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

BACKGROUND:

Prostate cancer that recurs after prostatectomy (rising PSA) with no evidence of metastatic
disease is often treated with radiation to the entire prostate bed to a dose of 66-72 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

- 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.

- INCLUSION CRITERIA:

- Patients must have histologically or cytologically confirmed adenocarcinoma of the
prostate.

- Indications for post-prostatectomy radiation exist:

- Disease progression (detectable PSA on two measurements obtained at least one
month apart) or

- indications for adjuvant radiation exist (if undetectable PSA): pathologic T3,
T4, N+ disease or positive margins (within 1 year of prostatectomy).

- Age greater than or equal to 18 years.

- ECOG performance status less than or equal to 1 (Karnofsky greater than or equal to
60)

- Ability of subject to understand and the willingness to sign a written informed
consent document.

- Radiation is teratogenic; thus, men must agree to use adequate contraception (hormonal
or barrier method of birth control; abstinence) prior to study entry, for the duration
of study participation and up to 120 days after the last radiation. Should a woman
become pregnant or suspect she is pregnant while her partner is participating in this
study, she should inform her treating physician immediately.

- HIV positive patients are included if CD4+ T-cell count > 200 cells/uL; on stable
antiretroviral therapy for > 1 year with HIV viral load <200 copies/mL, and no history
of opportunistic infections in > 1 year.

EXCLUSION CRIETERIA:

- Patients who are receiving any other investigational agents concurrently.

- Documented metastases of prostate cancer outside of the pelvis (pelvic lymph nodes are
allowed only if within the prostate bed region).

- History of radiation that would overlap with the intended treatment to the prostate
bed.

- Known contraindications to radiation such as inflammatory bowel disease, active
systemic lupus or scleroderma, or radiation hypersensitivity syndrome (Ataxia
Telangiectasia or Fanconi s Anemia)

- Subjects with any coexisting medical or psychiatric condition which, in the opinion of
the Investigator likely to interfere with study procedures and/or results.

- Medically indicated use of known radiosensitizing drugs (such as protease inhibitors)