0 Dead. NCI Protocol #: CITN-04 Version Date: 27 Jan 2016 82 APPENDIX B CTEP MULTICENTER GUIDELINES If an institution wishes to collaborate with ot her participating instit utions in performing a CTEP sponsored research protocol, then the following guidelines must be followed. Responsibility of the Protocol Chair  The Protocol Chair will be the single liaison with the CTEP Protocol and Information Office (PIO). The Protocol Chair is res ponsible for the coordination, development, submission, and approval of the protocol as well as its subsequent amendments. The protocol must not be rewritten or modified by anyone other th an the Protocol Chair. There will be only one version of the protocol, a nd each participating institution will use that document. The Protocol Chair is responsible fo r assuring that all part icipating institutions are using the correct ve rsion of the protocol.  The Protocol Chair is responsible for the ove rall conduct of the study at all participating institutions and for monitori ng its progress. All reporting re quirements to CTEP are the responsibility of the Protocol Chair in conjunction with the CITN Coordinating Center.  The Protocol Chair is responsible for the timely review of Adverse Ev ents (AE) to ensure safety of the patients.  The Protocol Chair will be responsible for the review of and timely submission of data for study analysis. Responsibilities of the CITN Coordinating Center (Central Operations and Statistical Center, COSC)  Each participating institution wi ll have an appropriate assura nce on file with the Office for Human Research Protection (OHRP), NIH. The Coordinating Center is responsible for assuring that each participating institution has an OHRP assurance and verifies with CTSU, Regulatory Support System, (RSS) that each inst itution has obtained IRB approval prior to site activation.  Prior to the activation of the protocol at each participating ins titution, an OHRP form 310 (documentation of IRB approval) must be submitted to CTSU, (RSS).  The Cancer Trials Support Unit is responsible for central patient registration through the OPEN registration system. The Coordinating Ce nter is responsible for assuring that IRB approval has been obtained at each participati ng site before the first patient registration from that site.  The Coordinating Center is responsible for the preparation of all submitted data for review by the Protocol Chair.  The Coordinating Center will maintain documentation of AE reports. Participating institutions will report to the Coordinating Center who in turn report to CTEP or the FDA as appropriate. The Coordinating Center will su bmit AE reports to the Protocol Chair for timely review.  Audits may be accomplished by selecting a percentage of patient records on-site at participating sites. If the NCI chooses to have an audit at th e Coordinating Center, then the Coordinating Center is responsible for havi ng all source documents, research records, all IRB approval documents, NCI Drug Accountability Record forms, patient registration lists, response assessments scans, x-rays , etc. available for the audit. NCI Protocol #: CITN-04 Version Date: 27 Jan 2016 83 Inclusion of Multicenter Guid elines in the Protocol  The protocol will include the following minimum information:  The title page must include the name and address of each participating institution and the name, telephone number and e-mail address of the responsible investigator at each participating institution.  The Coordinating Center must be designated on the title page.  Central registration of patient s is required. The procedures for registration must be stated in the protocol.  Data collection forms should be of a common format. Sample forms should be submitted with the protocol. The frequency and timing of data submission forms to the Coordinating Center should be stated.  Describe how AEs will be reported from the pa rticipating institutions, either directly to CTEP or through the Coordinating Center.  Describe how Safety Reports and Action Le tters from CTEP will be distributed to participating institutions. NCI Protocol #: CITN-04 Version Date: 27 Jan 2016 84 APPENDIX C INFORMATION ON POSSIBLE DRUG INTERACTIONS Information on Possible Interactions with Ot her Agents for Patients and Their Caregivers and Non-Study Healthcare Team The patient ____________________________ is enrolled on a clinical trial using the experimental agent INCB024360 (an IDO Inhibitor). This clinical trial is sponsored by the National Cancer Institute. This form is addr essed to the patient, but includes important information for others who care for this patient. INCB024360 interacts with many drugs that are processed by your liver; it is very important to tell your study doctors about all of your medicine before you start this st udy. It is also very important to tell them if you stop taking any regular medici ne, or if you start taking a new medicine while you take part in this study. When you talk about your medicine with your study doctor, include medicine you buy without a prescription at the dr ug store (over-the-counter remedy) or herbal supplements. Many healthcare prescribers can write prescripti ons. You must also tell your other prescribers (doctors, physicians’ assistants or nurse practitione rs) that you are taking part in a clinical trial. Bring this paper with you and keep the attached information card in your wallet . These are the things that you and they need to know: INCB024360 interacts with (a) certain speci fic enzyme(s) in your liver.  The enzyme(s) in question is UGT1A9. Hypothe tically, inhibition of IDO could cause an increase in serotonin levels that could precipitate a cluster of adverse events termed serotonin syndrome. This rare syndrome has been associated with some MAO inhibitors and with combinations of serotonergic dr ugs. Symptom onset is usually rapid, often occurring within minutes, and encompasse s a wide range of clinical findings: o Mild symptoms may only consist of in creased heart rate, shivering, sweating, dilated pupils, and over-responsive reflexes. o Moderate symptoms may include additional abnormalities such as hyperactive bowel sounds, high blood pressure, and hyperthermia. A temperature as high as 40°C (104°F) is common in moderate int oxication. Mental status changes include hypervigilance and agitation. o Severe symptoms include severe increases in heart rate and blood pressure that may lead to shock. In life-thr eatening cases, temperature may rise to above 41.1°C (106.0°F). Other abnormalities include metabolic acidosis, rhabdomyolysis, seizures, renal failure, and disseminated in travascular coagulation; these effects usually arise as a consequence of hyperthermia.  INCB024360 must be used very carefully with ot her medicines that need these liver enzymes to be effective or to be cleared from your system.  You and healthcare providers w ho prescribe drugs for you must be careful about adding or removing any drug in this category.  Before you start the study, your study doctor wi ll work with your regular prescriber to NCI Protocol #: CITN-04 Version Date: 27 Jan 2016 85 switch any medicines that are considered “strong inducers/inhi bitors of UGT1A9 ” Inhibitors include acitretin, amitriptyline, andr osterone, cyclosporine, dasatinib, diclofenac, diflunisal, efavirenz, erlotinib, estradiol ( 17-beta), flutamide, geftinib, gemfibrozil, glycyrrhetinic acid glycyrrhizin, imatini b, imipramine, ketoconazole, linoleic acid, mefenamic acid, mycophenolic acid, ni flumic acid, nilotinib, phenobartital, phenylbutazone, phenytoin, and probenecid pro pofol, quinidine, ritonavir, Sorafenib, sulfinpyrazone, valpro ic acid, and verapmil  Several patients on INCB024360 and coumadin (an anticoagulant blood thinner) have had elevated INRs, possibly from interactions wi th the CYP enzyme system. Thus, patients on coumadin should not be entered onto trial. If coumadin needs to be administrated during or after the trial, INR needs to be monitored closely.  Your prescriber should consult a medical refere nce to see if any medicine they want to prescribe is on a list of drugs to avoid.