LIVER DYSFUNCTION GROUPS Patients entering this study will be stratified into five groups or cohorts (A: normal, B: mild dysfunction, C: moderate dysfunction, D: severe dysfunction, E: liver transplant) according to their hepatic function as outlined in the following table: Group Liver Function Group A Group B Mild Group C Moderate Group D Severe Group E Liver Transplant Total Bilirubin ULN B1: ULN B2: >1.0x – 1.5x ULN >1.5x – 3x ULN >3x ULN Any SGOT/AST ULN B1: > ULN B2: Any Any Any Any INVESTIGATIONAL AGENT Please state route and schedule of Study Agent administration, and enter exact doses for each dose level and group in the table below. (For example, “Agent XXX is given intravenously as a 1-hour infusion on days 1, 3, and 5 of a 21-day cycle.) Study Agent is given (route/duration) on (day/days) of a (#)-day cycle. Group A Group B Group C Group D Group E Dose Level Normal liver function (units) * Mild liver dysfunction (units) * Moderate liver dysfunction (units) * Severe liver dysfunction (units) * Liver transplant (units) * Level -1 ** Level 1 ** Level 2 ** Level 3 ** Level 4 ** * Doses are stated as exact dose in units (e.g., mg/m2, mcg/kg, etc.) rather than as a percentage. ** (See Section 5.1.1 for the Group E dosing scheme.) Note: This schema is not to be used for determining dosage for any individual patient.
Expedited 24-hour notification followed by complete report within 5 calendar days for: All Grade 3, 4, and Grade 5 AEs Expedited 10 calendar reports for: Grade 2 AEs resulting in hospitalization or prolongation of hospitalization 2 For studies using PET or SPECT IND agents, the AE reporting period is limited to 10 radioactive half-lives, rounded UP to the nearest whole day, after the agent/intervention was last administered. Footnote “1” above applies after this reporting period. Effective Date: May 5, 2011 Additional Protocol-Specific Expedited Adverse Event Reporting Exclusions For this protocol only, the AEs/grades listed below do not require expedited reporting via AdEERS. However, they still must be reported through the routine reporting mechanism (Section 7.4): CTCAE SOC Adverse Event Grade Hospitalization/ Prolongation of Hospitalization Attribution Comments 7.4 Routine Adverse Event Reporting All Adverse Events must be reported in routine study data submissions. AEs reported through AdEERS must also be reported in routine study data submissions. 7.5 Secondary Malignancy A secondary malignancy is a cancer caused by treatment for a previous malignancy (e.g., treatment with investigational agent/intervention, radiation or chemotherapy). A secondary malignancy is not considered a metastasis of the initial neoplasm. CTEP requires all secondary malignancies that occur following treatment with an agent under an NCI IND/IDE be reported via AdEERS. Three options are available to describe the event: Leukemia secondary to oncology chemotherapy (e.g., acute myelocytic leukemia [AML]) Myelodysplastic syndrome (MDS) Treatment-related secondary malignancy Any malignancy possibly related to cancer treatment (including AML/MDS) should
Provide a hypothesis and rationale for biomarker utility and a description of the impact on therapeutic agent development based on the following considerations: Biological and/or mechanistic rationale with data to support relationship between biomarker and agent effects Intended use within the proposed study Preclinical in vitro and in vivo, and clinical results, if applicable Describe the assay method’s validity and appropriateness for the study Describe the investigator’s experience and competence with the proposed assays Provide the data supporting the degree of biomarker “fit for purpose” and clinical qualification Justify the number of patients and specimens: To demonstrate feasibility To demonstrate that studies are likely to produce interpretable and meaningful results Give thoughtful consideration to the risk to the patient of obtaining samples, specimens, or data for biomarker studies in the context of data on biomarker validity and degree of clinical qualification 9.3 Laboratory Correlative Studies 9.1.1 (Title – Laboratory Correlative Study #1) 9.1.1.1 Collection of Specimen(s) 9.1.1.2 Handling of Specimens(s) 9.1.1.3 Shipping of Specimen(s) 9.1.1.4 Site(s) Performing Correlative Study 9.1.2 (Title – Laboratory Correlative Study #2) 9.1.2.1 Collection of Specimen(s) 9.1.2.2 Handling of Specimens(s) 9.1.2.3 Shipping of Specimen(s) 9.1.2.4 Site(s) Performing Correlative Study 9.4 Special Studies 9.2.1 (Title – Special Correlative Study #1) 9.2.1.1 Outcome Measure 9.2.1.2 Assessment 9.2.1.2.1 Method of Assessment 9.2.1.2.2 Timing of Assessment 9.2.1.3 Data Recording 9.2.1.3.1 Method of Recording 9.2.1.3.2 Timing of Recording 10. STUDY CALENDAR Schedules shown in the Study Calendar below are provided as an example and should be modified as appropriate.
A Phase 1 and Pharmacokinetic Single Agent Study of Study Agent in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction Physician of record: Site Co-Investigator: NCI Investigator Number: NCI Investigator Number: Institution Name: Participating Site (Institution): NCI Site Code: NCI Site Code: Address: Address: Phone: ( ) Phone: ( ) Fax: ( ) Fax: ( ) E-mail: E-mail: ……Patient Initials (First, Middle, Last) …….Patient Date of Birth (mm/dd/yyyy) PATIENT DISEASE Primary Disease Site Stage of Disease Disease Grade Histology ELIGIBILITY CHECKLIST □ No □ Yes 1. Patient has a histologically or cytologically confirmed solid or hematologic malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. □ No □ Yes 2. Patient is > 18 years of age. □ No □ Yes 3. Life expectancy is greater than 3 months. □ No □ Yes 4. Patient’s performance status (ECOG scale) is < 2 (Karnofsky > 60%) □ No □ Yes 5. Patient has acceptable marrow and renal function as defined below: - ANC > 1.5 x 109/L platelet count > 100 x 109/L creatinine level within normal institutional limits OR creatinine clearance >60 mL/min/1.73 m2 if patient’s creatinine level is above institutional normal □ No □ Yes 6. Patient is free of unstable or untreated (non-irradiated) brain metastases. □ No □ Yes 7. Does patient have a history of allergic reactions to compounds of similar chemical or biologic composition to Study Agent.?_ □ No □ Yes 8. Does patient have any intercurrent illness including (but not limited to) the following: ongoing or active infection symptomatic congestive heart failure unstable angina pectoris cardiac arrhythmia psychiatric illness/social situations that would limit compliance with study requirements? □ No □ Yes 9. Is patient pregnant?