Dose-Escalation Scheme (Renal Dysfunction) 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.) [CTEP IND is given [route/duration] on [day/days] of a [#]-day cycle. Group A Group B Group C Group D Group E Dose Level Normal function (units) * Mild renal dysfunction (units) * Moderate renal dysfunction (units) * Severe renal dysfunction (units) * Kidney dialysis (units) * Level -1 TBD** *** 1 TBD** *** Level 2 TBD** *** 3 TBD** *** Level 4 TBD** *** * are stated as exact dose in clinically utilized units (e.g., mg/m2, mcg/kg, etc.) rather than as a percentage. ** To be determined on the safety data available for Normal and Moderate at the time that this group potentially would be activated for enrollment Section 6.2 for the E dosing scheme. See Section 6.2 for definitions of dysfunction groups. The cohort of patients will be treated at dose level 1. Dose level –1 is only to be used if dose reduction is necessary. The following modifications to the usual “3&3” dose escalation scheme allow for the dosing of new patients in the event that not all patients treated at a current dose level are yet evaluable for toxicity. Dose Escalation Rules Dose escalation will proceed within each renal dysfunction group according to the scheme outlined in Section 6.6. DLT is defined above (Section 6.4). Only DLTs that during the first cycle of treatment will be used to guide dose escalation. Patients are considered evaluable for toxicity when they have received the planned dose or duration of therapy and have either 1) experienced DLT or 2) been followed for one full without DLT. Dose Escalation Definitions
The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. For Patients with Measurable Disease (i.e., Target Disease) Target Lesions Non-Target Lesions New Lesions Overall Response Best Overall Response when Confirmation is Required* CR CR No CR >4 wks. Confirmation** CR No PR >4 wks. Confirmation** CR Not evaluated No PR PR evaluated No PR SD evaluated No SD Documented at least once >4 wks. from baseline** PD Any Yes or No PD no SD, PR or CR Any PD*** Yes or No PD Any Any Yes PD See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. ** Only for non-randomized trials with response as primary endpoint. *** In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as disease progression. Note: Patients with a global deterioration of health status requiring discontinuation of treatment without objective evidence of disease progression at that time should be reported as “symptomatic deterioration.” effort should be made to document the objective progression even after discontinuation of treatment. For Patients with Non-Measurable Disease (i.e., Non-Target Disease) Non-Target Lesions New Lesions Overall Response CR No CR Non-CR/non-PD No Non-CR/non-PD* Not all evaluated No not evaluated Unequivocal PD Yes or No PD Any Yes PD ‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is increasingly used as an endpoint for assessment of efficacy in some trials so to assign this category when no lesions can be measured is not advised
Duration of Response Duration of overall response: The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented. Duration of stable disease: Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements. Progression-Free Survival Include this section if time to progression or progression-free survival (PFS) is to be used. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Response Review For trials where the response rate is the primary endpoint, it is strongly recommended that all responses be reviewed by an expert(s) independent of the study at the study’s completion. Simultaneous review of the patients’ files and radiological images is the best approach. Antitumor Effect – Hematologic Tumors Please provide appropriate criteria for evaluation of response and methods of measurement. Add subsections as needed. Other Response Parameters Other endpoints and the criteria for their measurement should be entered below or reference should be made to the protocol section where these criteria may be found. Add subsections as needed. STUDY OVERSIGHT AND DATA REPORTING / REGULATORY REQUIREMENTS Adverse event lists, guidelines, and instructions for AE reporting can be found in Section 10 (Adverse Events: List and Reporting Requirements). Study Oversight
Patient’s Initial Consent given for specimen use for research on the patient's cancer? Yes No Patient’s Initial Consent given for specimen use for research unrelated to the patient's cancer? Yes No Patient’s Initial Consent given for further contact regarding specimen? Yes No Date of Consent for Specimen Use MM DD YYYY APPENDIX F PATIENT DRUG INTERACTIONS HANDOUT AND WALLET CARD Instructions for Patient drug interactions handout and wallet card Template Patient Drug Interactions Handout and Wallet Card is a requirement that must meet CTEP Policies & Procedures for non-marketed investigational agents. The instructions below specify which template to use. Please note the drug interactions handout and wallet card require IRB approval before distribution to patients. Instructions to authors: to the table below to determine which template (Template A or Template B) you should use and fill out the appropriate information as instructed by the template. Use or delete sections below as appropriate. Only edit the fillable text fields – do not alter any text outside of the fillable fields. The bracketed instruction text will disappear once you begin typing. Template A: Patient Drug Interactions Handout and a Patient Drug Interactions Wallet Card To be given at the time of enrollment and when updated. A protocol that has more than one non-marketed investigational agent with PK interactions will have a drug interactions handout and drug interactions wallet card for each agent. Assign a letter or a numeral to the Appendix. A convenient wallet-sized information card for the patient to cut out and retain at all times. Suggested texts to complete the templates are on the next page. Use the fillable template and enter information in the fillable fields. Template B: Patient Clinical Wallet Card only To be given to the patient at the time of enrollment. A convenient wallet-sized information card for the patient to cut out and retain at all times. Assign a letter or a numeral to the Appendix. Suggested to complete the template are on the next page. Use the fillable template and information in the fillable fields. When the Patient Drug Interactions Handout and Wallet Card is required and who is responsible for the authorship is summarized in below:
very important to tell your doctors about all your medicines, including: (a) medicines you are taking before this clinical trial, (b) medicines you start or stop taking during this study, (c) medicines you buy without a prescription (over-the-counter remedy), (d) herbals or supplements (e.g. St. John’s Wort). It is helpful to bring your medication bottles or an updated medication list with you. Before you enroll onto the clinical trial, your study doctor will work with your regular health care providers to review any medicines and herbal supplements that are considered Please be very careful! Over-the-counter drugs (including herbal supplements) may contain ingredients that could interact with your study drug. Speak to your doctors or pharmacist to determine if there could be any side effects. Make sure your doctor knows to avoid certain prescription medications. Your regular health care provider should check a frequently updated medical reference or call your study doctor before prescribing any new medicine or discontinuing any medicine. Version (Next page: Patient Drug Interaction Wallet Card)