Summaries - Symptom Management/Cancer Prevention Symptom Management/Cancer Prevention Protocols RTOG 0517 Number: 0517 Title: Randomized Phase III Trial to Evaluate Radiopharmaceuticals and Zoledronic Acid in the Palliation of Osteoblastic Metastases from Lung, Breast, and Prostate Cancer Eligibility: Histologically or cytologically proven diagnosis of solid tumor malignancy of lung, breast, or prostate prior to registration; appropriate diagnosis for protocol entry, based upon the diagnostic workup specified in the protocol; > 18 years of age; Zubrod performance status 0-2 for patients with breast or prostate primaries; Zubrod performance status 0-1 for patients with lung primaries; adequate bone marrow function as defined in the protocol; serum creatinine < 3 mg/dL (265 µmol/L) total bilirubin < 2.5 mg/dL (43 µmol/L) and within 2 weeks prior to registration; pregnancy test for women of childbearing potential within 2 weeks prior to registration; patients receiving systemic chemotherapy or hormonal therapy are eligible for this study (if patients have undergone CyberKnife treatment, treatment must be completed > 14 days prior to registration); patients may have received prior oral bisphosphonate therapy, such as Fosamax® or similar medications; all bisphosphonates other than the study drug must be discontinued prior to registration; women of childbearing potential and male participants must agree to practice an adequate means of birth control throughout their participation in the study; patients must sign study specific informed consent prior to study entry; patients with brain metastases and/or spinal cord compression are excluded (patients with no evidence of disease in the brain after treatment for brain metastases are eligible); patients with painful bone metastases are not permitted until these bone metastases are successfully treated (for example by external beam irradiation) prior to registration, and the patient has stable pain for at least 2 weeks after that treatment (Stable pain is defined for this study as a patient response of 1, 2, or 3 on Questions 4 and 5 of The Brief Pain Inventory (BPI); patients who have had prior treatment with Strontium-89 or Samarium-153 for bone metastases are excluded; no treatment for more than 6 months with IV bisphosphonates prior to study entry; no treatment with calcitonin, mithramycin, or gallium nitrate within 2 weeks prior to registration; no evidence in the six months prior to study entry of uncontrolled congestive heart failure, hypertension refractory to treatment, or symptomatic coronary artery disease; no current, active dental problems within 4 weeks of registration, including infection of the teeth or jawbone (maxilla or mandible); dental or fixture trauma; current or prior diagnosis of osteonecrosis of the jaw (ONJ); exposed bone in the mouth; or slow healing after dental procedures; no dental surgery (e.g., extractions, implants) within 6 weeks of study entry and while receiving study treatment; patients with Acquired Immune Deficiency Syndrome (AIDS) are excluded; pregnant or lactating patients are excluded. Treatment: Arm 1: Zoledronic acid plus vitamin D and calcium supplement Arm 2: Zoledronic acid plus vitamin D and calcium supplement plus single dose of Sr-89 or Sm-153 Study size: 352   RTOG 0537 Number: RTOG 0537 Title: A Phase II/III Study Comparing Acupuncture-like Transcutaneous Electrical Nerve Stimulation (ALTENS) Versus Pilocarpine in Treating Early Radiation-Induced Xerostomia Eligibility: Complete history and physical examination to demonstrate no clinical evidence of disease recurrence, including an ENT exam with a nasopharyngeal scope, if indicated, 8 weeks prior to registration; CT or MRI scan within 8 weeks prior to registration except for patients who finished radiation treatment one or more years ago and clinically there is no evidence of recurrence; Patients who have completed RT (standard or IMRT) +/- chemotherapy for head and neck cancers greater than or equal to 3 months and up to a maximum of 2 years prior to study entry and who have grade 1-2 xerostomia according to the CTCAE v.3.0 dry mouth/salivary gland xerostomia scale; Must have evidence of residual salivary function with unstimulated (basal) WSP equal or greater than 0.1 ml/min (having refrained from eating or drinking oral fluid for 2 hours prior); Patients who have received pilocarpine or cevimeline previously are eligible; patients must discontinue prior pilocarpine or cevimeline within 2 weeks prior to randomization; Zubrod performance status of 0-2; Age > 18 years; Serum pregnancy test for women of childbearing potential; women of childbearing potential and male participants must practice adequate contraception; Patient must be able to provide study-specific informed consent prior to study entry. No prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible); No patients with normal saliva production (no salivary gland changes; no xerostomia); No patients who have previously received and discontinued pilocarpine due to serious adverse events; No patients with current contraindications to pilocarpine (e.g., uncontrolled asthma, miosis, hypersensitivity); No patients who are on pilocarpine for ophthalmic or non-ophthalmic indications; No patients who are on regular medications which will induce xerostomia (e.g., tricyclic antidepressants, antihistamines with anticholinergic effects or narcotics); No severe, active co-morbidity as defined in the protocol; No pregnant females, as ALTENS stimulates acupuncture points that may be related to the Conception Meridian and, in theory, may affect uterine function; No patients who have Sjögren's Syndrome. Treatment Phase II Component ALTENS (given with Codetron®) 2x weekly for 12 weeks Phase III Component Stratify: Prior use of pilocarpine Time from cancer treatment Randomize: Arm 1: Pilocarpine, t.i.d., for 12 weeks Arm 2: ALTENS (given with Codetron®) 2x weekly for 12 weeks Study size: Phase II component, 45 patients Phase III component, 144 patients   RTOG 0614 Number: RTOG 0614 Title: A Randomized, Phase III, Double-Blind, Placebo-Controlled Trial of Memantine for Prevention of Cognitive Dysfunction in Patients Receiving Whole-Brain Radiotherapy Eligibility: Pathologically (histologically or cytologically) proven diagnosis of solid tumor malignancy 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 metastasis or brain metastasis). Brain metastases must be visible on contrast-enhanced MRI or a contrast enhanced CT for patients unable to have an MRI performed <28 days prior to study entry (an allowed exception, regarding ability to image brain metastases, would be patients who had undergone radiosurgery or surgical resection and are planning adjuvant WBRT do not have to have visible disease but do need a baseline MRI). Patients unable to undergo MR imaging because of non-compatible devices can be enrolled, provided the contrast-enhanced CT scans are obtained and are of sufficient quality. Patients must have stable systemic disease (i.e. no evidence of systemic disease progression >3 months prior to study entry). Patients who have brain metastases at initial presentation are eligible and do not need to demonstrate 3 months of stable scans. Karnofsky Performance Status of >70 within 28 days prior to study entry. Age > 18. Serum creatinine and total bilirubin obtained <28 days prior to study entry; with adequate kidney and liver function as defined in the protocol. BUN < 20 mg/dL <28 days prior to study entry; MMSE score >18 within 28 days prior to study entry. Patient must provide study specific informed consent prior to study entry. Patients may have had prior therapy for brain metastasis, including radiosurgery and surgical resection. Patients should have completed prior therapy at least 14 days but no longer than 56 days prior to study entry. Patients receiving systemic therapy are eligible for this study if given >14 days prior to study entry and given no sooner than >14 days post RT completion. Negative serum pregnancy test (in women of childbearing potential) <7 days prior to study entry. Women of childbearing potential and men who are sexually active must practice adequate contraception. Complete history and general physical examination < 28 days prior to study entry. No prior allergic reaction to memantine. No current alcohol or drug abuse. No chronic short-acting benzodiazepine use. No intractable seizures while on adequate anticonvulsant therapy. Treatment Arm 1 WBRT 37.5Gy/15 fractions + memantine * Arm 2 WBRT 37.5Gy/15 fractions + placebo* *Memantine/placebo to be administered during and after WBRT for a total of 24 weeks. Study size: 536   RTOG 0631 Number: RTOG 0631 Title: Phase II/III Study of Image-Guided Radiosurgery/SBRT for Localized Spine Metastasis Eligibility: The patient must have localized spine metastasis from the C1 to L5 levels by a screening imaging study (bone scan, PET, CT, or MRI) [a solitary spine metastasis; two separate spine levels; or up to 3 separate sites (e.g., C5, T5-6, and T12) are permitted.] Each of the separate sites may have a maximal involvement of 2 contiguous vertebral bodies. Zubrod Performance Status 0-2; Age > 18; Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential; Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control; Patients with epidural compression are eligible provided that there is a > 3 mm gap between the spinal cord and the edge of the epidural lesion. Patients with a paraspinal mass < 5 cm in the greatest dimension and that is contiguous with spine metastasis are eligible. Patients must provide study specific informed consent prior to study entry. Radiosurgery/SBRT Radiosurgery/SBRT: Single fraction dose of 16 Gy Study size: Phase II component: 43 Phase III component: 240   RTOG 0831 Number: RTOG 0831 Title: A Randomized, Double-Blinded, Placebo-Controlled Phase III Trial To Evaluate The Effectiveness Of A Phosphodiesterase 5 Inhibitor, Tadalafil, In Prevention Of Erectile Dysfunction In Patients Treated With Radiotherapy For Prostate Cancer [Prevention of Erectile Dysfunction Study (PEDS)] Eligibility: Clinical stage T1b-T2b (AJCC, 6th ed.) adenocarcinoma of the prostate within 6 months of registration. Clinically negative lymph nodes as established by imaging (pelvic abdominal CT or MR), nodal sampling, or dissection within 3 months prior to registration. Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are < 1.5 cm. Lymph node assessment is optional, and at investigator discretion, for patients with Gleason Score <7. No evidence of bone metastases (M0) on bone scan within 3 months prior to registration. Equivocal bone scan findings are allowed if plain films are negative for metastasis. Bone metastases assessment is optional, and at investigator discretion, for patients with Gleason Score <7. Baseline serum PSA value performed with an FDA-approved assay (e.g., Abbott, Hybritech) within 3 months prior to registration. Any of the following combinations of factors (Note: tumor found in 1 or both lobes on biopsy, but not palpable, will not alter T stage): T1b-T2b disease, Gleason Score <7 and serum total PSA that is <20 ng/ml or T1b-T2b disease, Gleason Score >7 and PSA that is <15 ng/ml Serum total testosterone level prior to the initiation of RT within normal range according to institutional guidelines. Zubrod Performance Status 0 or 1. Age > 18 years. Treatment that will consist of either external beam RT alone to the prostate ± seminal vesicles only at a dose between 72 Gy and 79.2 Gy or brachytherapy alone (Note: treatment with combined external RT and brachytherapy excludes patient participation). Completion of entire IIEF Form (QF Form) prior to registration. Pretreatment (before starting prostate cancer treatment) erectile function as measured by IIEF (QF form) Question 1, "How often were you able to get an erection during sexual activity?" - with responses of: "sometimes (about half the time)" [response 3] or "most times (much more than half the time)" [response 4] or "almost always/always" [response 5] History of prior tadalafil use: Document usual dosage per sexual encounter, date of last dose, and patient's response (No; Yes-Unsatisfactory Response; Yes-Satisfactory Response). Regardless of past experience, the patient is eligible if he agrees to adhere to protocol and take only tadalafil or placebo prescribed on study. Although patients with partners are targeted for recruitment, patients without partners or without partners willing to participate are eligible. Patients (and spouses/partners, if willing to participate) must be able to provide study-specific informed consent. No participation in another medical research study that involves the treatment of ED. No previous or concomitant invasive cancer (AJCC Stage >0), other than localized basal cell or squamous cell skin carcinoma (AJCC Stage 0-II), or a hematological malignancy (e.g., leukemia, lymphoma, myeloma) unless continually disease free for at least 5 years. No history of myocardial infarction within the last year. No heart failure in the last 6 months. No uncontrolled arrhythmias, hypotension (<90/50mm Hg), or uncontrolled hypertension (>170/100 mm Hg). No stroke within the last 6 months. No use of LHRH agonist androgen suppression (e.g., Lupron, Zoladex), anti-androgen (e.g., Casodex, Eulexin, Nilandron), or estrogenic (e.g., diethylstilbestrol) agents within the last 6 months. No current use of any organic nitrate or as needed nitrates (e.g., use of nitroglycerin) or current use of cimetidine, ketoconazole, itraconazole, erythromycin, or ritonavir. No known moderate to severe renal insufficiency or end-stage renal disease. No known severe hepatic impairment. No use of mechanical (vacuum) devices, intracorporeal, intraurethral, topical, or oral (sildenafil, tadalafil, vardenafil) agents as therapy for ED or supplements to enhance sexual function within 5-7 days prior to the start of RT. Patients who discontinue these therapies remain eligible if they can meet eligibility in Section 3.1 of the protocol. No pretreatment (before starting prostate cancer treatment) ED as measured by IIEF (QF form) Question 1, "How often were you able to get an erection during sexual activity?" - with responses of: "no sexual activity" [response 0] or "almost never/never" [response 1] or "a few times (much less than half the time)" [response 2] No prior penile implant or history of bilateral orchiectomy. No prior prostatectomy, prostatic cryosurgery or high-intensity focused ultrasound (HIFU), radionuclide prostate brachytherapy, or chemotherapy for prostate cancer. No prior or anticipated combined external RT and brachytherapy. No prior or anticipated external RT to the pelvic ± para-aortic lymph nodes. No Acquired Immune Deficiency Syndrome (AIDS) based upon the current CDC definition. No anatomical genital abnormalities or concurrent conditions that in the estimation of the physician would prohibit sexual intercourse or prevent study completion. No major medical or psychiatric illness which, in the opinion of the investigator, would prevent completion of treatment or would interfere with follow-up. Spouse/Partner Eligibility Criteria A male or female partner is eligible. Spouse/partner must provide signed study-specific informed consent. Treatment Stratify: Age 1. <65 years 2. >65 years RT Treatment 1. External radiation therapy 2. Brachytherapy Randomize: Arm 1: Tadalafil started within 7 days after the start of radiation therapy and continued for 168 days (24 weeks) Arm 2: Placebo started within 7 days after the start of radiation therapy and continued for 168 days (24 weeks) Study size: 218   RTOG 0841 Number: RTOG 0841 Title: Efficiency Of Screening For Depression In Cancer Patients Receiving Radiotherapy Eligibility: Patients about to begin or within 2 weeks of beginning radiation therapy for their first diagnosis of any tumor type (patients may have had or be on combination therapy with surgery, chemotherapy, hormone therapy or immunotherapy); patient is not considered suicidal, psychotic, or otherwise unfit for study participation by cancer center staff clinical judgment; patients with Stage I-IV (where applicable) cancer are eligible; Zubrod performance status 0-1; age >21; patient must be able to speak and read English sufficiently to complete screening instruments; patient must have existing land line or cellular telephone service; patients receiving psychotropic medication are eligible; patients with a pre-existing diagnosis of depression and who are currently receiving psychotherapy or pharmacotherapy for depression at screening are eligible; patient must be able to provide study-specific informed consent prior to study entry. Patient must not have a medical or psychiatric condition which, in the opinion of the investigator, would potentially pose a risk to the patient as a result of participation in this trial; no patients who are mentally incompetent or who are receiving hospice care. Treatment Registration The member site will identify patients and obtain informed consent Stage I Screening (Patient Questionnaires) All Patients Patients complete the Hopkins Symptom Checklist (HSCL-25), the 9-item Patient Health Questionnaire (PHQ-9), which includes a 2-item Patient Health Questionnaire (PHQ-2), and a Health Status Questionnaire during a routine visit at the member site. Stage II Evaluation (Telephone Interviews, within 2 weeks) Patients identified as having major depression through the questionnaires The study investigators will oversee a telephone interview conducted through a centralized office of trained interviewers using selected modules of the Structured Clinical Interview for Diagnosis- DSM-IV (SCID) and the Assessment of Mental Health Services and Barriers to Care for patients. The clinical interviewer will mail lists of resources in the community to patients with a research diagnosis of depression and ask the patient for permission to provide her/his results to their oncology team. Follow-up Telephone Assessment of Depressed Patients (at 3 months) Patients identified as having a research diagnosis of a depressive disorder during the telephone interview Patients will be reassessed for diagnosis and depressive symptoms using the PHQ-9, the HSCL-25 and the SCID through a telephone interview conducted by the study's centralized office. The Assessment of Mental Health Services and Barriers to Care will also be administered at this time. Treatment options and resources will be discussed again with patients who remain depressed, but who are not in treatment. Study size: 400 patients