untitled h1
instructions to the patient

1. Complete one form for each Cycle.  
2. You will take ___ cabozantinib pills once each day. 3. Record the date, the number of pills you took, and when you took them.  
4. If you have any comments or notice any side effects, please record them in the Comments column. 5. Please bring your pill bottles and this form to your physician when you go for your next appointment.  
| 4.                                                                                                    | If you have any comments or notice any side effects, please record them in the Comments column.                     |                    |
|-------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------|--------------------|
| 5.                                                                                                    | Please bring your pill bottles and this form to your physician when you go for your next appointment.  Cabozantinib |                    |
| Date                                                                                                  | Day                                                                                                                 | (taken once a day) |
| # pills,                                                                                              | # pills                                                                                                             | Comments           |
| when taken                                                                                            | missed                                                                                                              |                    |
| 1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28 |                                                                                                                     |                    |
| Patient's Signature: ___________________________________ Date: ____________________                   |                                                                                                                     |                    |  
CTEP Study \#: 9236 Abbreviated Title: Ph 2 XL184 in urothelial CA
Version Date: 05/10/2019  
| 16.4 APPENDIX D: CCR PATIENT SELF-ADMINISTERED STUDY AGENT COMPLIANCE LOG   | This form is to be updated at every study contact where patient receives or returns study drug. This form may be used for multiple self-administered study agents.  This form is to be used in conjunction with a note in CRIS about study drug self-administration and case report form and will be maintained in the research record.  If patient is bringing back their study drug and you will not be returning that to the pharmacy, rather, the patient will be taking it back home with them, please use  the form entitled 'CCR Patient Self-Administered Study Agent Interim Compliance Form'.   | CC Protocol Number:_________________________                                                    | Site Staff  Initials  between actual and expected  amount returned, if  applicable  Reason for difference  Expected  Amount  Returned  Expected  Amount  Taken  Actual  Amount  Returned   |                |     |
|-----------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------|-----|
| Principal Investigator:______________________                               | Protocol Title:_____________________________________________________________________________                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | Patient's Medical Record Number:____________________ Patient's Name:___________________________ | Patient Study ID: ________________ Cycle Number_____                                                                                                                                       | Date Dispensed | 107 |
| ____                                                                        |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           |                                                                                                 |                                                                                                                                                                                            |                |     |
| /_____/20______                                                             | (mm/dd/yyyy)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | ____                                                                                            |                                                                                                                                                                                            |                |     |
| /_____/20______                                                             | (mm/dd/yyyy)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | ____                                                                                            |                                                                                                                                                                                            |                |     |
| /_____/20______                                                             | (mm/dd/yyyy)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | ____                                                                                            |                                                                                                                                                                                            |                |     |
| /_____/20______                                                             | (mm/dd/yyyy)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | ____                                                                                            |                                                                                                                                                                                            |                |     |
| /_____/20_____ ____/_____/20______                                          |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           |                                                                                                 |                                                                                                                                                                                            |                |     |
| Date Returned Dose Form                                                     | (e.g., tablets,  pills, bottles,  capsules, vials)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        |                                                                                                 |                                                                                                                                                                                            |                |     |
| Amount  Dispensed                                                           | ____                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      |                                                                                                 |                                                                                                                                                                                            |                |     |
| /_____/20_____                                                              | (mm/dd/yyyy)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | ____                                                                                            |                                                                                                                                                                                            |                |     |
| /_____/20_____                                                              | (mm/dd/yyyy)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | ____                                                                                            |                                                                                                                                                                                            |                |     |
| /_____/20_____                                                              | (mm/dd/yyyy)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | ____                                                                                            |                                                                                                                                                                                            |                |     |
| /_____/20_____                                                              | (mm/dd/yyyy)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              |                                                                                                 |                                                                                                                                                                                            |                |     |  
| Site Staff  Initials  between actual and expected  amount returned, if  applicable  Reason for difference  Expected  Amount  Returned  Expected  Amount  Taken  Actual  Amount  Returned   |                                                    |      |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------|------|
| CTEP Study #: 9236                                                                                                                                                                         | ____                                               |      |
| /_____/20______                                                                                                                                                                            | (mm/dd/yyyy)                                       | ____ |
| /_____/20______                                                                                                                                                                            | (mm/dd/yyyy)                                       |      |
| Date Returned                                                                                                                                                                              | (mm/dd/yyyy)                                       |      |
| Dose Form                                                                                                                                                                                  | (e.g., tablets,  pills, bottles,  capsules, vials) |      |
| Amount  Dispensed                                                                                                                                                                          |                                                    |      |
| Abbreviated Title: Ph 2 XL184 in urothelial CA Version Date: 05/10/2019                                                                                                                    | ____                                               |      |
| /_____/20_____                                                                                                                                                                             | (mm/dd/yyyy)                                       | ____ |
| /_____/20_____                                                                                                                                                                             | (mm/dd/yyyy)                                       |      |
| Date Dispensed                                                                                                                                                                             | (mm/dd/yyyy)                                       |      |
untitled h1
16.5 appendix e blood pressure

For use in patients with a history of hypertension  
| Instructions  1. Take your blood pressure once per week during each cycle of cabozantinib  2. Record the date you took your blood pressure and your blood pressure below 3. Bring this form with you at your next study visit Week Date Blood Pressure  1 /  2 /  3 /  4 /   |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| 16.6                                                                                                                                        | APPENDIX F: SAMPLE COLLECTION FOR CORRELATIVE STUDIES                                                                     |                                                                                         |                    |         |
|---------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------|--------------------|---------|
| Test                                                                                                                                        | Amount/Type/T                                                                                                             | Collection  Timing                                                                      | Contact            | Special |
| description                                                                                                                                 | ube/Handling                                                                                                              | Instructions                                                                            |                    |         |
| Please email  NCIBloodcore@mail.nih.gov  24 hours prior to anticipated  collection and page 102-11964  for pickup.                          |                                                                                                                           |                                                                                         |                    |         |
| At any time after  consent is signed,  but preferably at  baseline                                                                          |                                                                                                                           |                                                                                         |                    |         |
| Oragene saliva                                                                                                                              |                                                                                                                           |                                                                                         |                    |         |
| Saliva                                                                                                                                      | collection kits  (DNA Genotek)                                                                                            | store at room temp                                                                      |                    |         |
| When scheduled email Jane  Trepel (trepel@helix.nih.gov),  Sunmin Lee  (lees@pop.nci.gov), Mi-Jung  (leemin@mail.nih.gov, and  Maria Merino | Analyzed by  immunohistochemi stry and flow  cytometry as  appropriate                                                    |                                                                                         |                    |         |
| 4-6 cores, Tumor  block, 10 unstained  slides, or a fresh  tumor biopsy                                                                     |                                                                                                                           |                                                                                         |                    |         |
| Met expression  in tissue                                                                                                                   | Pre-treatment                                                                                                             | When patient arrives at IR call                                                         |                    |         |
|                                                                                                                                             | Jane Trepel (240) 760-6330  and Maria Merino                                                                              | Tissue biopsies  strictly on  voluntary basis                                           |                    |         |
| HTG Molecular Diagnostics,  Inc. 3430 E. Global Loop Tucson, AZ 85706 T: (877) 289-2615  F: (520) 547-2837                                  |                                                                                                                           |                                                                                         |                    |         |
| HTG EdgeSeq  ImmunoOncology and  OBP Assays                                                                                                                                             | H&E and serial  unstained slides                                                                                          |                                                                                         |                    |         |
| Two 10cc Lavender  top EDTA tube Three 8mL bluetiger top BD  Vacutainer  Preparation tube  with sodium citrate                                                                                                                                             | When scheduled email Jane  Trepel (trepel@helix.nih.gov),  Sunmin Lee  (lees@pop.nci.gov), Mi-Jung  (leemin@mail.nih.gov) | Gently invert  sample several  times immediately  after collection,  store at room temp |                    |         |
| CEC, CEP, and  CTC                                                                                                                          | Pre-treatment                                                                                                             | When drawn call Trepel lab                                                              |                    |         |
| Date and Time tube                                                                                                                          | C3D1                                                                                                                      | (240) 760-6330 for immediate                                                            |                    |         |
| pick up When scheduled email Jane  Trepel (trepel@helix.nih.gov),  Sunmin Lee  (lees@pop.nci.gov), Mi-Jung  (leemin@mail.nih.gov)           | invert several  times and place at  room temp or  refrigerate                                                             |                                                                                         |                    |         |
| C-Met analysis  by real-time  RT-PCR                                                                                                        | PAXgene tube  (PreAnalytix; 2.5cc                                                                                         | Pre-treatment                                                                           |                    |         |
| blood per tube)                                                                                                                             | When drawn call Trepel lab                                                                                                |                                                                                         |                    |         |
| Date and Time tube                                                                                                                          | C3D1                                                                                                                      | (240) 760-6330 for immediate  pick up When scheduled, email Jane  Trepel (trepel@helix.nih.gov),  Sunmin Lee  (lees@pop.nci.nih.gov), MinJung Lee  (leemin@mail.nih.gov)                                                                                         |                    |         |
| IL-8 circulating                                                                                                                            | One 5mL red top                                                                                                           | C1D1, C1D15,                                                                            |                    |         |
| cytokine levels                                                                                                                             | tube                                                                                                                      | C2D1                                                                                    | store at room temp |         |  
| Version Date: 05/10/2019  Test  Amount/Type/T                                                                                               | Collection  Timing                                                                                                   | Contact                                                                                                                               | Special                                                                                                                                           |
|---------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------|
| description                                                                                                                                 | ube/Handling                                                                                                         | Instructions                                                                                                                          |                                                                                                                                                   |
| When drawn call (240) 760- 6330 (Trepel lab) for                                                                                            |                                                                                                                      |                                                                                                                                       |                                                                                                                                                   |
| immediate pick up                                                                                                                           |                                                                                                                      |                                                                                                                                       |                                                                                                                                                   |
| Date and Time tube                                                                                                                          | Invert 8-10 times,  place on wet ice  and store at 4°C in  refrigerator until  procession                            |                                                                                                                                       |                                                                                                                                                   |
| Genetic                                                                                                                                     |                                                                                                                      |                                                                                                                                       |                                                                                                                                                   |
| biomarkers  (VEGFR2)                                                                                                                        | One 10mL EDTA  lavender top tube                                                                                     | C2D1                                                                                                                                  | e-mail 24 hr prior, Please page  102-11964 - Figg lab                                                                                             |
| Date and Time tube                                                                                                                          |                                                                                                                      | Invert EDTA tube  2-4 times, place on  wet ice and store at  4°C in the  refrigerator until  processing for a  maximum of 30-60  min. |                                                                                                                                                   |
| C1D1, C1D15,                                                                                                                                |                                                                                                                      |                                                                                                                                       |                                                                                                                                                   |
| Angiogenesis  markers                                                                                                                       | 4mL EDTA tube                                                                                                        | C2D1,  progression                                                                                                                    | E-mail 24hr prior, Please page  102-11964 - Figg lab                                                                                              |
| Date and Time tube                                                                                                                          | Should be  centrifuged within  30 min                                                                                |                                                                                                                                       |                                                                                                                                                   |
| Plasma HGF                                                                                                                                  | One 3mL EDTA                                                                                                         | prior to treatment,                                                                                                                   | Email 24 hr prior, Please page                                                                                                                    |
| and MET                                                                                                                                     | tube                                                                                                                 | every visit                                                                                                                           | 102-11964 - Figg lab                                                                                                                              |
| Date and Time tube                                                                                                                          | Refrigerate  samples The interval  between sample  acquisition and  freezing on dry ice  must not exceed 2  minutes. |                                                                                                                                       |                                                                                                                                                   |
| When scheduled, contact Dr.  Bottaro to notify of biopsy  date and time (301-402-6499)  and to arrange for pick up of  sample during biopsy |                                                                                                                      |                                                                                                                                       |                                                                                                                                                   |
| Analysis of                                                                                                                                 |                                                                                                                      |                                                                                                                                       |                                                                                                                                                   |
| tissue HGF and  cabozantinib  targets                                                                                                       | 4-6 cores of fresh                                                                                                   | x                                                                                                                                     | Pre-treatment                                                                                                                                     |
| tumor biopsy                                                                                                                                | x                                                                                                                    | 8 - 18 weeks                                                                                                                          | Tissue biopsies  strictly on  voluntary basis  Note urine source:  void, percutaneous  stent, Foley,  neobladder, Indian  pouch, or ileal conduit |
| Urinary MET  and urine spot  creatinine                                                                                                     | Collect at least 2mL                                                                                                 | prior to treatment,                                                                                                                   | Email 24 hr prior, Please page                                                                                                                    |
| of urine                                                                                                                                    | every visit                                                                                                          | 102-11964 - Figg lab                                                                                                                  |                                                                                                                                                   |  
| Test                                                  | Amount/Type/T                                                                                                                                | Collection  Timing                                                                                        | Contact   | Special   |
|-------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------|-----------|-----------|
| description                                           | ube/Handling                                                                                                                                 | Instructions                                                                                              |           |           |
| Date, Time and  source of urine on                    |                                                                                                                                              |                                                                                                           |           |           |
| tube                                                  | When scheduled email Jane  Trepel (trepel@helix.nih.gov),  Sunmin Lee  (lees@pop.nci.gov), Mi-Jung  (leemin@mail.nih.gov), and  Maria Merino |                                                                                                           |           |           |
| Immune subsets  and  angiogenesis  markers in  tissue | Tissue biopsies  strictly on  voluntary basis                                                                                                |                                                                                                           |           |           |
| 4-6 cores of fresh                                    | 8-18 weeks post                                                                                                                              |                                                                                                           |           |           |
| tumor biopsy                                          | treatment                                                                                                                                    | Nagireddy Putluri, Ph.D  Associate Professor  120D, Jewish Building One Baylor Plaza, Houston,  TX, 77030 |           |           |
| Xenobiotic  Metabolism                                | 100 ul of plasma                                                                                                                             | Eppendorf tube                                                                                            |           |           |
untitled h1
m. d. anderson symptom inventory

Part I. How severe are your symptoms?  
People with cancer frequently have symptoms that are caused by their disease or by their treatment. We ask you to rate how severe the following symptoms have been in the last 24 hours. Please fill in the circle below from 0
(symptom has not been present) to 10 (the symptom was as bad as you can imagine it could be) for each item.  
| Not                              |                                    |    |    |    |    |
|----------------------------------|------------------------------------|----|----|----|----|
| Present                          |                                    |    |    |    |    |
| 0                                | 1                                  | 2  | 3  |    |    |
| 1.                               | Your pain at its WORST?            | o  | o  | o  | O  |
| 2.                               | Your fatigue (tiredness) at        | o  | o  | o  | O  |
| its WORST?                       |                                    |    |    |    |    |
| 3.                               | Your nausea at its WORST?          | o  | o  | o  | o  |
| 4.                               | Your disturbed sleep at its        | o  | o  | o  | o  |
| WORST?                           |                                    |    |    |    |    |
| 5.                               | Your feelings of being             | o  | o  | o  | O  |
| distressed (upset) at its WORST? |                                    |    |    |    |    |
| 6.                               | Your shortness of breath at its    | o  | o  | o  | o  |
| WORST?                           |                                    |    |    |    |    |
| 7.                               | Your problem with remembering      | o  | o  | o  | O  |
| things at its WORST?             |                                    |    |    |    |    |
| a'                               | Your problem with lack of appetite | O  | o  | o  | o  |
| at its WORST?                    |                                    |    |    |    |    |  
| 4   | 5   | 6   |
|-----|-----|-----|
| o   | o   | O   |
| o   | O   | o   |
| o   | o   | o   |
| O   | o   | o   |
| o   | o   | O   |
| O   | o   | O   |
| O   | O   | o   |
| O   | O   | o   |  
| As Bad As You   |    |    |    |
|-----------------|----|----|----|
| Can Imagine     |    |    |    |
| 7               | 8  | 9  | 10 |
| O               | O  | O  | o  |
| o               | o  | o  | o  |
| o               | o  | o  | o  |
| o               | o  | o  | o  |
| o               | o  | O  | o  |
| o               | o  | o  | o  |
| O               | O  | O  | O  |
| O               | o  | o  | o  |
| O               | O  | O  | O  |  
  
  
Copyright 1999 The University of Texas M. D. Anderson Cancer Center All rights reserved  
  
| 3   | 4   |
|-----|-----|
| o   | O   |
| o   | o   |
| o   | o   |
| o   | o   |
| O   | o   |
| O   | O   |  
  
   
  
| Not                               |    |    |    |    |    |    |    |    |    |
|-----------------------------------|----|----|----|----|----|----|----|----|----|
| Present                           |    |    |    |    |    |    |    |    |    |
| o                                 | 1  | 2  | 3  | 4  | 5  | 6  | 7  | 8  |    |
| 1. Your feeling sad at its WORST? | O  | o  | o  | o  | O  | o  | o  | o  | o  |
| 12. Your vomiting at its WORST?   | o  | o  | o  | o  | o  | o  | o  | o  | o  |
| 13. Your numbness or tingling at  | O  | o  | o  | o  | o  | o  | o  | o  | o  |
| its WORST?                        |    |    |    |    |    |    |    |    |    |  
| As Bad As You   |    |
|-----------------|----|
| Can Imagine     |    |
| 9               | 10 |
| o               | o  |
| o               | o  |
| o               | o  |  
Part II. How have your symptoms interfered with your life?  
Symptoms frequently interfere with how we feel and function. How much have your symptoms interfered with the following items in the last 24 hours:  
| Did Not                          |    |    |    |
|----------------------------------|----|----|----|
| Interfere                        |    |    |    |
| 0                                | 1  | 2  |    |
| 14. General activity?            | o  | O  | o  |
| 15. Mood?                        | o  | o  | O  |
| 16.  Work (including work around | O  | O  | o  |
| the house)?                      |    |    |    |
| 17. Relations with other people? | o  | o  | o  |
| 18. Walking?                     | o  | O  | O  |
| 19. Enjoyment of life?           | o  | O  | o  |  
Copyright 1999 The University of Texas M. D. Anderson Cancer Center  
| Interefered
Completely    |    |
|----|----|
| 10 |    |
| 9  |    |
| o  | o  |
| O  | o  |
| O  | O  |
| o  | o  |
| o  | O  |
| o  | o  |  
All rights reserved  
| 5   | 7   | 8   |    |
|-----|-----|-----|----|
| 6   |     |     |    |
| o   | O   | o   | O  |
| o   | o   | o   | o  |
| o   | o   | O   | o  |
| o   | o   | o   | o  |
| O   | O   | O   | O  |
| O   |     |     |    |
| o   | o   | o   |    |