1. Clinical Trials The Way We Make Progress Against Disease

2. What Are Clinical Trials? Research studies involving people Try to answer scientific questions and find better ways to prevent, diagnose, or treat disease

3. Why Is Participation in Clinical Trials Important? The more people take part, the faster we can: - Answer critical research questions - Find better treatments and ways to prevent disease

4. Do Many People Take Part in Clinical Trials? Few people participate

5. What Are Different Types of Clinical Trials? Prevention Treatment Tumor or normal tissue studies Early detection/screening Diagnostic Quality of life/supportive care

6. Prevention Trials Evaluate the effectiveness of ways to reduce the risk of a particular disease Enroll healthy people at high risk for developing that disease

7. Treatment Trials What new treatments can help people with a particular disease? What is the most effective treatment for people with that disease?

8. Clinical Trial Phases Phase 1 trials How does the agent affect the human body? What dosage is safe? What is the best dose to use for phase 2 trials?

9. Clinical Trial Phases Phase 2 trials Does the agent or intervention have an effect on a specific disease? The majority of trials in neuroendocrine cancers are phase II trials

10. Clinical Trial Phases Phase 3 trials Is the new agent or intervention (or new use of a treatment) better than the standard? Require large numbers of patients to answer questions

11. Randomized Phase III Trials Participants have an equal chance to be assigned to one of two or more groups: One gets the most widely accepted treatment (standard treatment) The other gets the new treatment being tested, which researchers hope and have reason to believe will be better than the standard treatment

12. Randomization

13. Why is Randomization Important? So all groups are as alike as possible (Even when unintended, selection bias is a major limitation to non-randomized studies.) Provides the best way to prove the effectiveness of a new agent or intervention

14. Clinical Trial Protocol A recipe or blueprint Strict scientific guidelines: --Purpose of study --How many people will participate --Who is eligible to participate --How the study will be carried out --What information will be gathered about participants --Endpoints

15. Benefits of Participation Possible benefits: Patients will receive, at a minimum, the best standard treatment (if one exists) If the new treatment or intervention is proven to work, patients may be among the first to benefit Patients have a chance to help others and improve patient care

16. Risks of Participation Possible risks: New treatments or interventions under study are not always better than, or even as good as, standard care Even if a new treatment has benefits, it may not work for every patient

17. Patient Protection Federal regulations ensure that people are told about the benefits, risks, and purpose of research before they agree to participate

18. How Are Patients’ Rights Protected? Informed consent Scientific review Institutional review boards (IRBs) Data safety and monitoring boards (DSMBs)

19. How Are Patients’ Rights Protected? Informed Consent: Purpose Procedures Potential risks and benefits Individual rights

20. How Are Patients’ Rights Protected? Scientific review (NCI designated Cancer Centers require this for all trials) Institutional review boards (IRBs) are required by federal law for trials that are: --Federally funded --Subject to FDA regulation

21. How Are Patients’ Rights Protected? Data and safety monitoring boards: Ensure that risks are minimized Ensure data integrity Stop a trial if safety concerns arise or objectives have been met

22. Why Do So Few People Participate in Clinical Trials? Sometimes patients: Don’t know about clinical trials Don’t have access to clinical trials May be afraid or suspicious of research Can’t afford to participate May not want to go against health care provider’s wishes

23. Why Do So Few People Participate in Clinical Trials? Health care providers might: Lack awareness of appropriate clinical trials Be unwilling to “lose control” of a person’s care Believe that standard therapy is best Be concerned that clinical trials add administrative burdens

24. DFHCC Clinical Trials in Neuroendocrine Tumors Therapeutic: –A multicenter, randomized, blinded efficacy and safety study of pasireotide LAR vs octreotide LAR in patients with metastatic carcinoid tumors whose disease-related symptoms are inadequately controlled by somatostatin analogues. –Phase III Prospective Randomized Comparison of Depot Octreotide plus Interferon Alpha Versus Depot Octreotide Plus Bevacizumab (NSC#704865) in Advanced, Poor Prognosis Carcinoid Patients Non-Therapeutic: –Sample Collection in Patients with Neuroendocrine –Protein Expression in Carcinoid Tumors

25. DFHCC Clinical Trials in Neuroendocrine Tumors Therapeutic: (Pending) –Ph II AMG479 in Carcinoid and Panc Neuroendocrine –Octreotide Implant in Carcinoid –LX 1006 in Carcinoid pts. Refractory to Octreotide

28. Where to Find Additional Clinical Trial Information Your health care provider National Library of Medicine www.ClinicalTrials.gov 

29. Neuroendocrine Cancers The important role of a multimodality approach to the disease from time of diagnosis but continuing throughout the course of the patient’s care, including: –Surgeons for resections of primary lesions and where appropriate, metastatic disease –Interventional and/or Vascular radiologists for directed therapies (such as RFA or chemoembolization) especially for liver lesions –Medical oncologists for systemic therapy, including LAR octreotide treatment as well as various chemotherapeutic agents as appropriate –Radiation oncologists for treatment of appropriate disease such as painful bony lesions.

30. Neuroendocrine Tumors (conclusion continued) The variable natural history of these tumors. –Some individuals, such as this patient, have a relatively indolent history, doing quite well despite metastatic disease –Others have a more aggressive course requiring ongoing chemotherapy or chemoembolization to control their disease and symptoms

31. Neuroendocrine Tumors (conclusion continued) Thus, this is a disease where it is very important that each patient be evaluated carefully by the different disciplines and has disease tailored appropriately.