MD Anderson Cancer Center CCOP Research Base Update 2011

1. MD Anderson Cancer Center CCOP Research Base Update 2011 Michael J. Fisch, MD, MPH, FACP Chair, Department of General Oncology Division of Cancer Medicine mfisch@mdanderson.org Twitter: @fischmd, @JSupportOncol

2. Objectives • Review our membership and accrual • Discuss some study data • Describe and discuss our active studies • Summarize CCOP Strategic Plan • Explore our future together • What do we do well? • What will be the indicators of success in the future?

5. Active Treatment Protocols

6. Treatment: Active 2005-0839 (NCI 7341)A Phase II Study of Gemcitabine, Paclitaxel, and Doxorubicin, with Pegfilgrastim for the Treatment of Patients with Metastatic Transitional Cell Carcinoma and Renal Insufficiency Principal Investigator: Lance C. Pagliaro, MD, MD Anderson Cancer Center Methodology: Single-arm phase II protocol Patients with CrCL< 60 ml/min receive • doxorubicin 40 mg/m2 IV over 20 min; • paclitaxel 135 mg/m2 IV over 60 min; • gemcitabine 900 mg/m2 IV over 90 min; Pegfilgrastim 6 mg SC on day 1 or day 2 Courses repeated every 14 days Patient Population: Metastatic or unresectable transitional cell (TCC) carcinoma of bladder, urethra or upper urinary tract. Mixed TCC and variant histologies (small cell, squamous, adenocarcinoma, sarcoma) are permitted if present in < 50% of the biopsy specimen. Accrual 28 patients / Goal 72 Top Enrolling Sites: MD Anderson, Ozarks CCOP Preliminary Results: Poster presented at GU ASCO February, 2011

7. Closed Treatment Protocols

8. Treatment: CNPE ID00-156 (NCI 3410)A Prospective Randomized Phase III Trial Comparing Consolidation Therapy with or without Strontium-89 Following Induction Chemotherapy in Androgen-Independent Prostate Cancer Principal Investigator: Shi-Ming Tu, MD, MD Anderson Cancer Center Patient Population: A total of 265 patients with androgen-independent prostate cancer were enrolled. Closed to new patient entry 10/20/2010. Top Enrolling CCOP Sites: MD Anderson – Orlando, Marshfield Clinic, Wichita CCOP, Central Illinois CCOP Preliminary Results: Pending RANDOM I Z E Sr-89 plus doxorubicin x 6 weeks Option 1 Ketoconazole/doxorubicin Alternating with Estramustine/vinblastine Option 2 Prednisone/docetaxel Clinical Response 16 weeks Doxorubicin x 6 weeks

9. Treatment: CNPE 2004-0662 (NCI 6636)A Randomized, Factorial-Design, Phase II Trial of Temozolomide Alone and in Combination with Possible Permutations of Thalidomide, Isotrentinoin and/or Celecoxib as Post-Radiation Adjuvant Therapy of Glioblastoma Multiforme Principal Investigator:Mark R. Gilbert, MD, M. D. Anderson Cancer Center Patient Population: 178 patients with a diagnosis of supratentorial glioblastoma multiforme enrolled. Closed to new patient entry 02/24/2011. Top Enrolling CCOP Sites: Atlanta CCOP, Kansas City CCOP, Central Illinois CCOP Preliminary Results: Pending

10. Treatment: CNPE 2004-0305 (NCI 6485)A Phase II Study of Rituximab-CHOP with Pegylated Liposomal Doxorubicin in Patients Older than 60 Years of Age with Untreated Aggressive B-Cell Non-Hodgkin’s Lymphoma Methodology: Rituximab 375 mg/m2 IVPB on day 1, administered 1st Cyclophosphamide 750 mg/m2 IVPB on day 1 Pegylated liposomal doxorubicin 40 mg/m2 IV over 1hr day 1 Vincristine 2.0 mg IV, day 1 Prednisone 40 mg/m2 PO days 1-5 GCSF 5 mcg/kg, SC daily, start on day 5, until neutrophil recovery (>3000/ul) OR Pegylated GCSF 6 mg SC x 1 (24 hours after chemotherapy) Patient Population: At total of 80 patients, older than 60 years of age with untreated aggressive B-cell NHL, enrolled. Closed to new patient entry 05/18/2009. Top Enrolling CCOP Sites:Maimonides Medical Center, Grand Rapids CCOP

11. Treatment: CNPE 2004-0305 (NCI 6485)A Phase II Study of Rituximab-CHOP with Pegylated Liposomal Doxorubicin in Patients Older than 60 Years of Age with Untreated Aggressive B-Cell Non-Hodgkin’s Lymphoma Summary of Protocol Findings • 80 patients were enrolled on the trial and evaluated for response, cardiotoxicity, and myelosuppression. • 74 patients were evaluable for response after 4 courses of therapy. • 54 (73%) patients achieved a CR / 14 (19%) patients achieved a PR • The overall response rate was 92%. • Response assessment after 8 courses of therapy was performed on 63 evaluable patients. • The overall response rate for the 63 evaluable patients after 8 cycles was 89%.

12. Treatment: CNPE 2004-0305 (NCI 6485)A Phase II Study of Rituximab-CHOP with Pegylated Liposomal Doxorubicin in Patients Older than 60 Years of Age with Untreated Aggressive B-Cell Non-Hodgkin’s Lymphoma Summary of Protocol Findings • Of the 80 patients enrolled, 12 (15%) patients reported grade 3 cardiac events, including hypotension (3), tachycardia (1), hypertension (2), decreased ejection fraction (1), chest pain (2), arrhythmia (3), coronary artery disease (1), acute coronary syndrome and diastolic dysfunction (1), TIA (1), and pericarditis (1). • Other Grade 3-4 toxicities reported in >10% of patients were: fatigue (27), leucopenia (31), lymphopenia (35), neutropenia (34), and anemia (12).

13. Treatment: CNPE 2006-0260 (NCI 7548)Single-arm, Open-label, Phase II Trial of Rituximab plus Sargramostim for the Treatment of Newly Diagnosed Follicular B-cell Lymphoma in Adults New Principal Investigator Nathan Fowler, MD, MD Anderson Cancer Center Patient Population:A total of 52 patients with newly diagnosed follicular B cell lymphoma were enrolled. Closed to new patient entry 05/01/2009. Top Enrolling CCOP Sites: Wichita CCOP, Grand Rapids CCOP

14. Treatment: CNPE 2006-0260 (NCI 7548)Single-arm, Open-label, Phase II Trial of Rituximab plus Sargramostim for the Treatment of Newly Diagnosed Follicular B-cell Lymphoma in Adults Summary of Protocol Findings • 52 pts were enrolled on study, and all were eligible for assessment. The median age was 56 (31-78), and 62% were male. • 56% of patients had intermediate or high risk FLIPI. Fifteen (29%) pts had bulky disease (>5cm), and 29 (56%) pts had elevated B2M. • Tolerance was good; and effects attributable to GM-CSF were minor.  Absolute granulocyte count (AGC) elevation above 15K occurred in only 4% of pts; conversely, ≥ grade 3 neutropenia occurred in 8 pts. No significant infections occurred.

15. Treatment: CNPE 2006-0260 (NCI 7548)Single-arm, Open-label, Phase II Trial of Rituximab plus Sargramostim for the Treatment of Newly Diagnosed Follicular B-cell Lymphoma in Adults Summary of Protocol Findings • At 3 months, the overall response rate was 69%, including 23% of pts with a CR. With continued follow up, response rates improved (ORR 74%, CR 42%). Twenty four (46%) pts remain in remission without further treatment. At a median follow up of 14 months the median PFS of all pts was 28 months, including pts with bulky disease (median PFS of 16 mo). No difference in PFS was observed when comparing FLIPI score (0-1) vs (2-3) or B2M. • Conclusion: Rituximab plus GM-CSF is well tolerated and active in untreated pts with FL. There did not appear to be significant difference in outcomes when comparing FLIPI scores, although PFS was inferior in patients with bulky disease. Randomized studies are required to determine whether this combination is superior to rituximab as a single agent.

16. Active Cancer Control Protocols

17. Cancer Control: Active 2004-0024 (NCI CCC01-06)Chemotherapy and Mindfulness Relaxation: A Randomized Trial at M. D. Anderson Cancer Center and M. D. Anderson Community Clinical Oncology Program Principal Investigators: Jon Hunter MD, Mount Sinai Hospital, Toronto Lorenzo Cohen, PhD, MD Anderson Cancer Center Community Co-Investigator: Dedra Glover, AS, CCRP, Scott & White CCOP Methodology: Patients with newly-diagnosed cancer, who are about to undergo chemotherapy, and give informed consent, will be randomly assigned to one of three groups: • Mindfulness Relaxation group [MR]; • Relaxing Music group [RM] where participants will listen to music for the same amount of time as the MR participants receive their intervention; • Standard Care control group where participants will receive standard medical education on chemotherapy [SC]. Patient Population:The study population will consist chemotherapy naive cancer patients schedule to undergo at least 4 cycles of chemotherapy treatment. Target accrual 400 subjects (including 25 on pilot). Current accrual 284. Top Enrolling CCOP Sites: Scott & White CCOP, Michigan Cancer Research Consortium, San Juan MBCCOP

18. 2004-0024 (NCI CCC01-06)Chemotherapy and Mindfulness Relaxation: A Randomized Trial at M. D. Anderson Cancer Center and M. D. Anderson Community Clinical Oncology Program Additional training and intervention recording being held March 5, 2011. Planned protocol revision March, 2011 to remove exclusion criteria excluding patients with concrete planned immune therapy as part of the their treatment regimen and/or within 3 months of completing chemotherapy. Examples include GCSF, GMCSF,IL2, and/or Interferon.

19. 2 Weeks Provider and Patient Follow-Up Assessment Provider and Patient Follow-Up Assessment 2 Months Provider and Patient Follow-up Assessment Provider and Patient Follow-up Assessment Cancer Control: Active 2006-0198 (NCI MDA 2006-0198)CAM Use and Cancer Principal Investigator: Patricia Ann Parker, PhD, MD Anderson Cancer Center Patient Population:. Oncology nurses with regular interactions with patients who are at least one week post diagnosis of cancer and not greater than 6 months post treatment. 1360 target accrual. Top Enrolling CCOP Sites:Metro-Minnesota CCOP, Central Illinois CCOP, Grand Rapids Clinical Oncology Program, Boston Medical Center Random Assignment to Intervention or Waitlist Control Enrollment of Nurses/Providers at Participating CCOPs 1 Week Baseline Patient Assessment Baseline Provider Assessment Baseline Provider Assessment CD/Video and Resource List CD/Video and Resource List

20. Cancer Control: Active 2006-0198 (NCI MDA 2006-0198)CAM Use and Cancer Preliminary Findings – ASCO 2010 • Patients were 65% female, 86% non-Hispanic white, average age of 59 (range 23-88), and 30% had a college degree or higher. • The most common cancers were breast cancer (31%), lung cancer (12%), and colorectal cancer (10%).  • 39% indicated that they have used one or more CAM therapies following their cancer diagnosis. 

21. Cancer Control: Active 2006-0198 (NCI MDA 2006-0198)CAM Use and Cancer Preliminary Findings Continued • The most common categories of CAM used by patients were: • massage therapy (19%) • relaxation techniques (19%) • special diet (18%) • megavitamins (15%) • Reasons for using CAM included: • believes CAM beneficial (27%) • to address the emotional and spiritual aspects of the disease (23%) • and to boost immune system (21%)

22. Cancer Control: Active 2006-0198 (NCI MDA 2006-0198)CAM Use and Cancer Preliminary Findings Continued • Patients indicated that 9% of their physicians and 12% of nurses had asked them about their use of CAM at that oncology visit. • Twenty-one percent of patients reported that they initiated a discussion with their providers about their use of CAM and the most common responses were: encouraged me to continue (13%) and was neutral (7%).  • Reasons for not telling healthcare practitioners about CAM use included: my healthcare provider never asked (27%) and unsure if CAM beneficial (18%). 

23. Cancer Control: Active 2006-0198 (NCI MDA 2006-0198)CAM Use and Cancer Conclusions: More than one third of patients indicated that they used some type of CAM therapy and the majority of their providers did not ask them about their CAM use.  There remains considerable uncertainty among patients about the role of CAM in the context of cancer care.

25. Twitter Time! @fischmd @JSupportOncol @disparityreport @DrLCohen

26. Promote Clinical Trials • Instantly share IRB approved clinical trial flyers with a global audience • Uploaded approved flyer to web server • Shorten URL at http://bit.ly • Paste trial title and URL into Twitter update box. • Done! • Why Bit.ly? • Shortens URL – Twitter limits you to 140 characters • Metrics. See how many people click on your links. • This process works with any file type. It isn’t just for clinical trials.

27. Focused Discussions • Hashtags are keywords that “tag “ a conversation so that readers can easily find all relevant tweets/comments. They’re great for conferences! • Creating a hashtag is easy • 1. Any word in your tweet that starts with a pound sign is a hashtag. That’s all you have to do • Twitter makes hashtags “clickable” automatically. Clicking on one reveals the entire conversation thread. You can create your own or use others (as long as your input is relevant). • Examples: • #mdacctrials • #pediatrics • #oncology • #ASPHO2010

28. Cancer Control: Active 2006-0841 (NCI MDA 2006-0841)Randomized, Double-Blind, Placebo-Controlled Trial of Palonosetron/ Dexamethasone with or without Dronabinol for the Prevention of Chemotherapy-induced Nausea and Vomiting after Moderately Emetogenic Chemotherapy Principal Investigator: P. K. Morrow, MD, MD Anderson Cancer Center Steven Grunberg, MD, University of Vermont Community Co-Investigator: Jeffery Giguere, MD, Greenville CCOP Methodology: Palonosetron 0.25 mg IV and dexamethasone 10 mg IV 30 minutes prior to chemo administration. Randomized to take dronabinol 5 mg or matched placebo: 1 tablet by mouth 3 times a day for 5 days beginning 30 minutes before chemotherapy. Follow-up physical examination and assessment between day14 through 28. Primary endpoint will be Total Protection: No Vomiting, No Rescue Therapy and no Nausea during the overall (0-120 hour) period. Patient Population: Population will be 100 patients in each treatment group (200 patients total). Patients ≥18 years old, documented solid tumor, receiving first time chemotherapy. Currently 40 enrolled of 200 target accrual. Enrolling CCOP Sites: Christus St. Frances Cabrini, Marshfield Clinic, Greenville CCOP

29. Cancer Control: Active 2006-0841 (NCI MDA 2006-0841) Dronabinol/Placebo for the Prevention of CINV for Moderately Emetogenic Chemotherapy • Planned protocol revision March, 2011 • Allow the addition of regimens that give taxanes before Adriamycin and/or Cytoxan • Patients will be eligible after any number of cycles if • taxane given as part of planned regimen such T→AC • Patient has no N/V with taxane cycles

30. Cancer Control: Active 2008-0005 (NCI MDA 2008-0005)Phase II, Randomized, Double Blind Comparison of CASAD vs. Placebo for the Treatment and Prevention of Diarrhea in Patients with Metastatic Colorectal Cancer Principal Investigator: Bryan Kee, MD, M. D. Anderson Cancer Center Methodology: CASAD / placebo will be provided by Salient Pharmaceuticals in capsules that are taken as 2 capsules four times daily. Recently revised and sent to sites for approval. Major changes: inclusion of patients with ostomies, less restrictive lab requirements including ANC, and revision of UGT1A1 criteria. Patient Population: A maximum of 100 patients will be randomized equally between two arms, 50 per arm. Current accrual 56. Enrolling CCOP Sites: Scott & White CCOP, Greenville CCOP, Columbia River CCOP 6 Weeks CASAD -------------------------- Off Study/Optional Additional 6 Weeks Placebo -------------------------- Off Study/Optional Additional 6 Weeks R

31. Cancer Control: Active 2007-0914 (NCI 2007-0914a)A Multi-Center Study in Patients Undergoing Anthracycline-Based Chemotherapy to Assess the Effectiveness of Using Biomarkers to Detect and Identify Cardiotoxicity and Describe Treatment Principal Investigator: Daniel J. Lenihan, MD, Vanderbilt University Michael Fisch, MD, MD Anderson Cancer Center Community Co-Investigator: Steven Wolff, MD, Meharry Medical College MBCCOP Methodology: The biomarkers (BNP and Troponin I) will be obtained as a point of care test with meter, kits, controls and training provided by the protocol. Patients will be assessed during each visit prior to each cycle of therapy until therapy completion and then at 6 and 12 months after the initiation of chemotherapy to identify cardiotoxicity. Patient Population: A total of 830 patients starting a new anthracycline chemotherapy regimen will be enrolled. Enrolling CCOP Sites: Meters, kits and controls have been provided to 18 CCOP, Main Member and academic sites. Additional meters will be available in March, 2011. Currently 9 enrolled of 830 target.

32. Cancer Control: Active 2007-0914 (NCI 2007-0914a)A Multi-Center Study in Patients Undergoing Anthracycline-Based Chemotherapy to Assess the Effectiveness of Using Biomarkers to Detect and Identify Cardiotoxicity and Describe Treatment Eligible Diseases • Most enrollments will be patients with Non-Hodgkin’s Lymphoma or breast cancer • Can be any disease being treated with a regimen that uses an anthracycline including: Hodgkin’s, multiple myeloma, AML, ALL, sarcoma, Kaposi’s sarcoma, bladder, SCLC, NSCLC, gastric, ovarian and prostate

33. Cancer Control: Active 2007-0914 (NCI 2007-0914a)A Multi-Center Study in Patients Undergoing Anthracycline-Based Chemotherapy to Assess the Effectiveness of Using Biomarkers to Detect and Identify Cardiotoxicity and Describe Treatment Acceptable Anthracyclines • doxorubicin (Adriamycin) • doxorubicin liposomal (Doxil) • daunorubicin (Cerubidine) • daunorubicin liposomal (DaunoXome) • epirubicin (Ellence) • idarubicin (Idamycin) • mitoxantrone (Novantrone) • valrubicin (Valstar)

34. Cancer Control: Active 2007-0914 (NCI 2007-0914a)A Multi-Center Study in Patients Undergoing Anthracycline-Based Chemotherapy to Assess the Effectiveness of Using Biomarkers to Detect and Identify Cardiotoxicity and Describe Treatment Length of anthracycline regimen: • Any, Q14 days, Q21 days, Q28 days Anthracycline administration: • Bolus or continuous infusion Minimum anthracycline dose: • any Anthracycline regimen: • single agent or multiple agent regimen

35. Cancer Control: Active 2007-0914 (NCI 2007-0914a)A Multi-Center Study in Patients Undergoing Anthracycline-Based Chemotherapy to Assess the Effectiveness of Using Biomarkers to Detect and Identify Cardiotoxicity and Describe Treatment Echocardiogram • Prefer echocardiogram • May use Muga scan if used consistently throughout the trial • Muga provides limited information, is more expensive, and exposes patient to more radiation Protocol revision in progress to clarify this point

36. Cancer Control: Active 2009-0288 (MDA 2009-0288)Comparative Study of Oncologist Recommended, Home-Based Exercise Program and Relaxation Training for Physical Functioning and Symptom Control in Colon Cancer Patients Principal Investigator: Karen Basen-Engquist, PhD, MD Anderson Cancer Center Methodology: Patient Population:A total of 150 patients with metastatic colon cancer will be accrued to this protocol. Enrolling CCOP Pilot Sites: Wichita CCOP, Scott & White CCOP, Michigan Cancer Research Consortium. Currently 2 enrolled of 150 target.

37. Closed Cancer Control Protocols

38. Cancer Control: CNPE 2004-0728 (NCI CCC 03-27) Prevention of Cisplatin- or Oxaliplatin-induced Peripheral Neuropathy with Alpha-lipoic Acid: A Placebo-controlled Phase III Trial Principal Investigator: Ying Guo, MD, MD Anderson Cancer Center Methodology: Patient Population: A total of 244 patients who were scheduled to receive chemotherapy that contains platinum in the regimen were enrolled. Closed to new patient enrollment 11/02/2009. Top Enrolling CCOP Sites: Metro-Minnesota CCOP, Wichita CCOP, Greenville CCOP, Marshfield Clinic, Christus St Frances Cabrini Hospital

39. Cancer Control: CNPE 2004-0728 (NCI CCC 03-27) Prevention of Cisplatin- or Oxaliplatin-induced Peripheral Neuropathy with Alpha-lipoic Acid: A Placebo-controlled Phase III Trial Of 243 pts randomized, 121 pts (51%) completed treatment for 12 weeks. At 24 weeks, only 34 evaluable pts remained in the ALA group, and 36 in the placebo group (p= 0.75). No statistical difference was noted in dose intensity for the oxaliplatin arm of the ALA group and the placebo group (median of 765 mg/m2 vs. 1020 mg/m2, p=0.18). No significant differences were noted for either FACT/GOG-NTX scores (p=0.70), neurotoxicity (p=0.87), or best tumor responses between the 2 groups (p=0.85).

40. Cancer Control: CNPE 2004-0728 (NCI CCC 03-27) Prevention of Cisplatin- or Oxaliplatin-induced Peripheral Neuropathy with Alpha-lipoic Acid: A Placebo-controlled Phase III Trial Conclusions: • Oral ALA 600 mg PO TID was ineffective at preventing neurotoxicity caused by oxaliplatin or cisplatin. • Intense schedules of oral agents in the symptom/toxicity prevention setting created adherence challenges due to pill size and frequency of administration. • Poor adherence might affect the power to detect ALA’s effectiveness in this trial. • Innovative drug delivery and trial designs are needed to further explore alpha lipoic acid in the prevention and/or reduction of chemotherapy-induced neuropathy.

41. Upcoming Protocols

42. Cancer Control: Proposed 2010-0547 (MDA 04-01)A Phase III Prospective Randomized Trial of Acupuncture for Treatment of Radiation-Induced Xerostomia in Patients with Head and Neck Cancer Principal Investigator: Joseph S. Chiang, MD, MD Anderson Cancer Center Methodology: Protocol Status: NCI Approved, IRB Approval Pending Patient Population: A total of 150 patients who have received radiation for the treatment of head and neck cancer will be enrolled. Enrolling CCOP Sites: Sites should have a relationship with board certified acupuncturists who will participate in training to do fixed acupuncture on a placebo controlled protocol.

43. Cancer Control: Proposed 2010-0547 (MDA 04-01)A Phase III Prospective Randomized Trial of Acupuncture for Treatment of Radiation-Induced Xerostomia in Patients with Head and Neck Cancer • Conference call/webinar to be held with interested sites in March, 2011. • Call will be led by faculty from the Integrative Medicine Program • Lorenzo Cohen, PhD • Kay Garcia, MSN, MPH, DrPH (acupuncturist) • Subcontracts will be implemented with participating sites to provide pass through funds for acupuncture. • Training videos will be provided for sites/acupuncturists

44. Cancer Control: Proposed 2011-0147(Not Yet Assigned)A Phase I Study of Sublingual Anvirzel (Nerium Oleander) in Advanced Non-Small Cell Lung Cancer Principal Investigator:Richard Lee, MD, MD Anderson Cancer Center Methodology: All subjects will receive SL Anvirzel dosing beginning 3 days prior to starting chemotherapy. A total of four dose cohorts will be evaluated (0.8, 1.6, 2.4, 3.2 ml/m2/day; SL q8hrs) with 7 patients per cohort. Protocol Status: NCI Concept Submission Pending Patient Population: Newly diagnosed advanced non-small cell lung cancer patients scheduled to receive four cycles of carboplatin and docetaxel chemotherapy. Total accrual goal of 28 patients.

45. Cancer Control: Proposed Not Yet Assigned Nano-curcumin in Breast Cancer Prevention in the Contralateral Breast Principal Investigator: Banu K. Arun, MD, MD Anderson Cancer Center Protocol Status: NCI Concept Submission Pending Patient Population: Breast Cancer Patients

46. Cancer Control: Proposed Not Yet AssignedBIG Study: Time Out for Reflection in the Course of Chemotherapy Principal Investigator:Jon Hunter, MD, Mount Sinai Hospital, Toronto, Michael J. Fisch, MD Anderson Cancer Center, Lorenzo Cohen, PhD, MD Anderson Cancer Center Protocol Status:NCI Concept Submission Pending Patient Population:Cancer Patients

47. CCOP Strategic Plan • Incoroporate emerging science and novel trial designs • Survivorship, tx toxicities, risk assessment • Use epi and biologic data from underrepresented populations • Improve clinical trial participation

48. Winning the future? • What are our biggest assets at MDACC? • What do we do best? • What should we do best (but aren’t yet)? • Creative ideas moving forward?

49. Thank Youmdaccop@mdanderson.org(713) 563-0276