2.
Inability to understand or unwilling to sign a written informed consent document
Unwilling to fill out quality of life/psychosocial forms.
Bone scan is positive and other imaging tests confirm a suspicion of metastasis from prostate cancer.
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).
Serum liver function tests (LFTs) are not taken within 3 months of enrollment.
Complete blood counts are not taken within 3 months of enrollment.
Age < 35 and > 85 years.

Sites / Locations

University of Miami

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LEAD Radiation Therapy

Arm Description

Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT01411319

First Posted

August 3, 2011

Last Updated

July 11, 2021

Sponsor

University of Miami

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01411319

Brief Title

MRI-Guided Lattice Extreme Ablative Dose Radiotherapy For Prostate Cancer

Acronym

LEAD

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Completed

Study Start Date

December 27, 2011 (Actual)

Primary Completion Date

December 31, 2014 (Actual)

Study Completion Date

March 2, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Miami

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The hypotheses of this study are: 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. 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.

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

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LEAD Radiation Therapy

Arm Type

Experimental

Arm Description

Participants in this group will receive the LEAD Radiation Therapy on Day 1 followed by 38 daily standard IMRT beginning Day 2.

Intervention Type

Radiation

Intervention Name(s)

Lattice Extreme Ablative Dose Radiation Therapy

Other Intervention Name(s)

LEAD RT

Intervention Description

12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1.

Intervention Type

Radiation

Intervention Name(s)

Standard IMRT

Other Intervention Name(s)

IMRT

Intervention Description

76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.

Primary Outcome Measure Information:

Title

Number of Study Participants Experiencing Treatment-Related Toxicity

Description

Time Frame

Up to 8.5 weeks

Title

Percentage of Enrolled Patients for Whom LEAD RT Dose Can be Successfully Administered Following MRI-guided Planning.

Description

The percentage of enrolled patients for whom LEAD RT dose can be successfully administered following MRI-guided planning.

Time Frame

Up to 8 weeks

Secondary Outcome Measure Information:

Title

Number of Participants With Remaining Tumor Cells in the Prostate Post Treatment

Description

The number of participants with positive tumor cells left in the prostate after LEAD RT as evaluated by prostate biopsy.

Time Frame

Up to 2.5 Years

Title

Percentage of Participants With Positive Prostate Biopsies After Completion of Treatment

Description

Preliminary indication of efficacy of treatment will be reported as the percentage of participants with positive prostate biopsies after completion of treatment.

Time Frame

From Baseline to 2.5 Years Post Completion of Study Therapy (Approximately 3 years)

Title

Rate of Participants That Achieve Failure-Free Survival (FFS)

Description

Time Frame

Up to 6 years

Title

Overall Survival (OS)

Description

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.

Time Frame

Up to 6 years

Title

HrQoL as Assessed by EPIC-SF12 Questionnaire

Description

Time Frame

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

Title

HrQoL as Assessed by MAX-PC Questionnaire

Description

Time Frame

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

35 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Biopsy confirmed adenocarcinoma of the prostate. 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). Gleason score 6-10. 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. 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. No previous pelvic radiotherapy. No previous history of radical/total prostatectomy (suprapubic prostatectomy is acceptable). 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. 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. Ability to understand and the willingness to sign a written informed consent document. Zubrod performance status < 2. Willingness to fill out quality of life forms. 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. 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. Serum liver function tests (LFT) are taken within 3 months of enrollment. Complete blood counts are taken within 3 months of enrollment. Age ≥ 35 and ≤ 85 years. Exclusion Criteria: > T3a disease on digital rectal exam or >T3a disease clearly identified by MRI. Gleason score < 6. ≥ 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%. 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. PSA > 30 ng/mL within 3 months of enrollment Unable to obtain a 1.5T or 3.0T multiparametric MRI of the pelvis and prostate with contrast. Unidentifiable multiparametric MRI tumor lesion. Identifiable multiparametric-MRI tumor lesions, that total in volume ≥ 33% of the prostate. Previous pelvic radiotherapy. Previous history of radical prostatectomy. 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. Zubrod performance status ≥ 2. Inability to understand or unwilling to sign a written informed consent document Unwilling to fill out quality of life/psychosocial forms. Bone scan is positive and other imaging tests confirm a suspicion of metastasis from prostate cancer. 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). Serum liver function tests (LFTs) are not taken within 3 months of enrollment. Complete blood counts are not taken within 3 months of enrollment. Age < 35 and > 85 years.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alan Pollack, MD, PhD

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

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32084522

Citation

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.

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MRI-Guided Lattice Extreme Ablative Dose Radiotherapy For Prostate Cancer

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