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Prostatic Neoplasms

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Genital Diseases, Male

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Radiation will be delivered at an escalated dose to areas of recurrent prostate cancer identified on imaging and a reduced dose will be delivered to the entire prostate bed.

Prostate bed with integrated boost

Radiation will be delivered to the prostate bed only.

Prostate bed irradiation only

Whole Body Bone Scan

18F-NaF PET Imaging

Computed tomography of the abdomen and pelvis if clinically indicated at screening, with oral and intravenous contrast.

mpMRI of the prostate bed at screening and 6 month follow up.

mpMRI

After enrollment if clinically indicated (i.e., anti-androgen, gonadotropin releasing hormone agonist, or combination of both).

Deborah E Citrin, M.D.

Background:

Sometimes prostate cancer comes back after a person's prostate is removed. In this case, radiation is a common treatment. Radiation kills prostate cancer cells. It can be very effective. It is usually given in short doses almost every day for 6 or 7 weeks. Researchers want to see if a shorter schedule can be as effective. They want to see if that causes the same or fewer side effects. Usually, radiation is used to treat the entire area where the prostate was before surgery. In some patients, an area of tumor can be seen on scans. Researchers are also trying to see if they can give less dose to the area usually treated with radiation if the full dose is given to the tumor seen on scans.

Objective:

To find the shortest radiation schedule that people can tolerate without strong side effects.

Eligibility:

People at least 18 years old who have had a prostatectomy and will get radiation.

Design:

Participants will be screened with:

* Medical history
* Physical exam
* Blood and urine tests
* Scan that uses a small amount of radiation to make a picture of the body
* Scan that uses a magnetic field to make an image of the body
* Participants will provide documents that confirm their diagnosis.
* Participants may have a scan of the abdomen and pelvis.

Before they start treatment, participants will have another physical exam and blood tests.

Participants will get radiation each day Monday through Friday. Treatment may last 2, 3, or 4 weeks.

Participants may provide a tissue sample from a previous procedure for research.

Participants will answer questions about their general well-being and function.

About 4-5 weeks after they finish radiation treatment, participants will have a follow-up visit. They will be examined and give a blood sample. They will have 6 follow-up visits for the next 2 years.

BACKGROUND:

Prostate cancer that recurs after prostatectomy (rising prostate-specific antigen (PSA) with no evidence of metastatic disease is often treated with radiation to the entire prostate bed to a dose of 66-72 Gray (Gy) over 6-7 weeks. This treatment can provide PSA control in approximately 75% of patients but may have associated genitourinary and gastrointestinal toxicity due to irradiation of the rectum, small bowel, and bladder. Imaging of prostate cancer has improved to the extent that recurrent disease is often identified in the prostate bed or in other pelvic sites. The current standard is to irradiate the entire prostate bed to the total dose. This trial will test the tolerability of accelerated treatment designed to yield a similar rate of late toxicity. In addition, in patients with visible tumor, it will test the feasibility of delivering a lower dose to the prostate bed and an integrated boost (simultaneous) to the visible tumor to allow a higher dose to visible tumor than can be delivered with standard approaches.

OBJECTIVE:

- Define the maximum tolerated dose (MTD) hypofractionation of image guided, focally dose escalated post-prostatectomy radiation.

ELIGIBILITY:

* PSA recurrence after prostatectomy or indications for adjuvant radiation after prostatectomy.
* No evidence of distant metastases of prostate cancer (pelvic lymph nodes are allowed).
* Age greater than or equal to 18 years old
* Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1

DESIGN:

This is a Phase I trial of hypofractionated focal dose escalation with reduced dose prostate bed irradiation using image and pathologic guidance. The prostate bed will be treated with hypofractionated radiation and areas in the prostate bed or pelvis shown to have tumor on biopsy or with advanced imaging studies will be treated with an integrated boost to visible tumor. The treatment duration will be decreased sequentially in three Dose Level groups. Quality of life and functional outcomes such as urine, bowel, and erectile function will be assessed with questionnaires. A maximum of 48 patients will be enrolled.

Highly Conformal, Hypofractionated, Focally Dose Escalated Post-Prostatectomy Radiotherapy

A Phase I Trial of Highly Conformal, Hypofractionated, Focally Dose Escalated Post-Prostatectomy Radiotherapy

All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

A DLT is defined as any of the following: Grade 3 rectal, small bowel, or urinary toxicity that does not resolve to Grade 2 or less within 4 days with appropriate medical management. Other grade 3 in-field toxicities attributable to radiation that does not resolve to Grade 2 or less within 4 days with appropriate medical management. And delays of more than one week in completing radiation treatment due to toxicity.

Maximum tolerated dose (MTD) of image guided hypofractionated, focally dose escalated post-prostatectomy radiation is defined as the dose level at which no more than 1 of up to 6 participants experience dose limiting toxicity (DLT) during the DLT period, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of treatment. A DLT is defined as any of the following: Grade 3 rectal, small bowel, or urinary toxicity that does not resolve to Grade 2 or less within 4 days with appropriate medical management. Other grade 3 in-field toxicities attributable to radiation that does not resolve to Grade 2 or less within 4 days with appropriate medical management. And delays of more than one week in completing radiation treatment due to toxicity.

bPFS is defined as the duration of time from start of treatment to time of prostate-specific antigen (PSA) progression or death, whichever occurs first. PSA progression (also known as biochemical failure) is defined based on elevation of PSA beyond 0.1 ng/dL. Kaplan-Meier survival analysis and effects of clinical variables on bPFS will be assessed by the Cox proportional hazards model.

The quality-of-life scores will be summarized at baseline and for each visit. Linear mixed effects model will be used to model quality of life scores at baseline and during and after treatment in which random intercept and random slope are used to account for participant-specific trajectory of quality-of-life scores.

Participants completed a 6-question questionnaire to assess erectile dysfunction.

The AUA-SI is used to measure radiation morbidity and to make treatment decisions.

Participants complete a form to assess negative mood (i.e., sadness, guilt), views of self (i.e., self-criticism, worthlessness) social cognition (loneliness, interpersonal alienation), decreased positive effect, and decreased engagement (loss of interest, meaning, and purpose) and are scored using item-level calibrations.

Participants complete a form and rate anxiety such as fear (fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, restlessness), and somatic symptoms related to arousal (racing heart, dizziness).

Participants complete a form to assess positive psychosocial (emotional and social) outcomes of illness.

The DRS is a 5-item scale measuring distress or remorse after a health case decision. The score correlated with satisfaction with the decision (r=-0.40 to -0.60), decisional conflict (r=0.31 to 0.52), and overall rated quality of life (r=-0.25 to -0.27).

Grade 2-5 serious and/or non-serious adverse events attributable to protocol treatment. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 2 is moderate. Grade 3 is serious. Grade 4 is life-threatening. And Grade 5 is death related to adverse event.

National Cancer Institute (NCI)

Investigator

LEVEL 1/COHORT 1: Recurrent tumor visible; prostate bed with integrated boost. 20 fractions: Dose to prostate bed 45.8 Gray (Gy) in 2.29 Gy fractions; Dose to tumor 60.4 Gy in 3.02 Gy fractions.

LEVEL 1/COHORT 1: Recurrent Tumor Visible; Prostate Bed With Integrated Boost - 20 Fractions

LEVEL 2/COHORT 1: Recurrent tumor visible, prostate bed with integrated boost. 15 fractions: Dose to prostate bed 41.85 Gray (Gy) in 2.79 Gy fractions; Dose to tumor 54.6 Gy in 3.64 Gy fractions.

LEVEL 2/COHORT 1: Recurrent Tumor Visible; Prostate Bed With Integrated Boost - 15 Fractions

LEVEL 3/COHORT 1: Recurrent tumor visible, prostate bed with integrated boost. 10 fractions: Dose to prostate bed 36.4 Gray (Gy) in 3.64 Gy fractions; Dose to tumor 47.1 Gy in 4.71 Gy fractions.

LEVEL 3/COHORT 1: Recurrent Tumor Visible; Prostate Bed With Integrated Boost - 10 Fractions

LEVEL 1/COHORT 2: Recurrent tumor NOT visible, prostate bed irradiation only. 20 fractions: Dose to prostate bed 56.4 Gray (Gy) in 2.82 Gy fractions.

LEVEL 1/COHORT 2: Recurrent Tumor NOT Visible; Prostate Bed Irradiation Only - 20 Fractions

LEVEL 2/COHORT 2: Recurrent tumor NOT visible, prostate bed irradiation only. 15 fractions: Dose to prostate bed 51.2 Gray (Gy) in 3.41 Gy fractions.

LEVEL 2/COHORT 2: Recurrent Tumor NOT Visible; Prostate Bed Irradiation Only - 15 Fractions

LEVEL 3/COHORT 2: Recurrent tumor NOT visible, prostate bed irradiation only. 10 fractions: Dose to prostate bed 44.2 Gray (Gy) in 4.42 Gy fractions.

LEVEL 3/COHORT 2: Recurrent Tumor NOT Visible; Prostate Bed Irradiation Only - 10 Fractions

LEVEL 1/ COHORT 1: Recurrent tumor visible; prostate bed with integrated boost. 20 fractions: Dose to prostate bed 45.8 Gray (Gy) in 2.29 Gy fractions; Dose to tumor 60.4 Gy in 3.02 Gy fractions.

LEVEL 1/ COHORT 1: Recurrent Tumor Visible; Prostate Bed With Integrated Boost - 20 Fractions

LEVEL 2/ COHORT 1: Recurrent tumor visible, prostate bed with integrated boost. 15 fractions: Dose to prostate bed 41.85 Gray (Gy) in 2.79 Gy fractions; Dose to tumor 54.6 Gy in 3.64 Gy fractions.

LEVEL 2/ COHORT 1: Recurrent Tumor Visible; Prostate Bed With Integrated Boost - 15 Fractions

LEVEL 3/ COHORT 1: Recurrent tumor visible, prostate bed with integrated boost. 10 fractions: Dose to prostate bed 36.4 Gray (Gy) in 3.64 Gy fractions; Dose to tumor 47.1 Gy in 4.71 Gy fractions.

LEVEL 3/ COHORT 1: Recurrent Tumor Visible; Prostate Bed With Integrated Boost - 10 Fractions

LEVEL 1/ COHORT 2: Recurrent tumor NOT visible, prostate bed irradiation only. 20 fractions: Dose to prostate bed 56.4 Gray (Gy) in 2.82 Gy fractions.

LEVEL 1/ COHORT 2: Recurrent Tumor NOT Visible; Prostate Bed Irradiation Only - 20 Fractions

LEVEL 2/ COHORT 2: Recurrent tumor NOT visible, prostate bed irradiation only. 15 fractions: Dose to prostate bed 51.2 Gray (Gy) in 3.41 Gy fractions.

LEVEL 2/ COHORT 2: Recurrent Tumor NOT Visible; Prostate Bed Irradiation Only - 15 Fractions

LEVEL 3/ COHORT 2: Recurrent tumor NOT visible, prostate bed irradiation only. 10 fractions: Dose to prostate bed 44.2 Gray (Gy) in 4.42 Gy fractions.

LEVEL 3/ COHORT 2: Recurrent Tumor NOT Visible; Prostate Bed Irradiation Only - 10 Fractions

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Deborah E. Citrin

Dose to prostate bed

Dose to tumor

All participants with recurrent tumor visible assessed for MTD.

Level 1 Cohort 1, Level 2 Cohort 1, and Level 3 Cohort 1:

Recurrent tumor visible, prostate bed with integrated boost. 10 fractions: Dose to prostate bed 36.4 Gray (Gy) in 3.64 Gy fractions; Dose to tumor 47.1 Gy in 4.71 Gy fractions.

All Participants With Recurrent Tumor Visible

All participants with recurrent tumor NOT visible assessed for MTD.

Level 1 Cohort 2, Level 2 Cohort 2, and Level 3 Cohort 2:

Recurrent tumor NOT visible, prostate bed irradiation only. 10 fractions: Dose to prostate bed 44.2 Gray (Gy) in 4.42 Gy fractions.

All Participants With Recurrent Tumor NOT Visible

12/30 expansion group participants (6 in Recurrent Tumor Visible: Level 3 Cohort 1, and Recurrent Tumor NOT Visible: Level 3 Cohort 2) were not assessed for MTD and included in the analysis.

Spots Global Cancer Trial Database for whole body bone scan