Ana Luisa Stuckett, PhD, MS

Transcription

1 Ana Luisa Stuckett, PhD, MS Clinical Studies Coordinator Investigational Cancer Therapeutics (Phase I) MD Anderson Cancer Center Houston, Texas

2 Education Ph.D., Microbiology, 2009 University College of Cork, Ireland M.S., Food Biotechnology, 2004 The University of Reading, U.K. B.S., Agro-Industrial Engineering, 2003 Technical University of Lisbon, Portugal

3 Professional Experience Clinical Studies Coordinator 02/ present Investigational Cancer Therapeutics (Phase I), The University of Texas, M.D. Anderson Cancer Center, Houston, TX Adjunct faculty 06/ present Lee College, Baytown, TX Postdoctoral Research Associate 09/ /2016 Laboratories of Drs. Magnus Hook and Julian Hurdle, Texas A&M University HSC, Houston, TX Postdoctoral Research Associate 09/ /2010 Laboratory of Dr. Barbara Murray, University of Texas Health Science Center at Houston (UT Health), Houston, TX Doctoral Candidate 09/ /2009 Laboratory of Dr. E. Fidelma Boyd, University of Delaware, Newark, DE,

4 Investigational Cancer Therapeutics

5 Oncology Clinical trials Phase I Phase II determines whether the drug is safe to check for efficacy patients determines whether drug can have any efficacy; at this point, the drug is not presumed to have any therapeutic effect whatsoever Phase III patients with specific diseases determines a drug's therapeutic effect; at this point, the drug is presumed to have some effect Phase IV 300-3,000 patients with specific diseases Post-marketing surveillance; watch drug's long-term effects

6 Phase I Oncology Clinical trials First-in-man This phase is designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of a drug. Dose escalation: typically design Phase Ia (single ascending dose study) Phase Ib (multiple ascending dose study) Food effect

7 Phase II Oncology Clinical trials: dose expansion

8 Sponsor trials: order of events Protocol is presented to the Principal Investigator; reviewed and approved by the IRB Site Initiation Visit (SIV) at the site (sponsor, monitor team, PI, SC, pharmacy required to be present) Protocol is opened (Study site is given a certain number of slots; rules are defined by the sponsor and it is study dependent). Patients are pre-screened; financial clearance requested Patient consents to the study; does screening procedures, clearance visit; initiates the study drug; patient is monitored intensely during Cycle 1 (DLT window); decreases over time. Disease is assessed by scans every 2 drug cycles

9 Example of inclusion criteria Patients 18 years of age. Histologically or cytologically confirmed diagnosis of solid malignancy, for which no standard curative or life prolonging therapy is available. Have an ECOG Performance Status of 1. Life expectancy of 12 weeks. Adequate bone marrow, liver, and renal functions, defined as: Platelet count 100 x 10 9 /L absolute neutrophil count (ANC) 1.5 x 10 9 /L hemoglobin 9 g/dl, ALT and AST 2.5 upper limit normal (ULN) i.e. ALT 140, AST 115, or < 5 x ULN if liver metastases are present, i.e ALT 280, AST 230 serum total bilirubin ULN, i.e.1.3mg/dl or 1.5 x ULN if liver metastases are present, i.e mg/dl or total 3 x ULN with direct bilirubin ULN in patients with well documented Gilbert Syndrome, i.e. 3.9mg/dl. Serum Creatinine < 1.5 x ULN, i.e. 1 mg/dl for women; 1.95 mg/dl for men or estimated creatinine clearance 60 ml/min, as calculated using method standard for the institution. HgbA1c 7%, Fasting Plasma Glucose (FPG) 7.0 mmol/l (125 mg/dl). Women of childbearing potential must have a negative pregnancy test (urine or serum) performed within 7 days prior to the start of study drug. Able and willing to swallow and retain oral medication.

10 Example of exclusion criteria Concurrent or previous anti-cancer chemotherapy, immunotherapy or investigational agents < 3 weeks, or palliative radiation < 2 weeks prior to the first day of study treatment. Patients who receive gamma knife radiosurgery for brain metastases or whole brain radiation are eligible if gamma knife radiosurgery was performed > 2 weeks before treatment is started or whole brain radiation was performed > 4 weeks before treatment is started, and are clinically stable. Hormonal anticancer therapies except for LHRH antagonists or LHRH agonists in hormone-refractory prostate cancer. Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects. Patients who are on (or will require) prolonged systemic corticosteroid treatment during the study, except for: if receiving corticosteroids, patients must have been on a stable or decreasing dose of corticosteroids and no more than 1 mg of dexamethasone a day or equivalent, i.e. 6 mg prednisone or 25 mg hydrocortisone for at least 5 days prior to date of enrollment; a short duration (< 5 days) of systemic corticosteroids e.g., of chronic obstructive pulmonary disease, or as an antiemetic corresponding at maximum to the anti-inflammatory potency of 4 mg dexamethasone for treatment; topical applications for treatment of e.g., rash, inhaled sprays for treatment of e.g., obstructive airways diseases, eye drops or local injections (e.g., intra-articular)

11 Example of exclusion criteria Patient has a known history of HIV infection (testing not mandatory). Patient has Left Ventricular Ejection Fraction (LVEF) < 40% as determined by Multiple Gated Acquisition (MUGA) scan or echocardiogram (ECHO). Concomitant treatment with medicinal products that increase the ph (reduce acidity) of the upper gastrointestinal tract, including, but not limited to, protonpump inhibitors (e.g. omeprazole), H2-antagonists (e.g. ranitidine) and antacids. Patients may be enrolled in the study after a wash-out period sufficient to terminate their effect. Patients have any of the following mood disorders as judged by the Investigator or a psychiatrist, or who meets the cut-off score of 12 the PHQ-9 or a cut-off of 15 in the GAD-7 mood scale, respectively, or selects a positive response of 1, 2, or 3 to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9); Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others); CTCAE Grade 3 anxiety. Patients with a history of interstitial pneumonitis or patients who require chronic oxygen supplementation

12 The role: clinical studies coordinator Responsible for screening and verifying patients eligibility for clinical trial protocols based on molecular profiling, tumor types and subjects performance status. Serves as a liaison to patients, physicians, mid-level providers, clinical nurses, principal investigators, pharmaceutical companies, study monitors, regulatory entities and others. Provides independent and advance clinical and operational management of multiple research protocols

13 Other duties of the Study Coordinator Schedule appointments within protocol window Study notes Document Adverse Events/Severe adverse events Support monitoring visits/audits Report deviation and/or violation/keep a log Report patient information to the sponsor and monitoring team at the teleconferences Follow up on patient reimbursements Update sponsor s database Create continuing review

14 Management of Adverse Events

15 Management of Adverse Events

16 Career options Clinical Project Manager Clinical Research Program Coordinator Clinical Research Associate (CRA) (aka study monitor) Clinical Scientist Program Manager Scientific Manager Medical Science Liaison (MSL)