untitled h1
12 appendices

| 12.1                                                                                                                                                                                       | APPENDIX A: PERFORMANCE STATUS CRITERIA ECOG Performance Status Scale   | Karnofsky Performance Scale                                  |             |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------|--------------------------------------------------------------|-------------|
| Grade                                                                                                                                                                                      | Descriptions                                                            | Percent                                                      | Description |
| 100                                                                                                                                                                                        | Normal, no complaints, no  evidence of disease.                         |                                                              |             |
| Normal activity. Fully active,                                                                                                                                                             |                                                                         |                                                              |             |
| 0                                                                                                                                                                                          | able to carry on all pre-disease  performance without restriction.      | Able to carry on normal activity;                            |             |
| 90                                                                                                                                                                                         | minor signs or symptoms of  disease. Normal activity with effort;       |                                                              |             |
| 80                                                                                                                                                                                         | some signs or symptoms of  disease.                                     |                                                              |             |
| Symptoms, but ambulatory.  Restricted in physically strenuous  activity, but ambulatory and able  to carry out work of a light or  sedentary nature (e.g., light  housework, office work). |                                                                         |                                                              |             |
| 1                                                                                                                                                                                          | Cares for self, unable to carry on                                      |                                                              |             |
| 70                                                                                                                                                                                         | normal activity or to do active  work.                                  |                                                              |             |
| In bed <50% of the time.  Ambulatory and capable of all  self-care, but unable to carry out  any work activities. Up and  about more than 50% of waking  hours.                            | Requires occasional assistance,                                         |                                                              |             |
| 60                                                                                                                                                                                         | but is able to care for most of  his/her needs.                         |                                                              |             |
| 2                                                                                                                                                                                          | 50                                                                      | Requires considerable assistance  and frequent medical care. |             |
| 40                                                                                                                                                                                         | Disabled, requires special care  and assistance.                        |                                                              |             |
| In bed >50% of the time.  Capable of only limited self-care,  confined to bed or chair more  than 50% of waking hours.                                                                     |                                                                         |                                                              |             |
| 3                                                                                                                                                                                          | Severely disabled,                                                      |                                                              |             |
| 30                                                                                                                                                                                         | hospitalization indicated. Death  not imminent.                         |                                                              |             |
| 20                                                                                                                                                                                         | Very sick, hospitalization  indicated. Death not imminent.              |                                                              |             |
| 100% bedridden. Completely  disabled. Cannot carry on any  self-care. Totally confined to bed  or chair.                                                                                   |                                                                         |                                                              |             |
| 4                                                                                                                                                                                          | 10                                                                      | Moribund, fatal processes  progressing rapidly.              |             |
| 5                                                                                                                                                                                          | Dead.                                                                   | 0                                                            | Dead.       |  
Version Date: March 21, 2019  
| 12.2                                                 | APPENDIX B: COXEN DRUG INDEX WITH FDA-APPROVED DOSE AND SCHEDULE Formulary  Status Drug Name and                                                                                              |                                                           |                                           |                                                                             |
|------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------|-------------------------------------------|-----------------------------------------------------------------------------|
| #                                                    | route of                                                                                                                                                                                      |                                                           |                                           |                                                                             |
| administration                                       | FDA-Approved                                                                                                                                                                                  | FDA-Approved Dose &                                       |                                           |                                                                             |
| Indication                                           | Schedule                                                                                                                                                                                      |                                                           |                                           |                                                                             |
| (Y, yes; N,  no)                                     |                                                                                                                                                                                               |                                                           |                                           |                                                                             |
| Abiraterone                                          |                                                                                                                                                                                               |                                                           |                                           |                                                                             |
| 1                                                    | N                                                                                                                                                                                             | mCRPC                                                     | 1000mg QDay w/ prednisone                 |                                                                             |
| (PO)                                                 | Induction: 0.15 mg/kg/day until bone  marrow remission, max 60 induction  doses Consolidation: 0.15 mg/kg/day  starting 3-6 weeks after completion  of induction, max 25 consolidation  doses |                                                           |                                           |                                                                             |
| Arsenic Trioxide                                     | N                                                                                                                                                                                             | APL, relapsed or                                          |                                           |                                                                             |
| 2                                                    | refractory                                                                                                                                                                                    |                                                           |                                           |                                                                             |
| (IV) Asparaginase,  Escherichia coli source (IV, IM) |                                                                                                                                                                                               |                                                           |                                           |                                                                             |
| 3                                                    | Y                                                                                                                                                                                             | ALL                                                       | 6000 units/m2 /dose TIW  Initial: 5mg BID |                                                                             |
| Axitinib                                             |                                                                                                                                                                                               |                                                           |                                           |                                                                             |
| 4                                                    | N                                                                                                                                                                                             | RCC, advanced                                             |                                           |                                                                             |
| (PO)                                                 | Dose Increases: If tolerance criteria  are met (see package insert), dose  may be increased to 7mg BID then to  10mg BID Initial Cycle: 75mg/m2 /day x 7days                                  |                                                           |                                           |                                                                             |
| Azacitidine                                          |                                                                                                                                                                                               |                                                           |                                           |                                                                             |
| 5                                                    | Y                                                                                                                                                                                             | MDS                                                       |                                           |                                                                             |
| (IV, SubQ)                                           | Subsequent Cycles: 75 mg/m2 /day x  7 days Q4weeks Dose Increases: may increase to  100mg/m2 /day after 2 cycles                                                                              |                                                           |                                           |                                                                             |
| CLL                                                  | 100mg/m2 on days 1 and 2 of a 28- day cycle, max 6 cycles                                                                                                                                     |                                                           |                                           |                                                                             |
| Bendamustine                                         |                                                                                                                                                                                               |                                                           |                                           |                                                                             |
| 6                                                    | Y                                                                                                                                                                                             |                                                           |                                           |                                                                             |
| (IV)                                                 | NHL                                                                                                                                                                                           | 120mg/m2 on days 1 and 2 of a 21- day cycle, max 8 cycles |                                           |                                                                             |
| Squamous Cell                                        | 0.25-0.5units/kg Qweek or BIW                                                                                                                                                                 |                                                           |                                           |                                                                             |
| Bleomycin                                            |                                                                                                                                                                                               |                                                           |                                           |                                                                             |
| 7                                                    | Y                                                                                                                                                                                             |                                                           |                                           |                                                                             |
| (IV, IM, SubQ)                                       | Note: Lymphoma patients should be                                                                                                                                                             |                                                           |                                           |                                                                             |
| Lymphomas                                            | treated with ≤ 2 units for the first two  doses                                                                                                                                               |                                                           |                                           |                                                                             |
| Testicular                                           |                                                                                                                                                                                               |                                                           |                                           |                                                                             |
| 8                                                    | Bortezomib                                                                                                                                                                                    | Y                                                         | MM,                                       | 1.3mg/m2 days 1, 4, 8, 11, 22, 25, 29,  and 32 of a 42-day cycle x 4 cycles |  
| Version Date: March 21, 2019   | Formulary  Status                                                                                                                                  |                                                                                                |                           |                                |
|--------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------|---------------------------|--------------------------------|
| Drug Name and                  |                                                                                                                                                    |                                                                                                |                           |                                |
| #                              | route of                                                                                                                                           |                                                                                                |                           |                                |
| administration                 | FDA-Approved                                                                                                                                       | FDA-Approved Dose &                                                                            |                           |                                |
| Indication                     | Schedule                                                                                                                                           |                                                                                                |                           |                                |
| (Y, yes; N,  no)               |                                                                                                                                                    |                                                                                                |                           |                                |
| (IV, SubQ)                     | first-line                                                                                                                                         | THEN 1.3mg/m2  days 1, 8, 22 and  29 of a 42-day cycle x 5 cycles  w/ melphalan and prednisone |                           |                                |
| MM, relapsed                   | 1.3mg/m2 days 1, 4, 8, and 11 of a                                                                                                                 |                                                                                                |                           |                                |
| Mantle Cell                    | 21-day cycle                                                                                                                                       |                                                                                                |                           |                                |
| Lymphoma                       |                                                                                                                                                    |                                                                                                |                           |                                |
| Busulfan                       |                                                                                                                                                    |                                                                                                |                           |                                |
| 9                              | (PO)                                                                                                                                               | N                                                                                              | CML, palliation           | 60mcg/kg/day or 1.8 mg/m2 /day |
| Busulfan                       | Y                                                                                                                                                  | HSCT conditioning  regimen                                                                     | 0.8mg/kg Q6hours x 4 days |                                |
| (IV)                           | Ovarian, advanced                                                                                                                                  | AUC 4-6 Q4weeks                                                                                |                           |                                |
| 10                             | Carboplatin                                                                                                                                        | Y                                                                                              |                           |                                |
| (IV)                           | AUC 5 Q3weeks w/gemcitabine and  paclitaxel OR AUC 5 Q3weeks w/ gemcitabine OR  AUC 6 Q3weeks w/ paclitaxel                                        |                                                                                                |                           |                                |
| Bladder (unlabeled use)        | Cycle 1: 20mg/m2 on days 1, 2, 8, 9,  15, and 16 of a 28-day cycle  Subsequent Cycles: 27mg/m2  on  days 1, 2, 8, 9, 15, and 16 of a 28-day  cycle |                                                                                                |                           |                                |
| Carfilzomib                    | MM, relapsed or                                                                                                                                    |                                                                                                |                           |                                |
| 11                             | N                                                                                                                                                  |                                                                                                |                           |                                |
| (IV)                           | refractory Brain Tumors Hodgkin's  Lymphoma                                                                                                        | 75-100mg/m2 /day x 2 days Q6weeks                                                              |                           |                                |
| Carmustine                     |                                                                                                                                                    |                                                                                                |                           |                                |
| 12                             | Y                                                                                                                                                  |                                                                                                |                           |                                |
| (IV)                           | 150-200mg/m2  Q6weeks OR                                                                                                                           |                                                                                                |                           |                                |
| MM NHL CLL                     | 0.1mg/kg/day x 3-6 weeks                                                                                                                           |                                                                                                |                           |                                |
| NHL                            |                                                                                                                                                    |                                                                                                |                           |                                |
| Chlorambucil                   |                                                                                                                                                    |                                                                                                |                           |                                |
| 13                             | Y                                                                                                                                                  |                                                                                                |                           |                                |
| (PO)                           | Hodgkin's  Lymphoma                                                                                                                                | 0.2mg/kg/day x 3-6 weeks                                                                       |                           |                                |  
Version Date: March 21, 2019  
| Version Date: March 21, 2019                       | Formulary  Status                                                            |                                                       |                                 |                                                         |
|----------------------------------------------------|------------------------------------------------------------------------------|-------------------------------------------------------|---------------------------------|---------------------------------------------------------|
| Drug Name and                                      |                                                                              |                                                       |                                 |                                                         |
| #                                                  | route of                                                                     |                                                       |                                 |                                                         |
| administration                                     | FDA-Approved                                                                 | FDA-Approved Dose &                                   |                                 |                                                         |
| Indication                                         | Schedule                                                                     |                                                       |                                 |                                                         |
| (Y, yes; N,  no)                                   | Bladder, advanced                                                            | 50-70mg/m2  Q3-4weeks  Single Agent: 100mg/m2 Q4weeks |                                 |                                                         |
| Ovarian,                                           |                                                                              |                                                       |                                 |                                                         |
| 14                                                 | Cisplatin                                                                    | Y                                                     |                                 |                                                         |
| (IV)                                               | Combination Therapy: 75-100 mg/m2 Q4weeks                                    |                                                       |                                 |                                                         |
| metastatic Testicular, metastatic                  | 20mg/m2 /day x 5 days Q3weeks                                                |                                                       |                                 |                                                         |
| Cladribine                                         | Y                                                                            | Hairy Cell Leukemia                                   | 0.09mg/kg/day CIVI x 7 days x 1 |                                                         |
| 15                                                 | (IV)                                                                         | cycle                                                 |                                 |                                                         |
| Clofarabine                                        | ALL,                                                                         |                                                       |                                 |                                                         |
| 16                                                 | N                                                                            | adults ≤ 21 years                                     | 52mg/m2 /day days 1-5 Q2-6weeks |                                                         |
| (IV) Crizotinib                                    | NSCLC, metastatic,                                                           |                                                       |                                 |                                                         |
| 17                                                 | N                                                                            | ALK-positive                                          | 250mg BID                       |                                                         |
| (PO) Cytarabine                                                    | Combination Therapy:  100mg/m2 /day CIVI x 7 days OR                         |                                                       |                                 |                                                         |
| Y                                                  | AML, remission  induction                                                    |                                                       |                                 |                                                         |
| 18                                                 | Conventional                                                                 | 100mg/m2  Q12hours x 7 days                           |                                 |                                                         |
| (IV)                                               | Combination Therapy:                                                         |                                                       |                                 |                                                         |
| Hodgkin's Disease                                  | 375mg/m2 /dose days 1 & 15  Q4weeks                                          |                                                       |                                 |                                                         |
| Dacarbazine                                        |                                                                              |                                                       |                                 |                                                         |
| 19                                                 | Y                                                                            |                                                       |                                 |                                                         |
| (IV)                                               | Melanoma,  metastatic                                                        | 250mg/m2 /dose days 1-5 Q3weeks                       |                                 |                                                         |
| Testicular, metastatic                             | Combination Therapy: 1000mcg/m2 on day 1 Single Agent: 12mcg/kg/day x 5 days |                                                       |                                 |                                                         |
| Gestational  Trophoblastic  Neoplasm               |                                                                              |                                                       |                                 |                                                         |
| 20                                                 | Dactinomycin                                                                 | N                                                     |                                 |                                                         |
| (IV)                                               | Combination Therapy: 500mcg/dose  days 1 and 2                               |                                                       |                                 |                                                         |
| Wilms' Tumor,  Ewing's Sarcoma,  Rhabdomyo-sarcoma | Combination Therapy: 15mcg/kg/day  x 5 days                                  |                                                       |                                 |                                                         |
| 21                                                 | Dasatinib                                                                    | Y                                                     | CML, Ph+                        | Chronic Phase: 100mg Qday (may  increase to 140mg Qday) |  
| Version Date: March 21, 2019   | Formulary  Status                                                                         |                                                     |                                 |                                                                     |
|--------------------------------|-------------------------------------------------------------------------------------------|-----------------------------------------------------|---------------------------------|---------------------------------------------------------------------|
| Drug Name and                  |                                                                                           |                                                     |                                 |                                                                     |
| #                              | route of                                                                                  |                                                     |                                 |                                                                     |
| administration                 | FDA-Approved                                                                              | FDA-Approved Dose &                                 |                                 |                                                                     |
| Indication                     | Schedule                                                                                  |                                                     |                                 |                                                                     |
| (Y, yes; N,  no)               |                                                                                           |                                                     |                                 |                                                                     |
| (PO)                           | Accelerated or Blast Phase: 140mg  Qday (may increase to 180mg Qday)  Initial: 140mg Qday |                                                     |                                 |                                                                     |
| ALL, Ph+                       | Dose Increases: may increase to  180mg Qday                                               |                                                     |                                 |                                                                     |
| ALL                            | Combination Therapy: 45mg/m2 /day  x 3 days Q3-4weeks  Combination Therapy                |                                                     |                                 |                                                                     |
| AML, induction,                | Cycle 1: 45mg/m2 /day x 3 days                                                            |                                                     |                                 |                                                                     |
| Daunorubicin                                | adults <60 years                                                                          | Subsequent Cycles: 45mg/m2 /day x 2  days Q3-4weeks |                                 |                                                                     |
| 22                             | Conventional                                                                              | Y                                                   |                                 |                                                                     |
| (IV)                           | Combination Therapy                                                                       |                                                     |                                 |                                                                     |
| AML, induction,                | Cycle 1: 30mg/m2 /day x 3 days                                                            |                                                     |                                 |                                                                     |
| elderly ≥ 60 years             | Subsequent Cycles: 30mg/m2 /day x 2  days Q3-4weeks                                       |                                                     |                                 |                                                                     |
| Decitabine                     | N                                                                                         | MDS                                                 | 15mg/m2 Q8H x 3 days Q6weeks OR |                                                                     |
| 23                             | (IV)                                                                                      | 20mg/m2 Qday x 5 days Q4weeks                       |                                 |                                                                     |
| Breast                         | 60-100mg/m2  Q3weeks                                                                      |                                                     |                                 |                                                                     |
| NSCLC                          | 75mg/m2  Q3weeks                                                                          |                                                     |                                 |                                                                     |
| Prostate                       | 75mg/m2 Q3weeks w/prednisone                                                              |                                                     |                                 |                                                                     |
| Gastric Adenocarcinoma                                | 75mg/m2 Q3weeks w/cisplatin and  fluorouracil                                             |                                                     |                                 |                                                                     |
| Docetaxel                      |                                                                                           |                                                     |                                 |                                                                     |
| 24                             | Y                                                                                         |                                                     |                                 |                                                                     |
| (IV)                           | 75mg/m2 Q3weeks w/cisplatin and                                                           |                                                     |                                 |                                                                     |
| Head and Neck                  | fluorouracil x 3-4 weeks, followed  by RT Single Agent: 100mg/m2 Q3weeks                  |                                                     |                                 |                                                                     |
| Bladder                        | Combination Therapy: 35mg/m2 day  1 and 8 Q21 days w/ gemcitabine and  cisplatin          |                                                     |                                 |                                                                     |
| (unlabeled use)                |                                                                                           |                                                     |                                 |                                                                     |
| 25                             | Doxorubicin-                                                                              | Y                                                   | Breast                          | 60mg/m2  on day 1 of a 21-day cycle  x 4 cycles w/ cyclophosphamide |  
| Version Date: March 21, 2019   | Formulary  Status                            |                                                                                                                                                                                                       |                             |
|--------------------------------|----------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------|
| Drug Name and                  |                                              |                                                                                                                                                                                                       |                             |
| #                              | route of                                     |                                                                                                                                                                                                       |                             |
| administration                 | FDA-Approved                                 | FDA-Approved Dose &                                                                                                                                                                                   |                             |
| Indication                     | Schedule                                     |                                                                                                                                                                                                       |                             |
| (Y, yes; N,  no)               |                                              |                                                                                                                                                                                                       |                             |
| Conventional                   | Single Agent: 60-75mg/m2 Q21days             |                                                                                                                                                                                                       |                             |
| Metastatic Solid               |                                              |                                                                                                                                                                                                       |                             |
| (IV)                           | Tumors, Leukemia,  or Lymphoma               | Combination Therapy: 40-75mg/m2 Q21-28days  60mg/m2 day 1 and 8 Q28days x 6  cycles w/ cyclophosphamide and  fluorouracil OR 100mg/m2 day 1 Q21days x 6 cycles  w/ cyclophosphamide and  fluorouracil |                             |
| 26                             | Epirubicin                                   | N                                                                                                                                                                                                     | Breast, adjuvant            |
| (IV) Eribulin                  | N                                            | Breast, metastatic                                                                                                                                                                                    | 1.4mg/m2 /dose days 1 and 8 |
| 27                             | Q21days                                      |                                                                                                                                                                                                       |                             |
| (IV)                           | NSCLC,  first-line EGFR  mutations           | 150mg Qday                                                                                                                                                                                            |                             |
| Erlotinib                      |                                              |                                                                                                                                                                                                       |                             |
| 28                             | Y                                            |                                                                                                                                                                                                       |                             |
| (PO)                           | NSCLC, refractory or  maintenance Pancreatic | 100mg Qday                                                                                                                                                                                            |                             |
| Estramustine                   | Y                                            | Prostate, progressive                                                                                                                                                                                 |                             |
| 29                             | or metastatic                                | 14mg/kg/day (3 to 4 divided doses)                                                                                                                                                                    |                             |
| (PO)                           | SCLC                                         | 35mg/m2 /day x 4 days, up to  50mg/m2 /day x 5 days Q3-4weeks                                                                                                                                         |                             |
| 30                             | Etoposide                                    | N                                                                                                                                                                                                     |                             |
| (IV)                           | 50-100mg/m2 /day x 5 days OR                 |                                                                                                                                                                                                       |                             |
| Testicular                     | 100mg/m2 /day days 1, 3, and 5 Q3- 4weeks    |                                                                                                                                                                                                       |                             |
| Etoposide                      | Y                                            | SCLC                                                                                                                                                                                                  | PO twice IV dose            |
| (PO) Exemestane                |                                              |                                                                                                                                                                                                       |                             |
| 31                             | N                                            | Breast                                                                                                                                                                                                | 25mg Qday                   |
| (PO) Floxuridine               | CRC,                                         | 0.1-0.6mg/kg/day continuous                                                                                                                                                                           |                             |
| 32                             | N                                            |                                                                                                                                                                                                       |                             |
| (intra-arterial)               | hepatic mets                                 | infusion                                                                                                                                                                                              |                             |  
Version Date: March 21, 2019  
| Version Date: March 21, 2019                          | Formulary  Status                                                                                                                                                                             |                                                                                                                                                                                                          |                                  |
|-------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------|
| Drug Name and                                         |                                                                                                                                                                                               |                                                                                                                                                                                                          |                                  |
| #                                                     | route of                                                                                                                                                                                      |                                                                                                                                                                                                          |                                  |
| administration                                        | FDA-Approved                                                                                                                                                                                  | FDA-Approved Dose &                                                                                                                                                                                      |                                  |
| Indication                                            | Schedule                                                                                                                                                                                      |                                                                                                                                                                                                          |                                  |
| (Y, yes; N,  no)                                      |                                                                                                                                                                                               |                                                                                                                                                                                                          |                                  |
| Fludarabine                                           |                                                                                                                                                                                               |                                                                                                                                                                                                          |                                  |
| 33                                                    | Y                                                                                                                                                                                             | CLL                                                                                                                                                                                                      | 25mg/m2 /day x 5 days Q28days    |
| (IV)                                                  | Breast                                                                                                                                                                                        | Initial Course: 12mg/kg Qday x 4  days then 6mg/kg days 6, 8, 10 and  12 Maintenance Therapy: repeat dosage  of initial course every 30 days after  the last day of previous course OR  10-15mg/kg Qweek |                                  |
| CRC                                                   |                                                                                                                                                                                               |                                                                                                                                                                                                          |                                  |
| Fluorouracil                                          |                                                                                                                                                                                               |                                                                                                                                                                                                          |                                  |
| 34                                                    | Y                                                                                                                                                                                             |                                                                                                                                                                                                          |                                  |
| (IV)                                                  | Pancreatic Gastric NSCLC,                                                                                                                                                                     |                                                                                                                                                                                                          |                                  |
| Gefitinib                                             |                                                                                                                                                                                               |                                                                                                                                                                                                          |                                  |
| 35                                                    | N                                                                                                                                                                                             | 250mg Qday                                                                                                                                                                                               |                                  |
| first-line EGFR                                       |                                                                                                                                                                                               |                                                                                                                                                                                                          |                                  |
| (PO)                                                  | mutations Breast,                                                                                                                                                                             | 1250mg/m2 days 1 and 8 Q21days w/                                                                                                                                                                        |                                  |
| metastatic                                            | paclitaxel  1000mg/m2  days 1, 8, and 15  Q28days w/ cisplatin OR 1250mg/m2 days 1 and 8 Q21days  w/cisplatin                                                                                 |                                                                                                                                                                                                          |                                  |
| NSCLC, locally  advanced or  metastatic Ovarian,      |                                                                                                                                                                                               |                                                                                                                                                                                                          |                                  |
| Gemcitabine                                           |                                                                                                                                                                                               |                                                                                                                                                                                                          |                                  |
| 36                                                    | Y                                                                                                                                                                                             |                                                                                                                                                                                                          |                                  |
| (IV)                                                  | 1000mg/m2 days 1 and 8 Q21days w/  carboplatin                                                                                                                                                |                                                                                                                                                                                                          |                                  |
| advanced Pancreatic, locally  advanced or  metastatic | 1000mg/m2  Qweek x 7 weeks  followed by 1 week rest THEN  Qweek x 3 weeks every 4 weeks 1000mg/m2 days 1, 8, and 15 Q28  days w/ cisplatin OR 1000mg/m2 days 1 and 8 Q21 days  w/ carboplatin |                                                                                                                                                                                                          |                                  |
| Bladder (unlabeled use) CML, resistant                | 20-30mg/kg Qday                                                                                                                                                                               |                                                                                                                                                                                                          |                                  |
| 37                                                    | Hydroxyurea                                                                                                                                                                                   | Y                                                                                                                                                                                                        |                                  |
| (PO)                                                  | Solid Tumors (Head  and Neck,  Melanoma, Ovarian)                                                                                                                                             | Intermittent: 80mg/kg Q3days  Continuous: 20-30mg/kg Qday                                                                                                                                                |                                  |
| Idarubicin                                            |                                                                                                                                                                                               |                                                                                                                                                                                                          |                                  |
| 38                                                    | Y                                                                                                                                                                                             | AML                                                                                                                                                                                                      | Induction: 12mg/m2 /day x 3 days |
| (IV)                                                  |                                                                                                                                                                                               |                                                                                                                                                                                                          |                                  |  
Version Date: March 21, 2019  
| Version Date: March 21, 2019   | Formulary  Status                                                                                                                 |                                                               |                                         |                                         |
|--------------------------------|-----------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------|-----------------------------------------|-----------------------------------------|
| Drug Name and                  |                                                                                                                                   |                                                               |                                         |                                         |
| #                              | route of                                                                                                                          |                                                               |                                         |                                         |
| administration                 | FDA-Approved                                                                                                                      | FDA-Approved Dose &                                           |                                         |                                         |
| Indication                     | Schedule                                                                                                                          |                                                               |                                         |                                         |
| (Y, yes; N,  no)               | Consolidation: 10-12mg/m2 /day x 2  days                                                                                          |                                                               |                                         |                                         |
| Ifosfamide                     | Y                                                                                                                                 | Testicular                                                    | 1200mg/m2 /day x 5 days Q3weeks,        |                                         |
| 39                             | combo therapy & w/mesna                                                                                                           |                                                               |                                         |                                         |
| (IV)                           | Chronic Phase: 400mg Qday, may  increase to 600mg Qday Accelerated Phase or Blast Crisis:  600mg Qday, may increase to 400mg  BID |                                                               |                                         |                                         |
| CML, Ph+                       |                                                                                                                                   |                                                               |                                         |                                         |
| Imatinib                       |                                                                                                                                   |                                                               |                                         |                                         |
| 40                             | Y                                                                                                                                 |                                                               |                                         |                                         |
| (PO)                           | GIST                                                                                                                              | 400mg Qday, may increase to 400mg  BID                        |                                         |                                         |
| ALL, Ph+                       | 600mg Qday  125mg/m2 days 1, 8, 15, and 22 of a                                                                                   |                                                               |                                         |                                         |
| Irinotecan                     |                                                                                                                                   |                                                               |                                         |                                         |
| 41                             | Y                                                                                                                                 | CRC, metastatic                                               | 6 week cycle OR                         |                                         |
| (IV)                           | 350mg/m2  Q3weeks                                                                                                                 |                                                               |                                         |                                         |
| 42                             | Ixabepilone                                                                                                                       | N                                                             | Breast, metastatic or  locally advanced | 40mg/m2 /dose Q3 weeks, max 88mg        |
| (IV)                           |                                                                                                                                   |                                                               |                                         |                                         |
| 43                             | Lapatinib                                                                                                                         | N                                                             | Breast, HER2+                           | 1250mg Qday w/ capecitabine OR          |
| (PO)                           | 1500mg Qday w/ letrozole                                                                                                          |                                                               |                                         |                                         |
| Brain Tumors                   |                                                                                                                                   |                                                               |                                         |                                         |
| Lomustine                      |                                                                                                                                   |                                                               |                                         |                                         |
| 44                             | N                                                                                                                                 |                                                               |                                         |                                         |
| (PO)                           | 130mg/m2  Q6weeks                                                                                                                 |                                                               |                                         |                                         |
| Hodgkin's  Lymphoma            |                                                                                                                                   |                                                               |                                         |                                         |
| Mechlor                                | Hodgkin's                                                                                                                         |                                                               |                                         |                                         |
| Y                              | 0.4mg/kg                                                                                                                          |                                                               |                                         |                                         |
| Lymphoma,  palliative          |                                                                                                                                   |                                                               |                                         |                                         |
| 45                             | Ethamine (IV)                                                                                                                     |                                                               |                                         |                                         |
| 46                             | Melphalan                                                                                                                         | Y                                                             | MM, palliative                          | 16mg/m2 Q2weeks x 4 doses then  Q4weeks |
| (IV)                           | MM, palliative                                                                                                                    | 6mg Qday x 2-3 weeks, followed by  4 weeks rest then 2mg Qday |                                         |                                         |
| Y                              |                                                                                                                                   |                                                               |                                         |                                         |
| (PO) Melphalan                 | Ovarian                                                                                                                           | 0.2mg/kg/day x 5 days Q4-5weeks                               |                                         |                                         |  
Version Date: March 21, 2019  
| Version Date: March 21, 2019   | Formulary  Status                                                                                                                                         |                                                                                                                                   |                                      |                    |
|--------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------|--------------------------------------|--------------------|
| Drug Name and                  |                                                                                                                                                           |                                                                                                                                   |                                      |                    |
| #                              | route of                                                                                                                                                  |                                                                                                                                   |                                      |                    |
| administration                 | FDA-Approved                                                                                                                                              | FDA-Approved Dose &                                                                                                               |                                      |                    |
| Indication                     | Schedule                                                                                                                                                  |                                                                                                                                   |                                      |                    |
| (Y, yes; N,  no)               |                                                                                                                                                           |                                                                                                                                   |                                      |                    |
| Mercapto                                |                                                                                                                                                           |                                                                                                                                   |                                      |                    |
| 47                             | Purine                                                                                                                                                    | Y                                                                                                                                 | ALL                                  | 1.5-2.5mg/kg Qday  |
| (PO)                           | Intrathecal: 15mg day 1, 8, 15, 22,  and 29; 12mg Q2-7days  IV (large range of approved doses):  40mg/m2  Qweek; 12gm/m2 (max  20gm) weeks 3, 4, 8, and 9 |                                                                                                                                   |                                      |                    |
| Methotrexate                   | Y                                                                                                                                                         | Numerous OncologyRelated Indications                                                                                                                                   |                                      |                    |
| 48                             | (intrathecal, IV, IM,  SubQ) Methotrexate                                                                                                                 | Y                                                                                                                                 | Numerous OncologyRelated Indications                                      | 20mg/m2  Qweek     |
| (PO)                           |                                                                                                                                                           |                                                                                                                                   |                                      |                    |
| 49                             | Mitomycin                                                                                                                                                 | Y                                                                                                                                 | Stomach or Pancreas  Adeno-carcinoma | 20mg/m2  Q6-8weeks |
| (IV) Mitotane                  | 2-6gm Qday (divided) then increase                                                                                                                        |                                                                                                                                   |                                      |                    |
| 50                             | Y                                                                                                                                                         | ACC                                                                                                                               | incrementally to 9-10gm Qday         |                    |
| (PO)                           | (divided)  Induction: 12mg/m2 Qday x 3 days  w/ cytarabine Consolidation (6 weeks after  induction): 12mg/m2 Qday x 2 days,  repeat in 4 weeks            |                                                                                                                                   |                                      |                    |
| ANLL                           |                                                                                                                                                           |                                                                                                                                   |                                      |                    |
| Mitoxantrone                   |                                                                                                                                                           |                                                                                                                                   |                                      |                    |
| 51                             | N                                                                                                                                                         |                                                                                                                                   |                                      |                    |
| (IV)                           | Prostate, advanced,  hormone-refractory                                                                                                                   | 12-14mg/m2  Q3weeks w/ steroids Newly-Diagnosed in Chronic Phase:  300mg BID  Resistant, Chronic or Accelerated  Phase: 400mg BID |                                      |                    |
| Nilotinib                      |                                                                                                                                                           |                                                                                                                                   |                                      |                    |
| 52                             | Y                                                                                                                                                         | CML, Ph+                                                                                                                          |                                      |                    |
| (PO)                           |                                                                                                                                                           |                                                                                                                                   |                                      |                    |
| 53                             | Oxaliplatin                                                                                                                                               | Y                                                                                                                                 | CRC                                  | 85mg/m2  Q2weeks   |
| (IV) Paclitaxel                | 135-175mg/m2  Q3weeks OR                                                                                                                                  |                                                                                                                                   |                                      |                    |
| 54                             | Y                                                                                                                                                         | Ovarian                                                                                                                           |                                      |                    |
| (IV)                           | 50-80mg/m2  Qweek OR                                                                                                                                      |                                                                                                                                   |                                      |                    |  
| Version Date: March 21, 2019              | Formulary  Status                                                                                                      |                                              |                 |
|-------------------------------------------|------------------------------------------------------------------------------------------------------------------------|----------------------------------------------|-----------------|
| Drug Name and                             |                                                                                                                        |                                              |                 |
| #                                         | route of                                                                                                               |                                              |                 |
| administration                            | FDA-Approved                                                                                                           | FDA-Approved Dose &                          |                 |
| Indication                                | Schedule                                                                                                               |                                              |                 |
| (Y, yes; N,  no)                          | 1.4-4mg/m2 /day CIVI x 14 days  Q4weeks 175-250mg/m2  Q3weeks OR  50-80mg/m2  Qweek OR                                 |                                              |                 |
| Breast, metastatic                        | 1.4-4mg/m2 /day CIVI x 14 days  Q4weeks                                                                                |                                              |                 |
| NSCLC                                     | 135mg/m2  Q3weeks  135mg/m2  Q3weeks OR                                                                                |                                              |                 |
| AIDS-Related  Kaposi's Sarcoma            | 100mg/m2  Q2weeks                                                                                                      |                                              |                 |
| RCC                                       |                                                                                                                        |                                              |                 |
| 55                                        | Pazopanib                                                                                                              | N                                            |                 |
| (PO)                                      | 800mg Qday                                                                                                             |                                              |                 |
| Soft Tissue Sarcoma,  advanced refractory |                                                                                                                        |                                              |                 |
| Pentostatin                               |                                                                                                                        |                                              |                 |
| 56                                        | Y                                                                                                                      | Hairy Cell Leukemia                          | 4mg/m2  Q2weeks |
| (IV)                                      | Cutaneous T-cell  Lymphoma                                                                                             | 14mg/m2  days 1, 8 and 15 of a 28- day cycle |                 |
| Peripheral T-cell  Lymphoma               |                                                                                                                        |                                              |                 |
| Romidepsin                                |                                                                                                                        |                                              |                 |
| 57                                        | N                                                                                                                      |                                              |                 |
| (IV)                                      | Platelets >200,000/mm3 : 20mg BID  Platelets 100,000-200,000/mm3 :  15mg BID  Platelets 50,000-<100,000/mm3 : 5mg  BID |                                              |                 |
| Ruxolitinib                               |                                                                                                                        |                                              |                 |
| 58                                        | N                                                                                                                      | Myelofibrosis                                |                 |
| (PO)                                      | HCC                                                                                                                    |                                              |                 |
| Sorafenib                                 |                                                                                                                        |                                              |                 |
| 59                                        | Y                                                                                                                      |                                              |                 |
| (PO)                                      | 400mg BID                                                                                                              |                                              |                 |
| RCC, advanced Thyroid,  differentiated    | 500mg/m2 /day x 5 days Q6 weeks                                                                                        |                                              |                 |
| 60                                        | Streptozocin                                                                                                           | OR                                           |                 |
| Y                                         | Pancreatic Islet Cell                                                                                                  |                                              |                 |
| (IV)                                      | 1000mg/m2  Qweek                                                                                                       |                                              |                 |  
Version Date: March 21, 2019  
| Version Date: March 21, 2019   | Formulary  Status                             |                                      |                                |                                                    |
|--------------------------------|-----------------------------------------------|--------------------------------------|--------------------------------|----------------------------------------------------|
| Drug Name and                  |                                               |                                      |                                |                                                    |
| #                              | route of                                      |                                      |                                |                                                    |
| administration                 | FDA-Approved                                  | FDA-Approved Dose &                  |                                |                                                    |
| Indication                     | Schedule                                      |                                      |                                |                                                    |
| (Y, yes; N,  no)               | GIST                                          | 50mg Qday x 4 weeks Q6weeks          |                                |                                                    |
| RCC, advanced                  |                                               |                                      |                                |                                                    |
| Sunitinib                      |                                               |                                      |                                |                                                    |
| 61                             | Y                                             |                                      |                                |                                                    |
| (PO)                           | PNET, advanced                                | 37.5mg Qday                          |                                |                                                    |
| Tamoxifen                      |                                               |                                      |                                |                                                    |
| 62                             | Y                                             | Breast                               | 20mg Qday                      |                                                    |
| (PO) Temsirolimus              |                                               |                                      |                                |                                                    |
| 63                             | N                                             | RCC                                  | 25mg Qweek                     |                                                    |
| (IV)                           |                                               |                                      |                                |                                                    |
| 64                             | Teniposide                                    | N                                    | ALL, pediatric                 | 165-250 mg/m2 twice weekly or  weekly x 8-9 doses. |
| (IV)                           |                                               |                                      |                                |                                                    |
| 65                             | Thioguanine                                   | Y                                    | AML                            | 2mg/kg Qday                                        |
| (PO)                           | Bladder                                       | 60mg Qweek x 4 weeks  (intravesical) |                                |                                                    |
| 66                             | Thiotepa                                      | N                                    |                                |                                                    |
| (intravesical, IV)             | Ovarian                                       | 0.3-0.4mg/kg Q1-4weeks (IV)          |                                |                                                    |
| Breast Cervical                | 0.75mg/m2 /day x 3 days Q21days w/  cisplatin |                                      |                                |                                                    |
| 67                             | Topotecan                                     | Y                                    |                                |                                                    |
| (IV)                           | Ovarian                                       | 1.5mg/m2 /day x 5 days Q21days       |                                |                                                    |
| SCLC                           |                                               |                                      |                                |                                                    |
| Topotecan                      | N                                             | SCLC                                 | 2.3mg/m2 /day x 5 days Q21days |                                                    |
| (PO) Toremifene                |                                               |                                      |                                |                                                    |
| 68                             | N                                             | Breast, metastatic                   | 60mg Qday                      |                                                    |
| (PO) Tretinoin                 | Y                                             | APL                                  | 45mg/m2 /day (divided)         |                                                    |
| 69                             | (PO)                                          |                                      |                                |                                                    |  
Version Date: March 21, 2019  
| Formulary  Status   |                                                                                                                                                                                                                    |                     |                                             |            |
|---------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------|---------------------------------------------|------------|
| Drug Name and       |                                                                                                                                                                                                                    |                     |                                             |            |
| #                   | route of                                                                                                                                                                                                           |                     |                                             |            |
| administration      | FDA-Approved                                                                                                                                                                                                       | FDA-Approved Dose & |                                             |            |
| Indication          | Schedule                                                                                                                                                                                                           |                     |                                             |            |
| (Y, yes; N,  no)    | MTC, locally                                                                                                                                                                                                       |                     |                                             |            |
| Vandetanib          |                                                                                                                                                                                                                    |                     |                                             |            |
| 70                  | N                                                                                                                                                                                                                  | advanced or         | 300mg Qday                                  |            |
| (PO)                | metastatic Melanoma,  metastatic or  unresectable,  BRAFV600E  mutation                                                                                                                                            |                     |                                             |            |
| Vemurafenib         |                                                                                                                                                                                                                    |                     |                                             |            |
| 71                  | N                                                                                                                                                                                                                  |                     |                                             |            |
| (PO)                | 960mg BID  Typical dosages: 3.7mg/m2 (initial),  up to 5.5mg/m2  (dose 2), up to  7.4mg/m2 (dose 3), up to 9.25mg/m2 (dose 4), and up to 11.1mg/m2 (dose  5); administered Q7days Usual Range: 5.5-7.4mg/m2 Q7days |                     |                                             |            |
| Vinblastine         | Hodgkin's, NHL,                                                                                                                                                                                                    |                     |                                             |            |
| 72                  | Y                                                                                                                                                                                                                  | Testicular, Breast, |                                             |            |
| (IV)                | Kaposi's Sarcoma                                                                                                                                                                                                   |                     |                                             |            |
| Vincristine         | Y                                                                                                                                                                                                                  | Numerous OncologyRelated Indications                     | 1.4mg/m2 /dose, max 2mg/dose,               |            |
| 73                  | various frequencies                                                                                                                                                                                                |                     |                                             |            |
| (IV)                |                                                                                                                                                                                                                    |                     |                                             |            |
| 74                  | Vismodegib                                                                                                                                                                                                         | N                   | Basal Cell, metastatic  or locally advanced | 150mg Qday |
| (PO) Vorinostat     | Cutaneous                                                                                                                                                                                                          |                     |                                             |            |
| 75                  | N                                                                                                                                                                                                                  | T-cell Lymphoma     | 400mg Qday                                  |            |
| (PO)                |                                                                                                                                                                                                                    |                     |                                             |            |  
| Tumor blocks will be submitted to Maria Merino  for cutting into slides.   | Unstained slides will be distributed by research  nurse to:   | Laboratory of pathology, Dr. Merino:5 unstained  slides and 1 H&E           | Meltzer's lab for NGS: 10 unstained slides and 1  H&E   | Trepel's lab for Immune gene signature: 10  unstained slides and 1 H&E   | Fresh tumor will be fixed and submitted to Maria  Merino for processing.   | Unstained Slides will be distributed by research  nurse to:   | Meltzer's lab for NGS: 10 unstained slides and 1  H&E   | Trepel's lab for Immune gene signature: 10  unstained slides and 1 H&E   |
|----------------------------------------------------------------------------|---------------------------------------------------------------|-----------------------------------------------------------------------------|---------------------------------------------------------|--------------------------------------------------------------------------|----------------------------------------------------------------------------|---------------------------------------------------------------|---------------------------------------------------------|--------------------------------------------------------------------------|
| Special Instructions                                                       |                                                               |                                                                             |                                                         |                                                                          |                                                                            |                                                               |                                                         |                                                                          |
| Abbreviated Title: COXEN study  Version Date: March 21, 2019               | 12.3 APPENDIX C: SAMPLE COLLECTION FOR CORRELATIVE STUDIES    | The date and exact time of each blood draw should be recorded on each tube. | Test description                                        |                                                                          |                                                                            |                                                               |                                                         |                                                                          |
| Amount/Type/ Tube/Handling Collection Timing                               | Marissa Mallek,  marissa.mallek@nih.gov, 240-760-7498         | Marissa Mallek,  marissa.mallek@nih.gov, Ph: 240-760-7498                   | Dr. Bottaro,  don.bottaro@nih.gov,  Ph: 301-402-6499    | Rene Costello,  rene.costello@nih.gov, Ph: 301-443-6915 to               | arrange for pick-up                                                        |                                                               |                                                         |                                                                          |
| Contact                                                                    | Baseline (mandatory)  and at progression  (optional)          |                                                                             |                                                         |                                                                          |                                                                            |                                                               |                                                         |                                                                          |
| (Pre treatment)                                                            |                                                               |                                                                             |                                                         |                                                                          |                                                                            |                                                               |                                                         |                                                                          |
| Baseline  unstained slides                                                 | and 2 H&E                                                     | slides  (Sample 1)                                                          |                                                         |                                                                          |                                                                            |                                                               |                                                         |                                                                          |
| blocks or 25                                                               |                                                               |                                                                             |                                                         |                                                                          |                                                                            |                                                               |                                                         |                                                                          |
| 1-2 Tumor                                                                  | Archival Tissue                                               | (Sample 2 and  Sample 5)                                                    |                                                         |                                                                          |                                                                            |                                                               |                                                         |                                                                          |
| 2-3 cores  Fresh Tumor  Biopsy                                             |                                                               |                                                                             |                                                         |                                                                          |                                                                            |                                                               |                                                         |                                                                          |  
| Patient should not eat or drink anything 30  minutes prior to collection.   | After the sample collection, when the top of the  device is closed a preservative is released.  Remove the top and close the tube with a cap.   | Store at room temperature.                          | Invert Streck tube 2-4 times, keep at room  temperature (15- 30 degrees C) and transferr to  the lab for processing .   | Invert several times and keep at room temp   |                               |                                                      |
|-----------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------|----------------------------------------------|-------------------------------|------------------------------------------------------|
| Special Instructions                                                        | Developmental  Therapeutics Branch:                                                                                                             | Jane Trepel,  trepelj@mail.nih.gov                  | Yusuke Tomita,  yusuke.tomita@nih.gov                                                                                   | Sunmin Lee,  lees@pop.nci.gov                | Mi-Jung  leemin@,mail.nih.gov | Call 240-760-6330  immediately after blood is  drawn |
| Baseline (just prior to  beginning therapy),  C2D1 and C3D1                 |                                                                                                                                                 |                                                     |                                                                                                                         |                                              |                               |                                                      |
| Marissa Mallek,                                                             | marissa.mallek@nih.gov,  24 hours prior to  anticipated collection.                                                                             | Call 240-760-7498 for  immediate pick-up of  sample |                                                                                                                         |                                              |                               |                                                      |
| consent is signed, but  preferably at baseline)                             |                                                                                                                                                 |                                                     |                                                                                                                         |                                              |                               |                                                      |
| (at any time after                                                          | Meltzer lab,  pmeltzer@mail.nih.gov.  Email 24 hr prior to  collection. Baseline and C3D1                                                       |                                                     |                                                                                                                         |                                              |                               |                                                      |
| Contact                                                                     |                                                                                                                                                 |                                                     |                                                                                                                         |                                              |                               |                                                      |
| Abbreviated Title: COXEN study  Version Date: March 21, 2019                | Test description                                                                                                                                |                                                     |                                                                                                                         |                                              |                               |                                                      |
| Amount/Type/ Tube/Handling Collection Timing                                | Baseline                                                                                                                                        | saliva collection  kit (DNA  Genotek)               |                                                                                                                         |                                              |                               |                                                      |
| 3 mL; Oragene                                                               | 10 mL of blood;  Streck tube  (Streck, Omaha,  NE)                                                                                              | (Sample 3 and  Sample 4)                            |                                                                                                                         |                                              |                               |                                                      |
| ctDNA isolation                                                             | 8 mL of blood;  two BD  Vacutainer Cell  Preparation  Tubes (CPT)  citrate  Immune Subset  analysis                                             |                                                     |                                                                                                                         |                                              |                               |                                                      |
| Saliva                                                                      |                                                                                                                                                 |                                                     |                                                                                                                         |                                              |                               |                                                      |  
| Invert EDTA tube 2-4 times, place on wet ice and  store at 4°C until processing for a maximum of  30-60 min.   | Upon arrival in the BPC, blood samples will be  centrifuged for 5 minutes at 1200 x g at 4qC.  Plasma will be aliquoted into 2 cryovials and  stored at -80qC until the time of analysis.   |                                     |                                                                                                                                          |                               |                               |
|----------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------|-------------------------------|
| Invert several times and keep at room temp                                                                     |                                                                                                                                                                                             |                                     |                                                                                                                                          |                               |                               |
| Special Instructions                                                                                           | Figg lab.  NCIBloodcore@mail.nih. gov.  Contact 24 hr prior or for  questions regarding  sample processing.                                                                                 | Page 102-11964 for  sample pick-up. | For immediate help, call  240-760-6180 (main blood  processing core number)  or, 240-760-6190 (main  clinical pharmacology lab  number). |                               |                               |
| Developmental  Therapeutics Branch :                                                                           | Phone: 240-760-6330                                                                                                                                                                         | Jane Trepel,  trepelj@mail.nih.gov  | Yusuke Tomita,  yusuke.tomita@nih.gov                                                                                                    | Sunmin Lee,  lees@pop.nci.gov | Mi-Jung,  leemin@mail.nih.gov |
| Contact                                                                                                        | Baseline (just prior to  beginning therapy)  and C2D1  2.5 ml of blood;  one PAXgene  RNA tube  (PreAnalytix)  Blood Immune  Gene  Expression  Peripheral                                   |                                     |                                                                                                                                          |                               |                               |
| Abbreviated Title: COXEN study  Version Date: March 21, 2019                                                   | Test description                                                                                                                                                                            |                                     |                                                                                                                                          |                               |                               |
| Amount/Type/ Tube/Handling Collection Timing                                                                   | Baseline, C2D1,  and C3D1  10 mL of blood;  one EDTA tube  Inflammatory  Cytokines  Pro                                                                                                                                                                                             |                                     |                                                                                                                                          |                               |                               |  
| 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.   | Upon arrival in the BPC, samples will be  centrifuged and the plasma transferred into  cryovials for storage at -80 C until the time of  analysis.  Samples will be barcoded as described   | 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. The date and exact  time of each blood draw should be recorded on  the sample tube and on the PK sheet.   | Upon arrival in the Clinical Pharmacology Lab,  samples will be centrifuged and the plasma  transferred into cryovials for storage at -80°C  until the time of analysis. Samples will be  barcoded as described in Section 5.3   |                                     |                                                                                                                                          |
|------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------|
| Special Instructions                                                                                                               | in Section 5.3.                                                                                                                                                                             |                                                                                                                                                                                                                                            |                                                                                                                                                                                                                                  |                                     |                                                                                                                                          |
| Figg lab.  NCIBloodcore@mail.nih. gov. Contact 24 hr prior or  for questions regarding  sample processing.                         | Page 102-11964 for  sample pick-up.                                                                                                                                                         | For immediate help, call  240-760-6180 (main blood  processing core number)  or, 240-760-6190 (main  clinical pharmacology lab  number).                                                                                                   | Figg lab.  NCIBloodcore@mail.nih. gov. Contact 24 hr prior or  for questions regarding  sample processing.                                                                                                                       | Page 102-11964 for  sample pick-up. | For immediate help, call  240-760-6180 (main blood  processing core number)  or, 240-760-6190 (main  clinical pharmacology lab  number). |
| Contact                                                                                                                            |                                                                                                                                                                                             |                                                                                                                                                                                                                                            |                                                                                                                                                                                                                                  |                                     |                                                                                                                                          |
| Abbreviated Title: COXEN study  Version Date: March 21, 2019                                                                       | Test description                                                                                                                                                                            |                                                                                                                                                                                                                                            |                                                                                                                                                                                                                                  |                                     |                                                                                                                                          |
| Amount/Type/ Tube/Handling Collection Timing                                                                                       | and day 1 of each  treatment cycle                                                                                                                                                          |                                                                                                                                                                                                                                            |                                                                                                                                                                                                                                  |                                     |                                                                                                                                          |
| Baseline                                                                                                                           | Baseline                                                                                                                                                                                    |                                                                                                                                                                                                                                            |                                                                                                                                                                                                                                  |                                     |                                                                                                                                          |
| 4 mL of blood;  one EDTA tube                                                                                                      | 6 mL of blood;  one EDTA tube                                                                                                                                                               |                                                                                                                                                                                                                                            |                                                                                                                                                                                                                                  |                                     |                                                                                                                                          |
| Plasma HGF                                                                                                                         | and MET                                                                                                                                                                                     | DMET                                                                                                                                                                                                                                       |                                                                                                                                                                                                                                  |                                     |                                                                                                                                          |  
| Confirm blood tube is not expired.  Collect minimum of 4 mL blood per sample, but a  full 10 mL tube of blood should be provided when  possible (*see note regarding prevention of  backflow in Section 5.1.9).   | Remove tube from adapter and immediately mix  by gentle inversion 8 to 10 times to prevent  clotting. Inadequate or delayed mixing may result  in inaccurate test results.   | Label the tube with subject's identification and  date and time of blood draw. Unlabeled blood  tubes may not be processed.  Keep sample at room temperature and ship on day  of collection in shipper with ambient gel packs.   |                               |                                          |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------|------------------------------------------|
| detailed in Section 5.1.9.1                                                                                                                                                                                       |                                                                                                                                                                              |                                                                                                                                                                                                                                  |                               |                                          |
| Send to Epic Science as                                                                                                                                                                                           |                                                                                                                                                                              |                                                                                                                                                                                                                                  |                               |                                          |
| Invert several times and place at room temp or  refrigerate                                                                                                                                                       |                                                                                                                                                                              |                                                                                                                                                                                                                                  |                               |                                          |
| Special Instructions                                                                                                                                                                                              | Jane Trepel,  trepelj@mail.nih.gov                                                                                                                                           | Yusuke Tomita,  yusuke.tomita@nih.gov                                                                                                                                                                                            | Sunmin Lee,  lees@pop.nci.gov | Call 240-760-6330 for  immediate pick-up |
| Contact                                                                                                                                                                                                           | Baseline, (just prior to  beginning therapy)and  C2D1  10 ml of blood;  Cell save tube  (Trepel Lab)  Circulating  tumor cells                                               |                                                                                                                                                                                                                                  |                               |                                          |
| Abbreviated Title: COXEN study  Version Date: March 21, 2019                                                                                                                                                      | Test description                                                                                                                                                             |                                                                                                                                                                                                                                  |                               |                                          |
| Amount/Type/ Tube/Handling Collection Timing                                                                                                                                                                      | First Restaging                                                                                                                                                              |                                                                                                                                                                                                                                  |                               |                                          |
| Baseline and  blood; Streck  Cell-Free DNA  BCT                                                                                                                                                                   |                                                                                                                                                                              |                                                                                                                                                                                                                                  |                               |                                          |
| 4-10 mL of                                                                                                                                                                                                        | (Epic Science)                                                                                                                                                               |                                                                                                                                                                                                                                  |                               |                                          |
| Circulating  tumor cells                                                                                                                                                                                          |                                                                                                                                                                              |                                                                                                                                                                                                                                  |                               |                                          |