*Check for eligibility to DCP-001*

-Histologically confirmed ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal carcinoma
-Stage II, III, or IV disease
-No prior histological diagnosis of or treatment for clinical stage I epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal carcinoma
-Patients must have completed all primary chemotherapy and consolidation therapy (if administered) at least 6 weeks, and no more than 4 months, prior to enrollment and must be in complete remission
-Patients must have achieved a documented complete response to treatment based on normal CA-125 and CT scan
-GOG performance status 0-2
-Willing to provide names and appropriate telephone contact information and to be contacted periodically via telephone by Arizona Diet, Behavior and Quality of Life Shared Service staff for completion of individualized lifestyle intervention counseling
-Body Mass Index must be greater than 20 kg/m^2
- No patients enrolled in a weight-loss program or who are taking weight-loss medications or dietary supplements and are unwilling to discontinuation
-No other chronic disease that would preclude randomization into a lifestyle intervention trial including, but not limited to, any of the following:  Recent myocardial infarction or unstable angina (within the past 6 months), chronic hepatitis, rheumatoid disease, renal or hepatic disease or dysfunction, diabetics receiving insulin, other clinical condition limiting ability to walk (e.g., recent leg fracture, significant osteoarthritis, related orthopedic conditions, or degenerative neurological conditions)
-No vegans 
-No ongoing medically prescribed diet or physical activity regimen that has lasted for 6 months or longer
-Patients must not have a serious psychiatric illness (e.g., lifetime bipolar disorder, schizophrenia or other psychosis, serious personality disorder, severe major depressive disorder, recent suicide attempt, or psychiatric hospitalization (previous 12 months) 

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

**QOL substudy closed to accrual**

***Special Regs***See Section 5.0 REGISTRATION PROCEDURES.***

1. Adenocarcinoma of the prostate treated primarily with radical prostatectomy, pathologically proven to be lymph node negative by pelvic lymphadenectomy (N0) or lymph node status pathologically unknown (undissected pelvic lymph nodes [Nx]), i.e. lymph node dissection is not required;

Any type of radical prostatectomy will be permitted, including retropubic, perineal, laparoscopic or robotically assisted. If performed, the number of lymph nodes removed per side of the pelvis and the extent of the pelvic lymph node dissection (obturator vs. extended lymph node dissection) should be noted.

2. A post-radical prostatectomy entry PSA of ¡Ý 0.2 and < 2.0 ng/mL at least 6 weeks after prostatectomy and within 30 days of registration;

3. One of the following pathologic classifications:

T3N0/Nx disease; or

T2N0/Nx disease with positive prostatectomy margin and/or positive prostatic fossa or urethral-vesical anastomosis biopsies;

4. Prostatectomy Gleason score of 8 or less;

5. PSA Doubling Time (PSADT) of > 6 months prior to registration; PSA Doubling Time (PSADT) should be calculated via the Calculation of PSA Doubling Time page on the RTOG web site http://www.rtog.org/psadt.html. Review the instructions for calculating the PSADT located at the top of this page, and then select ¡°Retrieve PSADT value¡± at the bottom center of the page;

6. Zubrod Performance Status of 0-1;

7. Age >= 18;

8. A digital rectal exam within 30 days prior to registration

9. No distant metastases, based upon the following minimum diagnostic workup:

History/physical examination within 8 weeks prior to registration;

A CT scan (with contrast if renal function is acceptable) or MRI of the abdomen and pelvis within 90 days prior to registration;

Bone scan within 90 days prior to registration; if the bone scan is suspicious, a plain x-ray and/or MRI must be obtained to rule out metastasis.

10. Adequate bone marrow function, within 90 days prior to registration, defined as follows:

?? Platelets >= 100,000 cells/mm3 based upon CBC;

?? Hemoglobin >= 12.0 g/dl based upon CBC (Note: The use of transfusion or other

intervention to achieve Hgb >= 12.0 g/dl is acceptable).

11. AST or ALT < 2 x the upper limit of normal within 90 days prior to registration;

12. Serum total testosterone within 90 days prior to registration;

13. Patients must sign a study-specific informed consent prior to study entry.



Conditions for Patient Ineligibility

1. A palpable prostatic fossa abnormality/mass suggestive of recurrence, unless shown by biopsy under ultrasound guidance not to contain cancer;

2. N1 patients are ineligible, as are those with pelvic lymph node enlargement >= 1.5 cm in greatest dimension by CT scan or MRI of the pelvis, unless the enlarged lymph node is sampled and is negative;

3. Androgen deprivation therapy started prior to prostatectomy for > 6 months duration;

4. Androgen deprivation therapy started after prostatectomy and prior to registration;

5. Prior pelvic radiotherapy;

6. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 5 years (for example, carcinoma in situ of the oral cavity is permissible);

7. PSA doubling time of <= 6 months;

8. Severe, active co-morbidity, defined as follows:

History of inflammatory bowel disease;

History of hepatitis B or C; Blood tests are not required to determine if the patient has had hepatitis B or C, unless the patient reports a history of it.

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 at the time of registration;

Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; AST or ALT are required (see Section 3.1.11); note, however, that laboratory tests for 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 result in increased toxicity and immunosuppression.

8. Prior allergic reaction to the study drug(s) involved in this protocol.

 *Credentialing required. Please check your site's credentialing status.*
CURRENT SITES CREDENTIALED:
Genesys Hurley, Livonia, Macomb, Oakland, Saginaw, Sparrow, St. Alphonsus, St. John, SJMH

-Histologically confirmed adenocarcinoma of the prostate diagnosed within the past 6 months and at intermediate-risk for recurrence by meeting at least one of the following criteria:
--Gleason score 7
--PSA > 10 but less than or equal to 20
--clinical stage T2b-T2c 
-No patients with all 3 intermediate-risk factors who also have greater than or equal to 50% of the number of their biopsy cores positive for cancer
-Clinically negative LNs as established by imaging, nodal sampling or dissection within 60d prior to registration
-No evidence of bone mets on bone scan
-Zubrod performance status must be 0-1
-No prior radical surgery (prostatectomy), high-intensity focused ultrasound, or cryosurgery for prostate cancer
-No prior hormonal therapy, such as LHRH agonists (e.g., goserelin, leuprolide), antiandrogens (e.g., flutamide, bicalutamide), estrogens (e.g., DES), or bilateral orchiectomy
-No finasteride within past 30 days (90 days for dutasteride)
-No prior or concurrent cytotoxic chemotherapy for prostate cancer
-No prior radiotherapy (RT), including brachytherapy, to the region of the study cancer that would result in overlap of RT fields

 *Credentialing required. Please check your site's credentialing status.*
CURRENT SITES CREDENTIALED:
Livonia, Macomb, Oakland, Oakwood, Saginaw, St. Alphonsus, St. John, SJMH 
-Histologically confirmed squamous cell carcinoma (including variants, such as verrucous carcinoma, spindle cell carcinoma, or carcinoma not otherwise specified) of the head and neck, including the following subtypes: Oral cavity; oropharynx; larynx
-Clinical stage T1, N1-2, M0 OR T2-3, N0-2, M0 disease based on the following diagnostic workup within the past 8 weeks
-Must have undergone gross total resection of the primary tumor with curative intent within the past 7 weeks with surgical pathology demonstrating one or more of the following criteria for "intermediate" risk of recurrence:
--perineural invasion
--lymphovascular invasion
--single lymph node greater than 3 cm or greater than or equal to 2 lymph nodes (all < 6 cm) (no extracapsular extension)
--close margin(s) of resection, defined as cancer extending to within 5 mm of a surgical margin
--T3 or microscopic T4a primary tumor
--T2 oral cavity cancer with > 5 mm depth of invasion 
-No positive margin(s) (defined as tumor present at the cut or inked edge of the tumor), nodal extracapsular extension, and/or gross residual disease after surgery
-Zubrod performance status must be 0-1
-No prior systemic chemotherapy or anti-EGF therapy for this cancer but prior chemotherapy or anti-EGF therapy for a different cancer is allowed
-No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields  

**QOL portion of study closed to accrual effective 02/28/13**

**Video Fluoroscopic Swallow Study (VFSS) must be done at baseline. Nurse can do second swallow test.**

****SPECIAL REGS REQUIRED PRIOR TO PATIENT ENTRY ****

See Section 5.0

FOR THIS STUDY, IMRT IS MANDATORY.

IGRT credentialing is MANDATORY when using PTV margins < 5 mm

The institution or investigator must complete a new Facility Questionnaire specifically for this

study, and send it to RTOG for review prior to entering any cases, and/or set up an SFTP account

for digital data submission, both of which are available on the Image-Guided Center (ITC) web

site at http://atc.wustl.edu.

Section 5.5.1 

Prior to registration of the institution’s first case, participating institutions must register into the

CASI system for access to computer software and hardware (iPAD) for administration of the

following: 1) the mandatory smoking survey for all participants; 2) the optional QOL Patient-

Reported Outcomes assessments; and 3) the optional head and neck cancer risk factor survey.

3.1 Conditions for Patient Eligibility

3.1.1

(including the histological variants papillary squamous cell carcinoma and basaloid squamous

cell carcinoma) of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls);

Note

smears are not. Patients with a diagnosis based upon cytopathology alone may require biopsy

of the primary tumor for eligibility determination.

3.1.2 Patients must be positive for p16, determined by the OSU Innovation Center CLIA lab

prior to Step 2 registration (randomization)

3.1.3

or at nodal stations. Tonsillectomy or local excision of the primary without removal of nodal

disease is permitted, as is excision removing gross nodal disease but with intact primary site.

Limited neck dissections retrieving

nodal excisions. Fine needle aspirations of the neck are insufficient due to limited tissue for

retrospective central review. Biopsy specimens from the primary or nodes measuring at least 3-

5 mm are required.

3.1.4

distant metastases, based upon the following minimum diagnostic workup:

3.1.4.1

within 8 weeks prior to registration;

3.1.4.2

and/or fiberoptic and/or direct procedure) within 8 weeks prior to registration;

3.1.4.3

MRI of the neck and a chest CT scan (with or without contrast); or a CT scan of neck and a

PET/CT of neck and chest within 8 weeks prior to registration; Note: A CT scan of neck

and/or a PET/CT performed for radiation planning may serve as both staging and planning

tools.

3.1.5

3.1.6

3.1.7

marrow function, defined as follows:

3.1.7.1

3.1.7.2

3.1.7.3

8.0 g/dl is acceptable.

3.1.8

3.1.8.1

3.1.8.2

3.1.9

3.1.9.1

=

estimated by Cockcroft-Gault formula:

CCr male = [(140 – age) x (wt in kg)]

[(Serum Cr mg/dl) x (72)]

CCr female = 0.85 x (CrCl male)

3.1.10 Patients must provide their smoking history (for stratification) via the computer-assisted

self interview (CASI) head and neck risk factor survey tool.

3.1.11

potential;

3.1.12

means of birth control throughout their participation in the treatment phase of the study and

until at least 60 days following the last study treatment.

**SJMH is the only site participating in this study.

Eligibility Criteria:

4.1.1 Patient meets all eligibility criteria for treatment of the tumors with the agents listed in Table 1 and has agreed to provide tissue and blood samples for this study.

• Targeted therapy maybe as a singular/monotherapy or in combination with any FDA-approved chemotherapies.

• Patient’s primary or recurrent disease is targeted-treatment naïve or will be treated with a targeted therapy listed in Table 1 different from any previously-received targeted therapy or combination therapy as standard of care.

4.1.2 ECOG Performance Status (PS) 0 or 1. Patients with a PS of 2 may be enrolled only at the discretion of the treating physician and radiologist.

4.1.3 Age 18 or older.

4.1.4 Have an advanced malignancy being treated with one of the agents listed in Table 1. Advanced cancer is cancer that is unlikely to be cured or controlled with treatment. The cancer may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body. Treatment may be given to help shrink the tumor, slow the growth of cancer cells, or relieve symptoms. Patients may be undergoing first or subsequent lines of therapy. In the case where an agent not listed in Table 1 is newly approved for one of the listed tumors, patients undergoing therapy with it will be able to enroll at discretion of the PI. This is to avoid any lag between FDA approval of a previously investigational agent and protocol modifications/updates.

4.1.5 Have an advanced malignancy that meets one of the following criteria:

• Patients must have tumor amenable to image guided or direct vision biopsy and be willing and able to undergo a tumor biopsy for molecular profiling. The biopsy must not be associated with a significant risk of severe or major complications or death. In particular, endoscopic, open or laparoscopic surgical procedures are not to be performed to provide research specimens. However, research specimens may be provided if the patient needs to undergo such procedures for clinical reasons.

Severe or major complications are considered to be those

o Requiring therapy, minor hospitalization (more than overnight but <48 h)

o Requiring major therapy; unplanned increase in level of care, prolonged hospitalization >48 h

o Resulting in permanent adverse sequelae

o Resulting in death

• Patient will be undergoing a procedure due to medical necessity during which the tissue may be collected. The following tumors may be collected only under the conditions specified and not for the sole purpose of the clinical trial:

o Brain biopsies: ONLY if the patient has medical necessity for craniotomy for clinical care.

o Mediastinal, laparoscopic, gastrointestinal, or bronchial endoscopic biopsies: ONLY to be obtained incidentally to a clinically necessary procedure.

4.2.1 Uncontrolled intercurrent illness that in the physician’s assessment would pose undue risk for biopsy.

4.2.2 Patients currently enrolled or planning to be co-enrolled (while participating on the 10231 study) on a therapeutically interventional clinical trial aimed to treat the current malignancy.

4.2.3 If the patient is on chronic anticoagulation treatment, they must be able and willing to have this treatment discontinued for the biopsy. Discontinuation procedures will be those of the treating site.

**SJMH, Livonia, and SJMO will be the only site participating**

4.1.1 Patient diagnosed with Stage IV colorectal cancer, Stage III/IV non-small cell or small cell lung cancer, metastatic castration-resistant prostate cancer, Stage IV gastroesophageal cancer, Stage III/IV melanoma, newly diagnosed acute myeloid leukemia or treatment refractory multiple myeloma, is undergoing standard of care therapy per NCCN guidelines (https://www.nccn.org/professionals/physician_gls/default.aspx) and has consented to provide longitudinal biospecimens.

4.1.2 Patients with ECOG Performance Status (PS) 0 or 1 may be enrolled retrospectively (i.e.

at time of progression) if archival material is submitted that contains the cancer type for

which the participant is enrolled and that was collected up to 5 years prior to initiation of

a therapy listed in Table 1, assuming that no intervening molecular targeted or

immunotherapies were administered (Archival Material Collection; Section

7.2.1).Patients with a PS of 2 may be enrolled only at the discretion of the treating

physician and radiologist.

4.1.3 Age 13 or older and any gender may be enrolled.

4.1.4 Patients must have tumor amenable to image guided or direct vision biopsy and be

willing and able to undergo a tumor biopsy for molecular profiling

(https://www.ncbi.nlm.nih.gov/pubmed/?term=30285529). The biopsy must not be associated with a significant risk of severe or major complications or death. In particular, endoscopic, open or laparoscopic surgical procedures are not to be performed to provide research biospecimens. However, research biospecimens may be provided if the patient needs to undergo such procedures for clinical reasons. Severe or major complications are considered to be those:

• Requiring therapy, minor hospitalization (more than overnight but <48 h).
• Requiring major therapy; unplanned increase in level of care, prolonged hospitalization >48 h.
• Resulting in permanent adverse sequelae.
• Resulting in death.

The following tumors may be collected only when patients will be undergoing a procedure due to medical necessity during which the tissue may be collected and not for the sole purpose of the clinical study:

• Brain biopsies: ONLY if the patient has medical necessity for craniotomy for clinical care.
• Mediastinal, laparoscopic, gastrointestinal, or bronchial endoscopic biopsies: ONLY to be obtained incidentally to a clinically necessary procedure.

4.1.5 Study participants with CRC, PCA, GEC and MEL may contribute samples for PDM

development if they meet specific PDMR eligibility criteria (Appendix F).

4.1.6 Study participants with LCA and treated with standard of care EGFR, ALK, PD-1 and

PD-L1 antagonists listed in Table 1 and MML may contribute samples directly to

Moonshot investigators if they meet specific DRSN eligibility criteria (Appendix F).

4.1.7 To ensure that individuals who experience diminished decision making capacity during

the course of their cancer treatment are eligible, consent may be provided by a Legally

Authorized Representative (LAR) in accordance with 45 CFR 46.102(i). This protocol

is minimal risk.