Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Adenocarcinoma

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

36.25 Gy IMRT in 5 fractions over two and a half weeks

51.6 Gy IMRT in 12 fractions over two and a half weeks

36.25 Gy in 5 fractions of 7.5 Gy twice a week over 15-17 days. A minimum of 72 hours and a maximum of 96 hours will separate each treatment. IMRT or similar techniques that use inverse treatment planning or protons are required.

36.25 Gy IMRT

51.6 Gy in 12 fractions of 4.3 Gy 5 days a week over 16-18 days. IMRT or similar techniques that use inverse treatment planning or protons are required.

51.6 Gy IMRT

Himu R. Lukka, MD

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Given radiation therapy in different ways may kill more tumor cells.

PURPOSE: This randomized phase II trial studies radiation therapy to see how well it works in treating patients with prostate cancer.

OBJECTIVES:

Primary

* To demonstrate that 1-year health-related quality of life (HRQOL) for at least one hypofractionated arm is not significantly lower than baseline as measured by the Bowel and Urinary domains of the Expanded Prostate Cancer Index Composite (EPIC) instrument.

Secondary

* To estimate the degree of change in HRQOL in each arm for the Sexual and Hormonal EPIC domains and the Utilization of Sexual Medications/Devices from baseline to 1 year, 2 years, and 5 years.
* To estimate the degree of change in global HRQOL in each arm as measured by the Euro Quality of Life, 5 dimensions (EQ-5D) from baseline to 1 year, 2 years, and 5 years.
* To estimate the rate of acute and late gastrointestinal (GI) and genitourinary (GU) toxicity for each arm at 1, 2, and 5 years.
* To estimate prostate-specific antigen (PSA) failure in each arm at 1, 2, and 5 years.
* To estimate disease-free survival (DFS) in each arm at 1, 2, and 5 years.
* To estimate Quality Adjusted Life Years for each arm at 1, 2, and 5 years using the EQ-5D and DFS.
* To identify genetic markers associated with normal tissue toxicities resulting from radiotherapy.
* To collect tumor tissue for biomarker studies.
* To estimate EPIC bowel and urinary HRQOL as continuous variables.

OUTLINE: This is a multicenter study. Patients are stratified according to treatment techniques/machine (all linear accelerator-based treatment \[excluding cyberknife\] vs cyberknife vs protons). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo hypofractionated radiotherapy using intensity-modulated radiation therapy (IMRT), cyberknife, or protons twice a week for approximately 2½ weeks (36.25 Gy total).
* Arm II: Patients undergo hypofractionated radiotherapy using IMRT, cyberknife, or protons once a day, 5 days a week, for approximately 2½ weeks (51.6 Gy total).

Patients may undergo blood and tumor tissue collection for correlative studies.

Patients may also complete the Utilization of Sexual Medications/Devices, the European Questionnaire-5D, and the Bowel and Urinary domains of the Expanded Prostate Cancer Index Composite (EPIC) questionnaires at baseline and at 1, 2, and 5 years after completion of radiation therapy.

After completion of study therapy, patients are followed-up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Radiation Therapy in Treating Patients With Prostate Cancer

A Randomized Phase II Trial of Hypofractionated Radiotherapy for Favorable Risk Prostate Cancer

The co-primary endpoint is the percentage of patients with a reduction in the Expanded Prostate Cancer Index Composite (EPIC) bowel domain score from baseline to 1 year that exceeds 5 points (baseline - one year \> 5). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.

The co-primary endpoint is the proportion of patients with a reduction in the Expanded Prostate Cancer Index Composite (EPIC) urinary domain score from baseline to 1 year that exceeds 2 points (baseline - one year \> 2). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.

Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. An acute adverse event is defined as the first occurrence of worst severity of the adverse event ≤30 days after the completion of radiation therapy (RT). The high dose RT arm of Radiation Therapy Oncology Group (RTOG) study RTOG-0126 (NCT00033631) reported 1% of patients experienced grade 3+ GI/GU acute toxicity with no patient experiencing a grade 4 or 5 toxicity. If the lower confidence interval is \>1%, then that arm will be further investigated for acceptability. A late adverse event is defined as the first occurrence of worst severity of adverse event \>30 days after RT completion. Arms are not compared to each other.

Failure occurs when the PSA is first noted to be 2 ng/mL or more than the current nadir value (PSA \> current nadir + 2) post RT completion. Time to PSA failure is defined as time from registration to the date of PSA failure, last known follow-up (censored), or death without PSA failure (competing risk). Rate of PSA failure is estimated by the cumulative incidence method. The protocol specified that one-, two-, and five-year rates would be reported. Arms are not compared to each other.

Disease-free survival duration is time from the date of randomization to the date of documentation of disease progression or until the date of death from any cause (censored). DFS is estimated by the Kaplan-Meier method. The protocol specified that one-, two-, and five-year rates would be reported. Arms are not compared to each other.

Quality-adjusted survival time combines disease-free survival time and quality of life as measured by the EuroQol 5-dimensional (EQ-5D) index score. It is calculated for each patient as the weighted sum of different time episodes and added up to total quality-adjusted life years . The EQ-5D measures health-related quality of life and consists of two parts, a general health visual analog scale and 5 general health questions. The latter questions are transformed into a single index score ranging from 0 (worst health state) to 1 (best health state). Arms are not compared to each other.

The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life and a positive change from baseline indicating improvement over time. For this endpoint, in each domain, the actual change score calculated as timepoint score - baseline score will be used as the statistic.

The percentage of patients with a reduction in the EPIC sexual domain score from baseline that exceeds 11 points (baseline - one year \> 11). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.

The percentage of patients with a reduction in the EPIC hormonal domain score from baseline that exceeds 3 points (baseline - one year \> 3). The EPIC is a 50-item, validated tool to assess disease-specific aspects of prostate cancer and its therapies and comprises of four summary domains (bowel, urinary, sexual, and hormonal). Response options for each EPIC item form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life. Arms are not compared to each other.

The EQ-5D is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). Health states are defined by the combination of the leveled responses to the 5 dimensions, generating 243 health states to which unconsciousness and death are added. The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). Change from baseline is calculated as score at the timepoint of interested - baseline score. One, 2, and 5 years will be entered when they are available. Arms are not compared.

The Utilization of Sexual Medications/Devices questionaire is designed to assess the use of erectile aids among patients treated for prostate cancer. This instrument is used to complement the sexual symptom domain in the EPIC. The number of subjects responding "Yes" to the following questions are reported: "Do you have a penile prosthesis", "Have you used an medications or devices to aid or improve erections?". Arms are not compared to each other. One, 2, and 5 years will be entered when they are available.

National Cancer Institute (NCI)

NRG Oncology

Radiation Therapy Oncology Group

Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with adverse event data are included.

5 Fractions

12 Fractions

Total

Age, Continuous

Sex: Female, Male

Eligible patients who started protocol treatment

Wendy Seiferheld, M.S.

≤35% was considered acceptable, ≥55% unacceptable. Each arm analyzed separately. Average score and standard error of each arm calculated and one-sample z-test for proportion with significance level of 0.025 was used. For a given arm, if the null hypothesis of p ≤ 0.35 is rejected, then conclude that the regimen given on that arm is unacceptable. However if it not rejected for both bowel \& urinary domains, then that regimen will be considered acceptable for further use in a Phase III study.

Eligible patients who started protocol treatment and completed the bowel domain of the EPIC at baseline and one year

Percentage of Patients With Reduction From Baseline to the One-year EPIC Bowel Domain Score That Exceeds 5 Points

≤40% was considered acceptable, ≥60% unacceptable. Each arm analyzed separately. Average score and standard error of each arm calculated and one-sample z-test for proportion with significance level of 0.025 was used. For a given arm, if the null hypothesis of p ≤ 0.40 is rejected, then conclude that the regimen given on that arm is unacceptable. However if it not rejected for both bowel \& urinary domains, then that regimen will be considered acceptable for further use in a Phase III study.

Eligible patients who started protocol treatment and completed the urinary domain of the EPIC at baseline and one year

The Percentage of Patients With Reduction From Baseline to One-year EPIC Urinary Domain Score That Exceeds 2 Points

Acute

Late

Acute and Late Gastrointestinal (GI) and Genitourinary (GU) Toxicity for Each Arm

One year

Two years

Five years

Eligible patients who started protocol treatment and were at risk at the given time point

Rate of PSA Failure

Rate of Disease-free Survival (DFS)

Eligible patients who started protocol treatment with baseline EQ-5D and at least 1 follow-up assessment (EQ-5D Index Score)

Mean Quality Adjusted Life Years at 5 Years

\[Bowel one-year results\] Originally the t-test was planned to test if the change in each arm is different from 0. Wilcoxon Mann-Whitney was used instead due to the normality of the data.

\[Urinary one-year results\] Originally the t-test was planned to test if the change in each arm is different from 0. Wilcoxon Mann-Whitney was used instead due to the normality of the data.

1-year Bowel

1-year Urinary

Eligible patients who started protocol treatment and completed the respective domain of the EPIC at baseline and one year

Change From Baseline in EPIC Bowel and Urinary HRQOL as Continuous Variables at One Year

≤35% was considered acceptable, ≥55% unacceptable. Each arm analyzed separately. Average score and standard error of each arm calculated and one-sample z-test for proportion with significance level of 0.025 was used.

Eligible patients who started study treatment and completed the specified domain of the EPIC at baseline and one year

The Percentage of Patients With Reduction From Baseline at One Year in EPIC Sexual Domain Score That Exceeds 11 Points

≤38% was considered acceptable, ≥58% unacceptable. Each arm analyzed separately. Average score and standard error of each arm calculated and one-sample z-test for proportion with significance level of 0.025 was used.

The Percentage of Patients With Reduction From Baseline at One Year in EPIC Hormonal Domain Score That Exceeds 3 Points

\[One-year Index Score\] Originally the t-test was planned to test if the change in each arm is different from 0. Wilcoxon Mann-Whitney was used instead due to the non-normality of the data. Each arm analyzed separately.

\[One-year VAS Score\] Originally the t-test was planned to test if the change in each arm is different from 0. Wilcoxon Mann-Whitney was used instead due to the non-normality of the data. Each arm analyzed separately.

1-year Index Score

1-year VAS

All eligible patients who started study treatment and completed the EQ-5D at baseline and the specified timepoint

Change From Baseline in EQ-5D Scores

Baseline penile prosthesis question

Baseline medications/devices question

1-year penile prosthesis question

1-year Baseline medications/devices question

Eligible patients who started study treatment and completed the questionnaire at baseline and the specified timepoint

Utilization of Sexual Medications/Devices Questionnaire Response Frequences

36.25 Gy IMRT (intensity modulated radiation therapy) in 5 fractions over two and a half weeks

The biomarker data will not be obtained due to lack of funding therefore no patients have outcome measure data.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Radiation Therapy in Treating Patients With Prostate Cancer	NCT01434290	Prostate Cancer Psychosocial Ef... Radiation Toxic... Sexual Dysfunct...	36.25 Gy IMRT 51.6 Gy IMRT	18 Years -	Radiation Therapy Oncology Group
Radiation Therapy in Treating Patients With Prostate Cancer	NCT01434290	Prostate Cancer Psychosocial Ef... Radiation Toxic... Sexual Dysfunct...	36.25 Gy IMRT 51.6 Gy IMRT	18 Years -	Radiation Therapy Oncology Group

Spots Global Cancer Trial Database for 36.25 gy imrt