**ePRO training required prior to first patient enrollment.** 

CREDENTIALING REQUIRED. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED: SJMH (Ann Arbor, Brighton), Saginaw

***SJMH: Patients randomized to the SRS arm can ONLY be treated in Ann Arbor.*** 

Eligibility Criteria:

*A patient cannot be considered eligible for this study unless ALL of the following conditions are met.

- Pathologically (histologically or cytologically) proven diagnosis of small cell lung cancer within 5 years of registration. If the original histologic proof of malignancy is greater than 5 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic or brain metastasis);

o Patients with de novo or recurrent small cell lung cancer are permitted. 

Ten or fewer brain metastases ≤3cm in largest diameter and outside a 5-mm margin around either hippocampus must be visible on contrast-enhanced MRI performed ≤21 days prior to study entry.

o Brain metastases can be diagnosed synchronous to the initial diagnosis of small cell lung cancer or metachronous to the initial diagnosis and management of small cell lung cancer.

o The total tumor volume must be 30 cm3 or less. Lesion volume will be approximated by measuring the lesion’s three perpendicular diameters on contrast\u0002enhanced, T1-weighted MRI and the product of those diameters will be divided by 2 to estimate the lesion volume (e.g. xyz/2). Alternatively, direct volumetric measurements via slice by slice contouring on a treatment planning software package can be used to calculate the total tumor volume.

o Brain metastases must be diagnosed on MRI, which will include the following elements:

REQUIRED MRI ELEMENTS

• Post gadolinium contrast-enhanced T1-weighted three-dimensional (3D) spoiled gradient (SPGR). Acceptable 3D SPGR sequences include magnetization\u0002prepared 3D gradient recalled echo (GRE) rapid gradient echo (MP-RAGE), turbo field echo (TFE) MRI, BRAVO (Brain Volume Imaging) or 3D Fast FE (field echo). The T1-weighted 3D scan should use the smallest possible axial slice thickness, not to exceed 1.5 mm.

• Pre-contrast T1 weighted imaging (3D imaging sequence strongly encouraged).

• A minimum of one axial T2 FLAIR (preferred) or T2 sequence is required. This can be acquired as a 2D or 3D image. If 2D, the images should be obtained in the axial plane. 

ADDITIONAL RECOMMENDATIONS

• Recommendation is that an axial T2 FLAIR (preferred) sequence be performed instead of a T2 sequence.

• Recommendation is that that pre-contrast 3D T1 be performed with the same parameters as the post-contrast 3D T1.

• Recommendation is that imaging be performed on a 3 Tesla (3T) MRI.

• Recommendation is that the study participants be scanned on the same MRI instrument at each time point.

• Recommendation is that if additional sequences are obtained, these should meet the criteria outlined in Kaufmann et al., 2020.

• If additional sequences are obtained, total imaging time should not exceed 60 minutes. See Appendix IV for a summary of key imaging requirements, and contact the Principal Investigators and Imaging Co-Chairs for further information or assistance if needed.

- History/physical examination within 28 days prior to registration;

- Age ≥ 18;  

Karnofsky Performance Status of ≥70 within 28 days prior to registration;

-Adequate renal function within 28 days prior to registration defined as follows:

• Creatinine clearance ≥30 ml/min

- Following the diagnosis of brain metastases, patients can initiate and treat with systemic (chemotherapy and/or immunotherapy) before enrollment only if their brain metastases are asymptomatic and not located in eloquent locations (e.g., brainstem, pre-/post-central gyrus, visual cortex). However, within 21 days prior to enrollment, brain MRI must be repeated to confirm eligibility.

o Patients with symptomatic brain metastases and/or brain metastases in eloquent locations (e.g., brainstem, pre-/post-central gyrus, visual cortex) are eligible for enrollment on the trial; however, the specific treatment approach of starting with systemic therapy alone and delaying brain radiation is not recommended for these patients.

- Concurrent immunotherapy with brain radiation (SRS or HA-WBRT) is permitted.

- Negative urine or serum pregnancy test (in women of childbearing potential) within 14 days prior to registration. Women of childbearing potential and men who are sexually active must use contraception while on study.

- Patients may have had prior intracranial surgical resection. Patients must have completed prior intracranial surgical resection at least 14 days prior to registration.

- Because neurocognitive testing is the primary goal of this study, patients must be proficient in English or French Canadian.

- The patient must provide study-specific informed consent prior to study entry.

• Patients with impaired decision-making capacity are not permitted on study.  

Eligibility Criteria Prior to Step 2 Registration

- The following baseline neurocognitive tests must be completed within 21 days prior to Step 2 registration: HVLT-R, TMT, and COWA. The neurocognitive tests will be uploaded into RAVE for evaluation by Dr. Wefel. Once the upload is complete, within 1 business day a notification will be sent via email to the RA to proceed to Step 2. NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step 1 registration.

- Ineligibility Criteria Patients with any of the following conditions are NOT eligible for this study.

- Planned infusion of cytotoxic chemotherapy on the same day as SRS or HA-WBRT treatment. Patients may have had prior chemotherapy. As noted in 3.1.8, concurrent immunotherapy is permitted.

- Prior allergic reaction to memantine.

- Intractable seizures while on adequate anticonvulsant therapy; more than 1 seizure per month for the past 2 months.

- Patients with definitive leptomeningeal metastases.

- Known history of demyelinating disease such as multiple sclerosis

- Contraindication to MR imaging such as implanted metal devices that are MRI\u0002incompatible, allergy to MRI contrast that cannot be adequately addressed with pre- contrast medications, or foreign bodies that preclude MRI imaging. (Questions regarding MRI compatibility of implanted objects should be reviewed with the Radiology Department performing the MRI).

- Current use of (other NMDA antagonists) amantadine, ketamine, or dextromethorphan

- Radiographic evidence of hydrocephalus or other architectural change of the ventricular system resulting in significant anatomic distortion of the hippocampus, including placement of external ventricular drain or ventriculoperitoneal shunt.

• Mild cases of hydrocephalus not resulting in significant anatomic distortion of the hippocampus are permitted

- Prior radiotherapy to the brain, including SRS, WBRT, or PCI 3.3.10 Severe, active co-morbidity defined as follows:

• 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 acute respiratory illness precluding study therapy at the time of registration

• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

CREDENTIALING REQUIRED. Please check your site's credentialing status.

CURRENT SITES CREDENTIALED: Trinity Health (Ann Arbor, Canton, Brighton, Chelsea), Livonia, Lehigh Valley

Eligibility Criteria:

3.2.1 Definition of Disease

• Patients with polymetastatic cancer defined as more than 5 sites of radiographically evident systemic metastatic disease (excluding intracranial disease).

• “High-risk” asymptomatic bone metastasis(es) (BPI score of < 5 on the “maximum” pain item) defined as fulfilling at least one of the following four high-risk criteria:

1. Bulky site of disease in bone (≥ 2 cm);

2. Disease involving the hip (acetabulum, femoral head, femoral neck), shoulder (acromion, glenoid, humeral head), or sacroiliac joints;

3. Disease in long bones occupying up to 2/3 of the cortical thickness (humerus, radius, ulna, clavicle, femur, tibia, fibula, metacarpals, phalanges); and/or

4. Disease in junctional spine (C7-T1, T12-L1, L5-S1) and/or disease with posterolateral element (pedicles and/or facet joints) involvement.

NOTES: Patients may have up to 3 individual high-risk bone metastases enrolled in the study. Sternum, rib, and scapula are defined as flat bones so lesions in these locations would only be included if bulky (per high-risk criteria #1).

• Patients with any solid tumor type (excluding multiple myeloma).

• Patients must have systemic disease evaluation through standard of care diagnostic imaging, including either CT chest/abdomen/pelvis or body PET/CT, with radiology report available. Brain Metastasis criteria

• Patients with treated brain metastases and no known leptomeningeal disease are eligible if these lesions have been treated prior to enrollment.

3.2.2 Age ≥ 18

3.2.3 Performance Status: ECOG 0-2 or KPS ≥ 60 3.2.4 Prior Treatment No previous radiotherapy to the intended enrolled sites of disease. 

3.2.5 Comorbid Conditions

• No epidural spinal cord compression (ESCC) ≥ Grade 1c (defined as deformation of the thecal sac with spinal cord abutment) at the enrolled bone metastasis(es).

• No prior fracture at the enrolled bone metastasis(es).  

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST** 

CREDENTIALING REQUIRED. Please check your site's credentialing status.

CURRENT SITES CREDENTIALED: TH, ,Oakland, MyMichigan, Saint Alphonsus

Eligibility Criteria:

3.2.1 The participant must provide study-specific informed consent prior to Registration and, for participants treated in the U.S., authorization permitting release of personal health information.

3.2.2 The participant must have been ≥ 18 or <51 years of age at the time of breast cancer diagnosis. 3.2.3 The participant must have a first-time diagnosis of non-metastatic breast cancer which is Stage 0, I, II, or III.

3.2.4 The participant must have a score of ≥ 5 and ≤ 14 on the Patient Health Questionnaire-8 item (PHQ-8).

3.2.5 Participants must have completed all primary breast cancer treatments at least 6 months prior to and no more than 5 years prior to registration. Note: Primary treatments include surgery, radiation therapy, adjuvant chemotherapy, and targeted therapies (e.g., PARP inhibitors, CDK4/6 inhibitors, TDM-1, pertuzumab, or immunotherapy). Participants may still be taking adjuvant therapy with trastuzumab or adjuvant endocrine therapy or completing minor reconstructive surgery.

3.2.6 The participant must be able to understand, speak, read, and write in English or Spanish.

3.2.7 Participant must be willing to participate in a 6-week program to receive training in mindfulness. 3.2.8 Participant must be able to use a smartphone, tablet, or other digital device.

3.2.9 Sex assigned at birth must be female. 

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST** 

*DTL Required- Physicians must sign toxicity grid
Current sites credentialed: SJMH, Sparrow, Livonia, Lehigh, Saginaw, Oakland

-ECOG Performance Status of 0, 1 or 2
-Diagnosis of metastatic adenocarcinoma of colon or rectum without previous chemotherapy or any other systemic therapy for metastatic colorectal cancer.
-Tumor determined to be mismatch-repair deficient (dMMR) by CLIA-certified immunohistochemical (IHC) assay with a panel of all four IHC markers, including MLH1, MSH2, PMS2, and MSH6.
-An adequate amount of archived tumor tissue, either from primary colorectal cancer site or metastatic lesions, for central confirmation of dMMR status:

-Either whole or part of the FFPE block containing tumor tissue; or

-At least 8 unstained slides containing tumor sections

Eligibility Criteria:

- The patient must have signed and dated an IRB-approved consent form that conforms to federal and institutional guidelines.

- Age = 18 years at diagnosis.

- ECOG Performance Status of 0 or 1 (see Appendix A).

- Histologically/pathologically confirmed stage IIA adenocarcinoma of the colon (T3, N0, M0) with at least 12 lymph nodes examined at the time of surgical resection.

- Appropriate for active surveillance (i.e., no adjuvant chemotherapy) at the discretion of and as documented by the evaluating oncologist based on current practice patterns.

- The distal extent of the tumor must be =12 cm from the anal verge on pre-surgical endoscopy (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation). If the patient did not undergo a pre-surgical endoscopy, then the distal extent of the tumor must be =12 cm from the anal verge as determined by surgical examination or pre-operative imaging.

- The patient must have had an en bloc complete gross resection of tumor (curative resection) as definitive surgical cancer treatment within 14 to 60 days of study randomization. Patients who have had a two-stage surgical procedure to first provide a decompressive colostomy and then, in a later procedure, to have the definitive surgical resection, are eligible.

- Availability and provision of adequate surgical tumor tissue for molecular diagnostics and confirmatory profiling.

-Adequate hematologic function within 28 days before randomization defined as follows:

• Absolute neutrophil count (ANC) must be = 1200/mm3;

• Platelet count must be = 100,000/mm3; and

• Hemoglobin must be = 9 g/dL.

- Adequate hepatic function within 28 days before randomization defined as follows:

• total bilirubin must be = ULN (upper limit of normal) for the lab unless the patient has a chronic grade 1 bilirubin elevation due to Gilbert’s disease or similar syndrome involving slow conjugation of bilirubin; and

• alkaline phosphatase must be 2.5 x ULN for the lab; and

• AST and ALT must be 1.5 x ULN for the lab.

- Adequate renal function within 28 days before randomization defined as serum creatinine = 1.5 x ULN for the lab or measured or calculated creatinine clearance = 50 mL/min using the Cockroft-Gault formula for patients with creatinine levels > 1.5 x ULN for the lab.

- Pregnancy test (urine or serum according to institutional standard) done within 14 days before randomization must be negative (for women of childbearing potential only).

- Patients receiving a coumarin-derivative anticoagulant must agree to weekly monitoring of INR if they are randomized to Arm 2 and receive capecitabine.

CREDENTIALING REQUIRED. Please check your site's credentialing status.

CURRENT SITES CREDENTIALED:  SJMH (AA, Brighton, Canton, Chelsea), Livonia, Genesys, St. John, Macomb, Saginaw, LVHN, Sparrow, SJMO, Holy Cross

Eligibility Criteria: 

Patient Entry and Randomization

The following sections outline procedures for Study Entry and Randomization.

Step 1: Study Entry and ctDNA assay testing.

• The authorized site staff must obtain signed informed consent from the potential patient before any study specific procedures are performed.

• The authorized site staff must determine patient eligibility by completing the assessments on Table 1 that are required prior to study entry. See Sections 3.2 and 3.3.

• Step 1 Entry in OPEN: Patients will be assigned a unique patient identifier which will be used to identify the blood and tumor samples to be sent for central Signatera? ctDNA testing for patients who have not had ctDNA testing performed using the Signatera? assay as routine care outside the study and for those patients who already have had a ctDNA status performed using the Signatera? assay as routine care outside of the study, the eCRFs in Medidata RAVE, and any other trial-related communications.

Step 2: Randomization

• Following ctDNA assay testing, the authorized site staff will randomize the patient using OPEN. For the patients who had their ctDNA status checked with the Signatera? assay as routine care outside of the study, the ctDNA test result from the central testing will be the result used to place the patients in Cohort A or Cohort B. When the result of the central ctDNA testing is not the same as the result of the Signatera? assay done as routine care outside of the study, the patient/physician may choose not to proceed with participation in the study.

• OPEN will randomly assign treatment by cohort (ctDNA-ve or ctDNA+ve).

Second Randomization (Cohort A-Arm 2 patients who convert to ctDNA +ve)

• Cohort A-Arm 2 patients who develop a positive ctDNA assay during serial monitoring will transition to the ctDNA+ ve cohort (Cohort B) and undergo a second randomization to Arm 3 or Arm 4 treatment.

• The authorized site staff must determine patient eligibility (see Section 3.4).

• Patients must reaffirm their willingness to be enrolled in Cohort B and randomized to Arm 3 or 4 after review of the current consent form and signing a reaffirmation form.

• OPEN will randomly assign patient to Arm 3 or Arm 4.

 Eligibility Criteria

A patient cannot be considered eligible for this study unless ALL of the following conditions are met.

- The patient must have signed and dated an IRB-approved consent form that conforms to federal and institutional guidelines.

- The patient must be ≥ 18 years old.

- The patient must have an ECOG performance status of 0 or 1 (see Appendix A).

- Patients must have histologically/pathologically confirmed Stage IIIA or Stage IIIB colon adenocarcinoma (T1-3, N1/N1c) with R0 resection accordingly to AJCC 8th edition criteria. NOTE: Patients with pathologic stages II or IIIC colon adenocarcinoma with R0 resection who have a commercially obtained Signatera? ctDNA+ve assay result post-operatively meeting all timelines and eligibility requirements otherwise, are eligible for enrollment and inclusion in Cohort B.

- No radiographic evidence of overt metastatic disease within 28 days prior to study entry (CT with IV contrast or MRI imaging is acceptable and must include chest, abdomen, and pelvis).

- The distal extent of the tumor must be ≥ 12 cm from the anal verge on colonoscopy or above the peritoneal reflection as documented during surgery or on pathology specimen (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation).

- The patient must have had an en bloc complete gross resection of tumor (curative resection). Patients who have had a two-stage surgical procedure, to first provide a decompressive colostomy and then in a later procedure to have the definitive surgical resection, are eligible.

-The resected tumor specimen and a blood specimen from patients with Stage IIIA or Stage IIIB colon cancer must have central testing for ctDNA using the Signatera assay by Natera. NOTE: Patients with stage IIIA or IIIB colon cancer who otherwise meet eligibility criteria and have had ctDNA status checked with the Signatera? assay as routine care outside of the study, are allowed to be enrolled, and will be retested and placed in either Cohort A or Cohort B depending on the central ctDNA testing result. NOTE: Patients with stage II or IIIC colon cancer who otherwise meet eligibility criteria and have had ctDNA status checked with the Signatera? assay as routine care outside of the study AND have a ctDNA+ve result, are allowed to be enrolled. Patients will have central ctDNA testing, confirmed to be ctDNA+ve, and placed in Cohort B.

-Tumor must be documented as microsatellite stable or have intact mismatch repair proteins through CLIA-approved laboratory testing. Patients whose tumors are MSI-H or dMMR are excluded.

- The treating investigator must deem the patient a candidate for all potential agents used in this trial (5FU, LV, oxaliplatin and irinotecan).

- The interval between surgery (post-operative Day 7) and study entry must be no more than 60 days.

- Availability and provision of adequate surgical tumor tissue for molecular diagnostics and confirmatory profiling.

Adequate hematologic function within 28 days before study entry defined as follows:

• Absolute neutrophil count (ANC) must be ≥ 1500/mm3;

• Platelet count must be ≥ 100,000/mm3; and  

• Hemoglobin must be ≥ 9 g/dL. 3.2.14 Adequate hepatic function within 28 days before study entry defined as follows:

• total bilirubin must be ≤ ULN (upper limit of normal) for the lab and

• alkaline phosphatase must be < 2.5 x ULN for the lab; and

• AST and ALT must be < 2.5 x ULN for the lab. 3.2.15 Adequate renal function within 28 days before study entry defined as serum creatinine ≤ 1.5 x ULN for the lab or measured or calculated creatinine clearance ≥ 50 mL/min using the Cockroft\u0002Gault formula for patients with creatinine levels > 1.5 x ULN for the lab. For Women Creatinine Clearance (mL/min) = (140 – age) x weight (kg) x 0.85 72 x serum creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 – age) x weight (kg) 72 x serum creatinine (mg/dL)

- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

- Pregnancy test (urine or serum according to institutional standard) done within 14 days before study entry must be negative (for women of childbearing potential only).

- Patients receiving a coumarin-derivative anticoagulant must agree to weekly monitoring of INR if they are randomized to Arm 1 or Arm 3 and receive capecitabine.

Ineligibility Criteria

Patients with any of the following conditions are NOT eligible for this study.

- Colon cancer histology other than adenocarcinoma (i.e., neuroendocrine carcinoma, sarcoma, lymphoma, squamous cell carcinoma, etc.).

- Pathologic, clinical, or radiologic overt evidence of metastatic disease. This includes isolated, distant, or non-contiguous intra-abdominal metastases, even if resected.

- Tumor-related bowel perforation.

- History of prior invasive colon malignancy, regardless of disease-free interval.

- History of bone marrow or solid organ transplantation (regardless of current immunosuppressive therapy needs). Bone grafts, skin grafts, corneal transplants and organ/tissue donation are not exclusionary.

- Any prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy administered as treatment for colorectal cancer (e.g., primary colon adenocarcinomas for which treatment with neoadjuvant chemotherapy and/or radiation is warranted are not permitted).

- Other invasive malignancy within 5 years before study entry. Exceptions are colonic polyps, non-melanoma skin cancer or any carcinoma-in-situ.

- Synchronous primary rectal and/ or colon cancers.

- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. 

-Sensory or motor neuropathy ≥ grade 2, according to CTCAE v5.0.

- Blood transfusion within two weeks before collection of blood for central ctDNA testing.

- Active seizure disorder uncontrolled by medication.

- Active or chronic infection requiring systemic therapy.

- Known homozygous DPD (dihydropyrimidine dehydrogenase) deficiency.

- Patients known to have Gilbert's Syndrome or homozygosity for UGT1A1*28 polymorphism.

- Pregnancy or lactation at the time of study entry.

- Co-morbid illnesses or other concurrent disease that would make the patient inappropriate for entry into this study (i.e., unable to tolerate 6 months of combination chemotherapy or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens or prevent required follow-up).

- Eligibility Criteria for Cohort A Arm-2 patients on Second Randomization

- Patient must have developed a ctDNA +ve assay during serial monitoring.

- Patient's willingness to be re-randomized affirmed.

- The patient must continue to have an ECOG performance status of 0 or 1 (see Appendix A).

- No radiographic evidence of overt metastatic disease.

- Pregnancy test (urine or serum according to institutional standard) done within 14 days before second randomization must be negative (for women of childbearing potential only).

- Adequate hematologic function within 28 days before second randomization defined as follows:

• Absolute neutrophil count (ANC) must be ≥ 1500/mm3;

• Platelet count must be ≥ 100,000/mm3; and

• Hemoglobin must be ≥ 9 g/dL.

- Adequate hepatic function within 28 days before second randomization defined as follows:

• total bilirubin must be ≤ ULN (upper limit of normal) for the lab and

• alkaline phosphatase must be < 2.5 x ULN for the lab; and

• AST and ALT must be < 2.5 x ULN for the lab.

- Adequate renal function within 28 days before second randomization defined as serum creatinine ≤ 1.5 x ULN for the lab or measured or calculated creatinine clearance ≥ 50 mL/min using the Cockroft-Gault formula for patients with creatinine levels > 1.5 x ULN for the lab. 

-Ineligibility Criteria for Cohort A Arm-2 patients on Second Randomization

- Pregnancy or lactation at the time of second randomization.

- No longer a candidate for systemic chemotherapy (FOLFOX, CAPOX, and mFOLFIRINOX) in the opinion of the treating investigator.  

CREDENTIALING REQUIRED. Please check your site's credentialing status.

CURRENT SITES CREDENTIALED: Trinity Health (Brighton, Canton, Ann Arbor, Chelsea, Livonia, Sparrow, MyMichigan

Eligibility Criteria:

 3.3 BASELINE PRE- ENTRY CHEMOTHERAPY REQUIREMENTS

3.3.1 Documentation of Disease Pathologically (histologically or cytologically) proven diagnosis of pancreatic ductal adenocarcinoma.

3.3.2 Definition of Disease

• Locally advanced unresectable disease (as defined per the National Comprehensive Cancer Network (NCCN) guidelines and institutional tumor board review).

• Patients must have baseline pre-chemotherapy scans for staging. Options include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen performed prior to enrollment.

3.3.3 Age ? 18 years

3.3.4 Performance Status ECOG 0-2

3.3.5 Required Initial Laboratory Values Baseline CA19-9 with a normal bilirubin level (defined as ? 1.2 mg/dl). AST and ALT ? 3x ULN.

3.4 POST PRE-ENTRY CHEMOTHERAPY REQUIREMENTS

3.4.1 Required Laboratory Values

• If baseline CA19-9 is elevated (defined as >37 u/mL) the post-pre-entry chemotherapy CA19-9 must be less than 37 u/mL or a 50% decline from pre-chemotherapy level with absolute value less than 100u/mL

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST** 

*Credentialing required. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED:
SJMH, Livonia,Sparrow, SJMO, Saginaw

-Patients post-prostatectomy with baseline Gleason ? 7 (per prostatectomy pathology)
-Baseline PSA nadir ? 0.2 ng/ml
-Pathologically proven diagnosis of adenocarcinoma of the prostate. Prostatectomy must have been performed within 365 days (1 year) prior to Step 1
-Prior androgen deprivation therapy (LHRH agonist and/or non-steroidal anti-androgen) is allowed if discontinued at least 90 days prior to study enrollment and given for ? 90 days duration.
-Pathologically lymph node negative by pelvic lymphadenectomy (pN0) or lymph node status pathologically unknown
-Any pT-stage is eligible.
-ECOG PS must be 0-1
-Must NOT have clinical or radiologic evidence of metatstatic disease
-Must not have prior RT that would result in overlap of fields
-Must not have prior systemic chemotherapy for this cancer
-Prior whole gland ablative therapy is not allowed

CREDENTIALING REQUIRED. *Please check your site's credentialing status.
CURRENT SITES CREDENTIALED:
Genesys Hurley, Livonia, SJMH, Sparrow, SJMO

-Adenocarcinoma of the prostate treated primarily with radical prostatectomy
-pathologic T-classifications: pT2 or pT3. Patients with positive surgical margins are eligible
-pathologic N-classifications: pN0, pNX.
-No clinical evidence of regional lymph node metastasis.
-A post-radical prostatectomy study entry PSA =45 days after prostatectomy and within 30 days prior to Step 1, 2.0 ng/mL.
-No evidence of a local recurrence in the prostate fossa based on a digital rectal examination (DRE)
-No evidence of bone metastases
-Zubrod Performance Status 0-1
-Must not have post-prostatectomy PSA nadir = 0.2 ng/mL AND Gleason = 7
-Must not be pT2 with a negative surgical margin and PSA 0.1 ng/mL
-Must not have had androgen deprivation therapy started prior to prostatectomy for > 6 months
-Must not have had androgen deprivation therapy started after prostatectomy for > 6 weeks
-Must not have had neoadjuvant chemotherapy before or after prostatectomy.
-Must not have had prior RT, including brachytherapy, to the region of the study cancer that would result in overlap of RT volumes.