Patients will be accrued in alternating dose levels. The two distinct areas of dose
escalations (pelvic lymph node and prostate lesion) will take place one at a time. Minimum
waiting periods will be assigned between each dose cohort to observe toxicity. The phase I
portion of the study will be completed when dose limiting toxicity is reached or when a
sufficiently high dose level (i.e.,5.5 Gy per fraction to a total 27.5 Gy for pelvic lymph
node region and 11Gy per fraction to a total of 55Gy to the prostate lesion), is attained to
consider the therapy likely to be efficacious. All patients will be treated with a total of
24 months of androgen suppression therapy (ADT). Radiation therapy will start 8-12 weeks
after initiation of ADT.
No. Patients for each cohort: 7-15 Cohort 1: 9.5 Gy per fraction to prostate/SV, 10 Gy per
fraction to prostate lesion, 4.5Gy per fraction to pelvic lymph node region for 5 fractions
for a total of 47.5 / 50 / 22.5 Gy to Prostate+SV /Prostate lesions/Nodes Cohort 2: 9.5 Gy
per fraction to prostate/SV, 10 Gy per fraction to prostate lesion, 5Gy per fraction to
pelvic lymph node region for 5 fractions for a total of 47.5 / 50 / 25 Gy to Prostate+SV
/Prostate lesions/Nodes Cohort 3: 9.5 Gy per fraction to prostate/SV, 10.5 Gy per fraction to
prostate lesion, 5Gy per fraction to pelvic lymph node region for 5 fractions for a total of
47.5 / 52.5 / 25 Gy to Prostate+SV /Prostate lesions/Nodes Cohort 4: 9.5 Gy per fraction to
prostate/SV, 10.5 Gy per fraction to prostate lesion, 5.5 Gy per fraction to pelvic lymph
node region for 5 fractions for a total of 47.5 / 52.5 / 27.5 Gy to Prostate+SV /Prostate
lesions/Nodes Cohort 5: 9.5 Gy per fraction to prostate/SV, 11 Gy per fraction to prostate
lesion, 5.5 Gy per fraction to pelvic lymph node region for 5 fractions for a total of 47.5 /
55 / 27.5 Gy to Prostate+SV /Prostate lesions/Nodes
Inclusion Criteria:
- Signed study specific informed consent form.
- Patients must have at least one of the following criteria:
- The serum PSA should be greater than or equal to 20 ng/ml OR
- Study entry PSA must not be obtained during the following time frames:
1. 10-day period following prostate biopsy;
2. following initiation of ADT.
- The Gleason score should be greater than or equal to 8 OR
- Eligible patients must have appropriate staging studies identifying them as AJCC stage
T3+ adenocarcinoma of the prostate gland. (MR stage T3a without other high risk
factors permitted at investigator discretion
- Male Patient past their 18th birthday at time of registration.
- The patient's Zubrod performance status must be 0-2
- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, and
during radiation treatment.
- All patients must be willing and capable to provide informed consent to participate in
the protocol
- Imaging studies can include, but is not limited to the following: ultrasound, CT of
pelvis/prostate (abdomen recommended) and MRI of pelvis/prostate and (abdomen
recommended)
- The ultrasound, MRI or CT based volume estimation of the patient's prostate gland
should not be greater than 80 grams (Repeat measurement after hormone downsizing
allowed)
- Clinically negative lymph nodes, within 90 days of study enrollment, established by
imaging (pelvic/prostate (abdominal recommended) CT or MRI) OR by nodal sampling OR by
dissection. Nodes > 2.0 cm should be biopsied. Patients with lymph nodes equivocal or
questionable by imaging are eligible if the nodes are < 2.0cm in the short axis.
- MRI Pelvis/Prostate feasible for staging and planning
- Patients with contraindications to MRI are not eligible
- Patient deemed eligible for complete androgen blockade, and androgen deprivation
therapy by treating physician (this includes consideration of baseline liver function
prior to initiation of therapy, if necessary at physician's discretion). For patients
not eligible for anti-testosterone therapy, hormone therapy with LHRH agonist alone
will be permitted on case by case by study Principal Investigator. AS can be any LHRH
agonists, LHRG antagonists or anti-androgens that are approved for androgen
suppression for the treatment of prostate cancer.
- Patient does not have known allergy to polyethylene glycol hydrogel (spacer material).
- Patient deemed eligible for rectal spacer ( Space OAR) placement by treating
physician.
- Histologic confirmation of diagnosis of adenocarcinoma of the prostate will be
required by biopsy.
Exclusion Criteria:
- Eligible patients should not have had previous pelvic radiotherapy, chemotherapy or
surgery for prostate cancer.
- There must be no plans for the patient to receive other concomitant or post treatment
adjuvant antineoplastic therapy while on this protocol including surgery, cryotherapy,
conventionally fractionated radiotherapy, 2nd generation anti-androgen therapy (i.e
Enzalutamide, Abiraterone, etc.),or chemotherapy given as part of the treatment of
prostate cancer.
- The patient should not have direct evidence of regional or distant metastases after
appropriate staging studies, including no distant metastases (M0) on bone scan within
90 days of study enrollment. Equivocal bone scan findings are allowed if plain films
are negative for metastasis. PET or PSMA scans can be performed instead of a bone
scan.
- Patients diagnosed with invasive malignancy are not eligible (except non-melanomatous
skin cancer) unless disease free for a minimum of 3 years (e.g., oral cavity).
- Patients diagnosed with severe, active co-morbidity, defined as follows are not
eligible:
- Unstable angina and/or congestive heart failure requiring hospitalization within the
last 6 months.
- Transmural myocardial infarction within the last 6 months.
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of
registration.
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days before
registration.
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note,
however, that laboratory tests for liver function and coagulation parameters are not
required for entry into this protocol.
- Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note,
however, that HIV testing is not required for entry into this protocol. The need to
exclude patients with AIDS from this protocol is necessary because the treatments
involved in this protocol may be significantly immunosuppressive. Protocol-specific
requirements may also exclude immuno-compromised patients.
- Patients with history of inflammatory colitis (including Crohn's Disease and
Ulcerative colitis), active lupus, and scleroderma or active collagen vascular disease
are not eligible.
- Patients should not have undergone previous transurethral resection of the prostate
(TURP) within 1 year.
- Patients with history of inflammatory colitis (including Crohn's Disease and
Ulcerative colitis) are not eligible.
- Eligible patients should not have had previous pelvic radiotherapy, chemotherapy or
surgery for prostate cancer.
- There must be no plans for the patient to receive other concomitant or post treatment
adjuvant antineoplastic therapy while on this protocol including surgery, cryotherapy,
conventionally fractionated radiotherapy, 2nd generation anti-androgen therapy (i.e
Enzalutamide, Abiraterone, etc.),or chemotherapy given as part of the treatment of
prostate cancer.
- The patient should not have direct evidence of regional or distant metastases after
appropriate staging studies, including no distant metastases (M0) on bone scan within
90 days of study enrollment. Equivocal bone scan findings are allowed if plain films
are negative for metastasis. PET or PSMA scans can be performed instead of a bone
scan.
- Patients diagnosed with invasive malignancy are not eligible (except non-melanomatous
skin cancer) unless disease free for a minimum of 3 years (e.g., oral cavity).
- Patients diagnosed with severe, active co-morbidity, defined as follows are not
eligible:
- Unstable angina and/or congestive heart failure requiring hospitalization within the
last 6 months.
- Transmural myocardial infarction within the last 6 months.
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of
registration.
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days before
registration.
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note,
however, that laboratory tests for liver function and coagulation parameters are not
required for entry into this protocol.
- Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note,
however, that HIV testing is not required for entry into this protocol. The need to
exclude patients with AIDS from this protocol is necessary because the treatments
involved in this protocol may be significantly immunosuppressive. Protocol-specific
requirements may also exclude immuno-compromised patients.
- Patients with history of inflammatory colitis (including Crohn's Disease and
Ulcerative colitis), active lupus, and scleroderma or active collagen vascular disease
are not eligible.
- Patients should not have undergone previous transurethral resection of the prostate
(TURP) within 1 year.
- Patients with history of inflammatory colitis (including Crohn's Disease and
Ulcerative colitis) are not eligible.
- Patients should not have a history of significant psychiatric illness.
- Patients may have used prior hormonal therapy, but it should be limited to no more
than 9 months of therapy prior to enrollment.
