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14.1.1 participation of children

This study includes patients 18 years of age and older. Because insufficient dosing or adverse event data are currently available on the use of AZD1775 in patients <18 years of age, children are excluded from this study, but may be eligible for future pediatric trials. Studies will be performed in patients <18 years of age when it is appropriate to do so.
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14.2 evaluation of benefits and

There may or may not be any clinical benefit to a patient from participation in this trial. Their participation will benefit future cancer patients. Potential risks include the possible occurrence of any of a range of side effects that are listed in the consent document. The procedure for protecting against or minimizing risks will be to medically evaluate patients as described in Sections 5 and 6. Although no compensation is available, any injury will be fully evaluated and treated in keeping with the benefits or care to which participants are entitled under applicable regulations.  
All patients > 18 years old will be offered the opportunity to assign a substitute decision maker on the "NIH Advance Directive for Health Care and Medical Research Participation" form, so that another person can make decisions about their medical care if they become incapacitated or cognitively impaired. The process for determining whether adults who lose capacity to give consent may continue participation in this trial, with its heavy reliance on non-therapeutic endpoints and collection of research samples, will be on a case-by case basis and will include consultation among the substitute decision maker, protocol PI, and patient's physician regarding the health of the patient and likelihood of benefit from continued treatment.
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14.3 consent and assent process

An associate or principal investigator on the trial will inform patients of the purpose, alternatives, drug administration plan, research objectives, and follow-up of this trial. The patient will be provided an IRB-approved consent for review and signature and his/her questions will be answered. After a decision is made to enroll into the study, a signature will be obtained from the patient. The original signed consent goes to Medical Records; a copy will be placed in the research record. All patients must have a signed informed consent form and an on-study (confirmation of eligibility) form filled out and signed by a participating investigator before entering on study.
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14.4 procedure for protecting against

All care will be taken to minimize side effects, but they can be unpredictable in nature and severity. This study may involve risks to patients, which are currently unforeseeable. All patients will be monitored for side effects from taking study medication. This research represents a greater than minimal risk to participants, but presents the prospect of direct benefit to individual subjects. The research component of this study required to obtain up to 3 CT tumor biopsies confers radiation exposure at an effective dose of 2.4 rem. This dose is below NIH RSC guidelines and represents a slightly greater than minimal risk to patients.
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14.5 patient advocate

The patients' rights representative is available to patients receiving treatment on this protocol at the NIH Clinical Center at (301) 496-2626 in Building 10 of the Clinical Research Center, Room 1-3521, on the Bethesda NIH campus. Patients will be informed that they can contact the study PI or RN at any time with questions about their medical care, and that the patients' rights representative is also available to answer non-medical questions about the study.
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references

1. Jazayeri A et al. ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nature Cell Biology 2006:8:37-45. 2. Dai Y et al. New Insights into Checkpoint Kinase 1 in the DNA Damage Response Signaling Network. Clinical Cancer Research 2010:16:376-383. 3. Watanabe N et al. Regulation of the Human Wee1hu Cdk Tyrosine 15-Kinase during the Cell-Cycle. Embo Journal 1995:14:1878-1891. 4. Russell P et al. Negative Regulation of Mitosis by Wee1+, a Gene Encoding a Protein-Kinase Homolog. Cell 1987:49:559-567. 5. Masaki T et al. Cyclins and cyclin-dependent kinases: Comparative study of hepatocellular carcinoma versus cirrhosis. Hepatology 2003:37:534-543. 6. Iorns E et al. Integrated Functional, Gene Expression and Genomic Analysis for the Identification of Cancer Targets. PLOS ONE 2009:4:e5120. 7. Mir SE et al. In Silico Analysis of Kinase Expression Identifies WEE1 as a Gatekeeper against Mitotic Catastrophe in Glioblastoma. Cancer Cell 2010:18:244-257. 8. Wang YL et al. Radiosensitization of p53 mutant cells by PD0166285, a novel G(2) checkpoint abrogator. Cancer Research 2001:61:8211-8217. 9. Hirai H et al. Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents. Molecular Cancer Therapeutics 2009:8:2992-3000. 10. Hirai H et al. MK-1775, a small molecule Wee1 inhibitor, enhances antitumor efficacy of various DNA-damaging agents, including 5-fluorouracil. Cancer Biology & Therapy 2010:9:514-522. 11. Rajeshkumar NV et al. MK-1775, a Potent Wee1 Inhibitor, Synergizes with Gemcitabine to Achieve Tumor Regressions, Selectively in p53-Deficient Pancreatic Cancer Xenografts. Clinical Cancer Research 2011:17:2799-2806. 12. Sorensen CS et al. Safeguarding genome integrity: the checkpoint kinases ATR, CHK1 and WEE1 restrain CDK activity during normal DNA replication. Nucleic Acids Research 2012:40:477-486. 13. Martin Y et al. Novel insights into maintaining genomic integrity: Wee1 regulating Mus81/Eme1. Cell Division 2011:6.  
14. Beck H et al. Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase. Journal of Cell Biology 2010:188:629-638. 15. Kreahling JM et al. MK1775, a Selective Wee1 Inhibitor, Shows Single-Agent Antitumor Activity against Sarcoma Cells. Molecular Cancer Therapeutics 2012:11:174-182. 16. Do K et al. Phase I Study of Single-Agent AZD1775 (MK-1775), a Wee1 Kinase Inhibitor, in Patients With Refractory Solid Tumors. Journal of Clinical Oncology 2015:33:3409-+. 17. Leijen S et al. Phase I Study Evaluating WEE1 Inhibitor AZD1775 As Monotherapy and in Combination With Gemcitabine, Cisplatin, or Carboplatin in Patients With Advanced Solid Tumors. Journal of Clinical Oncology 2016:34:4371-4380. 18. Leijen S et al. Phase II Study of WEE1 Inhibitor AZD1775 Plus Carboplatin in Patients With TP53-Mutated Ovarian Cancer Refractory or Resistant to First-Line Therapy Within 3 Months. Journal of Clinical Oncology 2016:34:4354-+. 19. Hamilton DH et al. WEE1 Inhibition Alleviates Resistance to Immune Attack of Tumor Cells Undergoing Epithelial-Mesenchymal Transition. Cancer Research 2014:74:2510-2519. 20. Bindea G et al. Natural immunity to cancer in humans. Current Opinion in Immunology 2010:22:215-222. 21. Galon J et al. Cancer classification using the Immunoscore: a worldwide task force. Journal of Translational Medicine 2012:10.  
22. al. SLe: TNM classification of malignant tumours, 7th edition. Chichester, West Sussex, UK; Hoboken, NJ, Wiley-Blackwell, 2010 pp. 309 23. Galon J et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006:313:1960-1964. 24. Mlecnik B et al. Histopathologic-Based Prognostic Factors of Colorectal Cancers Are Associated With the State of the Local Immune Reaction. Journal of Clinical Oncology 2011:29:610-618. 25. Pages F et al. In Situ Cytotoxic and Memory T Cells Predict Outcome in Patients With Early-Stage Colorectal Cancer. Journal of Clinical Oncology 2009:27:5944-5951. 26. Kalluri R et al. The basics of epithelial-mesenchymal transition. Journal of Clinical Investigation 2009:119:1420-1428. 27. Sanders DSA et al. Alterations in cadherin and catenin expression during the biological progression of melanocytic tumours. Journal of Clinical Pathology-Molecular Pathology 1999:52:151-157. 28. Laing N et al. Abstract 337: Genetic analysis of tumors from a phase II trial evaluating AZD1775, carboplatin and paclitaxel in patients with TP53-mutant ovarian cancer. Cancer Research 2016:76:337-337. 29. Bauer TM et al. Abstract CT013: A phase Ib, open-label, multicenter study to assess the safety, tolerability, pharmacokinetics, and antitumor activity of AZD1775 monotherapy in patients with advanced solid tumors: initial findings. Cancer Research 2016:76:CT013-CT013. 30. Pfister Sophia X et al. Inhibiting WEE1 Selectively Kills Histone H3K36me3-Deficient Cancers by dNTP Starvation. Cancer Cell 28:557-568. 31. Dressler LG et al. How Will GINA Influence Participation in Pharmacogenomics Research and Clinical Testing? Clin Pharmacol Ther 2009:86:472-475. 32. Kass NE et al. Medical privacy and the disclosure of personal medical information: The beliefs and experiences of those with genetic and other clinical conditions. American Journal of Medical Genetics Part A 2004:128A:261-270. 33. Tabor HK et al. Genomics really gets personal: How exome and whole genome sequencing challenge the ethical framework of human genetics research. American Journal of Medical Genetics Part A 2012:155:2916-2924. 34. Berg JS et al. Deploying whole genome sequencing in clinical practice and public health: Meeting the challenge one bin at a time. Genet Med 2011:13:499-504. 35. Caulfield T et al. Research Ethics Recommendations for Whole-Genome Research: Consensus Statement. PLoS Biol 2008:6:e73.  
| ECOG Performance Status Scale                                                                                                                                                               | Karnofsky Performance Scale                     |                                                            |             |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------|------------------------------------------------------------|-------------|
| Grade                                                                                                                                                                                       | Descriptions                                    | Percent                                                    | Description |
| 100                                                                                                                                                                                         | Normal, no complaints, no  evidence of disease. |                                                            |             |
| Normal activity. Fully active,  able to carry on all pre-disease  performance without  restriction.                                                                                         |                                                 |                                                            |             |
| 0                                                                                                                                                                                           | Able to carry on normal activity;               |                                                            |             |
| 90                                                                                                                                                                                          | minor 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). | Normal activity with effort;                    |                                                            |             |
| 80                                                                                                                                                                                          | some signs or symptoms of  disease.             |                                                            |             |
| 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                                                                                                                                                                                           | Requires considerable assistance                |                                                            |             |
| 50                                                                                                                                                                                          | and frequent medical care.                      |                                                            |             |
| In bed >50% of the time.  Capable of only limited selfcare, confined to bed or chair  more than 50% of waking  hours.                                                                                                                                                                                             | 40                                              | Disabled, requires special care  and assistance.           |             |
| 3                                                                                                                                                                                           | Severely disabled,                              |                                                            |             |
| 30                                                                                                                                                                                          | hospitalization indicated. Death  not imminent. |                                                            |             |
| 100% bedridden. Completely  disabled. Cannot carry on any  self-care. Totally confined to  bed or chair.                                                                                    | 20                                              | Very sick, hospitalization  indicated. Death not imminent. |             |
| 4                                                                                                                                                                                           | 10                                              | Moribund, fatal processes  progressing rapidly.            |             |
| 5                                                                                                                                                                                           | Dead.                                           | 0                                                          | Dead.       |
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1. appendix a performance status

|  NSC : D - 754352/2
Report Date :Februa             |              |                |               |                   |
|-------------|--------------|----------------|---------------|-------------------|
| a Ca        | ental Therap | Units :Mola    | SPL:U49P      | EXP. ID :1101NS88 |
| Mean Ocaphy | Fry 01, 2012 | Test Date : Jo | lary 18, 2011 |                   |
|             | a            | V V I V        |               |                   |
| 138         |              |                |               |                   |
| 23          |              |                |               |                   |
|             |              |                |               |                   |
| CO          |              |                |               |                   |
| s           |              |                |               |                   |
| 1. In       |              |                |               |                   |
| 97          |              |                |               |                   |
| M           | 18           |                |               |                   |
| 5           |              |                |               |                   |
| 57          |              |                |               |                   |
|             | 1.           | e              |               |                   |
| fe          |              |                |               |                   |
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2. appendix b azd1775 (mk-1775)

CTEP \# 9350
Clinical Center \# 13-C-0032  
  
Clinical Center \# 13-C-0032  
  
Clinical Center \# 13-C-0032  
  
Clinical Center # 13-C-0032
4. appendix d patient's medication
instructions

1. Complete one form for each cycle of treatment. 2. Swallow each capsule whole with a full glass of water either 2 hours before or 2 hours after a meal. Do not chew or open the capsules. If capsule is broken and the powder of the capsules gets on skin, wash the exposed area with as much water as necessary. Inform investigator or nurse if that occurs.  
3. Record the date and time you took the capsule. The boxes in gray reflect times when you should not be taking drug.  
4. If you have any comments or notice any side effects, please record them in the Comments column. 5. Please bring this form and your bottle of AZD1775 when you return for your Day 21 appointment. 6. In case of errors, please place a single slash mark through the error and initial it. Please do not white out any error or scribble it out with ink. Please do not write the correct information directly over the error, but on a separate line next to the error.  
Clinical Center \# 13-C-0032 Today's Date Cycle \#
Dose mg x5/week Patient Name
(initials acceptable)
Patient Study ID  
| DL1 and DL-1 of AZD1775 only   |                         |              |                          |          |
|--------------------------------|-------------------------|--------------|--------------------------|----------|
| Day                            | Date                    | Time of dose | Number of Capsules Taken | Comments |
| PM                             | 100 mg                  | 200 mg       |                          |          |
| AM                             | 25 mg                   |              |                          |          |
| 1                              |                         |              |                          |          |
| 2                              |                         |              |                          |          |
| 3                              |                         |              |                          |          |
| 4                              |                         |              |                          |          |
| 5                              |                         |              |                          |          |
| 6                              |                         |              |                          |          |
| 7                              |                         |              |                          |          |
| 8                              |                         |              |                          |          |
| 9                              | time the content of the |              |                          |          |
| 10                             |                         |              |                          |          |
| 11                             |                         |              |                          |          |
| 12                             |                         |              |                          |          |
| 13                             |                         |              |                          |          |
| 14                             |                         |              |                          |          |
| 15                             |                         |              |                          |          |
| 16                             |                         |              |                          |          |
| 17                             |                         |              |                          |          |
| 18                             | time the content of the |              |                          |          |
| 19                             | time the content of the |              |                          |          |
| 20                             |                         |              |                          |          |
| 21                             |                         |              |                          |          |
appendix d - patient's medication
instructions

INSTRUCTIONS 1. Complete one form for each cycle of treatment. 2. Swallow each capsule whole with a full glass of water either 2 hours before or 2 hours after a meal. Do not chew or open the capsules. If capsule is broken and the powder of the capsules gets on skin, wash the exposed area with as much water as necessary. Inform investigator or nurse if that occurs.  
3. Record the date and time you took the capsule. The boxes in gray reflect times when you should not be taking drug.  
4. If you have any comments or notice any side effects, please record them in the Comments column. 5. Please bring this form and your bottle of AZD1775 when you return for your Day 21 appointment. 6. In case of errors, please place a single slash mark through the error and initial it. Please do not white out any error or scribble it out with ink. Please do not write the correct information directly over the error, but on a separate line next to the error.  
Clinical Center \# 13-C-0032 Today's Date Patient Name
(initials acceptable)
Cycle \#
Dose 225 mg x 10 doses/2 weeks Patient Study ID  
| DL2 of AZD1775 and Higher                                       |    |       |        |        |
|-----------------------------------------------------------------|----|-------|--------|--------|
| Day | Date | Time of dose | Number of Capsules Taken | Comments |    |       |        |        |
| AM                                                              | PM | 25 mg | 100 mg | 200 mg |
| 1                                                               |    |       |        |        |
| 3 2                                                             |    |       |        |        |
| 4                                                               |    |       |        |        |
| 5                                                               |    |       |        |        |
| 6                                                               |    |       |        |        |
| 7                                                               |    |       |        |        |
| 8                                                               |    |       |        |        |
| 9                                                               |    |       |        |        |
| 10                                                              |    |       |        |        |
| 11                                                              |    |       |        |        |
| 12                                                              |    |       |        |        |
| 13                                                              |    |       |        |        |
| 14                                                              |    |       |        |        |
| 15                                                              |    |       |        |        |
| 16                                                              |    |       |        |        |
| 17                                                              |    |       |        |        |
| 18                                                              |    |       |        |        |
| 19                                                              |    |       |        |        |
| 20                                                              |    |       |        |        |
| 21                                                              |    |       |        |        |  
Patient's signature:
appendix d - patient's medication
arm b

INSTRUCTIONS 1. Complete one form for each cycle of treatment. 2. Swallow each capsule whole with a full glass of water either 2 hours before or 2 hours after a meal. Do not chew or open the capsules. If capsule is broken and the powder of the capsules gets on skin, wash the exposed area with as much water as necessary. Inform investigator or nurse if that occurs.  
3. Record the date and time you took the capsule. The boxes in gray reflect times when you should not be taking drug.  
4. If you have any comments or notice any side effects, please record them in the Comments column. 5. Please bring this form and your bottle of AZD1775 when you return for your Day 21 appointment. 6. In case of errors, please place a single slash mark through the error and initial it. Please do not white out any error or scribble it out with ink. Please do not write the correct information directly over the error, but on a separate line next to the error.  
Clinical Center \# 13-C-0032 Today's Date Patient Name
(initials acceptable)
Cycle \#
Patient Study ID  
| Arm B - AZD1775           |                                     |
|---------------------------|-------------------------------------|
| Day   Date   Time of dose | Number of Capsules Taken | Comments |
| 25 mg                     | 100 mg 200 mg                       |
| 1                         |                                     |
| 3                         |                                     |
| 5                         |                                     |
| 6                         |                                     |
| 7                         |                                     |
| 8                         |                                     |
| 9                         |                                     |
| 10                        |                                     |
| 11                        |                                     |
| 12                        |                                     |
| 13                        |                                     |
| 14                        |                                     |
| 15                        |                                     |
| 16                        |                                     |
| 17                        |                                     |
| 18                        |                                     |
| 19                        |                                     |
| 20                        |                                     |
| 21                        |                                     |  
Clinical Center \# 13-C-0032
5. appendix e information on
arm b

Information for Patients, Their Caregivers, and Non-Study Healthcare Team on Possible Interactions with Other Drugs and Herbal Supplements The patient is enrolled on a clinical trial using the experimental study drug AZD1775 (formerly known as MK-1775).  This clinical trial is sponsored by the National Cancer Institute.  This form is addressed to the patient, but includes important information for others who care for this patient.  
These are the things that you as a prescriber need to know:  
 To the patient: Take this paper with you to your medical appointments and keep the attached information card in your wallet.  
AZD1775 may interact with other drugs which can cause side effects.  For this reason, it is very important to tell your study doctors of any medicines you are taking before you enroll onto this clinical trial.  It is also very important to tell your doctors if you stop taking any regular medicines, or if you start taking a new medicine while you take part in this study.  When you talk about your current medications with your doctors, include medicine you buy without a prescription (over-the-counter remedy), or herbal supplements such as St. John's Wort.  It is helpful to bring your medication bottles or an updated medication list with you.  
Many health care providers can write prescriptions.  You must tell all of your health care providers (doctors, physician assistants, nurse practitioners, or pharmacists) you are taking part in a clinical trial.  
These are the things that you and they need to know:
AZD1775 must be used very carefully with other medicines that need certain liver enzymes or transport proteins to be effective or to be cleared from your system.  Before you enroll onto the clinical trial, your study doctor will work with your regular health care providers to review Clinical Center \# 13-C-0032
5. appendix e information on
any medicines and herbal supplements

Please be very careful!  Over-the-counter drugs (including herbal supplements) may
.  
contain ingredients that could interact with your study drug.  Speak to your doctors or pharmacist to determine if there could be any side effects.  
Your regular health care provider should check a frequently updated medical reference or
•
call your study doctor before prescribing any new medicine or discontinuing any medicine.  Your study doctor's name is and he or she can be contacted at February 2017
5. appendix e information on
study drug information wallet card

You are enrolled on a clinical trial using the experimental study drug AZD1775. This clinical trial is sponsored by the NCI. AZD1775 may interact with drugs that are processed by your liver, or use certain transport proteins in your body.  Because of this, it is very important to:
 Tell your doctors if you stop taking any medicines or if you start taking any new medicines.  
▷ Tell all of your health care providers (doctors, physician assistants, nurse practitioners, or pharmacists) that you are taking part in a clinical trial.  
▷ Check with your doctor or pharmacist whenever you need to use an over-the-counter medicine or herbal supplement.  
  
AZD1775 interacts with CYP 3A4, 2C19, OATP1B1, OATP1B3, MATE1, MATE2K, P-gp, and BCRP and must be used very carefully with other medicines that interact with these enzymes and proteins.
5. appendix e information on
6. appendix f pk/pd collection

Clinical Center \# 13-C-0032  
| Date:                                                                 | PK/PD SAMPLE COLLECTION SHEET ARM B: Cycle 1 Day 1   |                                               |                                         |
|-----------------------------------------------------------------------|------------------------------------------------------|-----------------------------------------------|-----------------------------------------|
| CTEP Protocol P9350                                                   | Ht:                                                  | Research Nurse:                               |                                         |
| Page                                                                  | for                                                  | Phone:                                        |                                         |
| Sample Pick-up                                                        |                                                      |                                               |                                         |
| Dose level:                                                           | Dose AZD1775:                                        | Wt:                                           | Pager:                                  |
| Lab phone: 301-451-1169                                               |                                                      |                                               |                                         |
| Patient ID:                                                           | BSA:                                                 | PI: A. P. Chen, MD                            |                                         |
| ***PK SAMPLES GO ON ICE*****                                          | Phone: 301-768-2749                                  |                                               |                                         |
| PLEASE LABEL EACH TUBE WITH ACTUAL DATE AND TIME OF SAMPLE COLLECTION |                                                      |                                               |                                         |
| Ideal                                                                 | Actual                                               | Record comments (i.e., if collection missed), |                                         |
| Day                                                                   | Time                                                 | Instructions                                  | and sign each time you collect a sample |
| Time                                                                  | Time                                                 |                                               |                                         |
| Prior to                                                              | PK 200 EDTA (lavender top) 6 mL                      |                                               |                                         |
| AZD1775                                                               | Label tube: drug, draw date and time                 |                                               |                                         |
| Day 1                                                                 | administration                                       | PLACE ON ICE                                  |                                         |
| Prior to                                                              | PD 300 1x 6 mL NaHep Label tube:                     |                                               |                                         |
| AZD1775                                                               |                                                      |                                               |                                         |
| Day 1                                                                 | drug, draw date and time Room                        |                                               |                                         |
| administration                                                        | temperature                                          |                                               |                                         |
| PD 400 2 x 4 mL EDTA Label                                            |                                                      |                                               |                                         |
| Prior to                                                              |                                                      |                                               |                                         |
| Day 1                                                                 | AZD1775                                              | tubes: drug, draw date and time               |                                         |
| administration                                                        | Room temperature                                     |                                               |                                         |
| Prior to                                                              | PD 800 1x 7 mL SST Label tube:                       |                                               |                                         |
| Day 1                                                                 | AZD1775                                              | drug, draw date and time Room                 |                                         |
| administration                                                        | temperature                                          | Administer AZD1775, Time:                     |                                         |
| PK 201 EDTA (lavender top) 6 mL                                       |                                                      |                                               |                                         |
| 2 hours after                                                         |                                                      |                                               |                                         |
| Day 1                                                                 | Label tube: drug, draw date and time                 |                                               |                                         |
| dose                                                                  | PLACE ON ICE                                         |                                               |                                         |
| PK 202 EDTA (lavender top) 6 mL                                       |                                                      |                                               |                                         |
| 4 hours after                                                         | Label tube: drug, draw date and time                 |                                               |                                         |
| Day 1                                                                 | dose                                                 | PLACE ON ICE                                  |                                         |  
Clinical Center \# 13-C-0032  
| Date:                                                                 | PK/PD SAMPLE COLLECTION SHEET ARM B Cycle 1 Day 4   |                                                   |        |                                     |
|-----------------------------------------------------------------------|-----------------------------------------------------|---------------------------------------------------|--------|-------------------------------------|
| CTEP Protocol P9350                                                   | Ht:                                                 | Research Nurse:                                   |        |                                     |
| Page                                                                  | Phone:                                              |                                                   |        |                                     |
| for Sample Pick-up                                                    |                                                     |                                                   |        |                                     |
| Dose level:                                                           | Dose AZD1775:                                       | Wt:                                               | Pager: |                                     |
| Lab phone: 301-451-1169                                               |                                                     |                                                   |        |                                     |
| Patient ID:                                                           | BSA:                                                | PI: A. P. Chen, MD                                |        |                                     |
| **                                                                    | Phone: 301 768-2749                                 |                                                   |        |                                     |
| PLEASE LABEL EACH TUBE WITH ACTUAL DATE AND TIME OF SAMPLE COLLECTION |                                                     |                                                   |        |                                     |
| Ideal                                                                 | Actual                                              | Record comments (i.e., if collection missed), and |        |                                     |
| Day                                                                   | Time                                                | Instructions                                      | Time   | sign each time you collect a sample |
| Time                                                                  |                                                     |                                                   |        |                                     |
| PD 401 2 x 4 mL EDTA Label                                            |                                                     |                                                   |        |                                     |
| 4 ± 1 hours                                                           |                                                     |                                                   |        |                                     |
| Day 4                                                                 | tubes: drug, draw date and time                     |                                                   |        |                                     |
| after dose                                                            | Room temperature                                    | Administer AZD1775, Time:                         |        |                                     |  
Clinical Center \# 13-C-0032  
| Date:                                                                 | PK/PD SAMPLE COLLECTION SHEET ARM B Cycle 1 Day 8   |                                                   |        |      |                                     |
|-----------------------------------------------------------------------|-----------------------------------------------------|---------------------------------------------------|--------|------|-------------------------------------|
| CTEP Protocol P9350                                                   | Ht:                                                 | Research Nurse:                                   |        |      |                                     |
| Page                                                                  | Phone:                                              |                                                   |        |      |                                     |
| for Sample Pick-up                                                    |                                                     |                                                   |        |      |                                     |
| Dose level:                                                           | Dose AZD1775:                                       | Wt:                                               | Pager: |      |                                     |
| Lab phone: 301-451-1169                                               |                                                     |                                                   |        |      |                                     |
| Patient ID:                                                           | BSA:                                                | PI: A. P. Chen, MD                                |        |      |                                     |
| **                                                                    | Phone: 301 768-2749                                 |                                                   |        |      |                                     |
| PLEASE LABEL EACH TUBE WITH ACTUAL DATE AND TIME OF SAMPLE COLLECTION |                                                     |                                                   |        |      |                                     |
| Ideal                                                                 | Actual                                              | Record comments (i.e., if collection missed), and |        |      |                                     |
| Day                                                                   | Time                                                | Instructions                                      | Time   | Time | sign each time you collect a sample |
| Prior to                                                              | PK 203 EDTA (lavender top) 6 mL                     |                                                   |        |      |                                     |
| Day 8                                                                 | AZD1775                                             | Label tube: drug, draw date and                   |        |      |                                     |
| administration                                                        | time PLACE ON ICE                                   |                                                   |        |      |                                     |
| Prior to                                                              | PD 402 2 x 4 mL EDTA Label                          |                                                   |        |      |                                     |
| Day 8                                                                 | AZD1775                                             | tubes: drug, draw date and time                   |        |      |                                     |
| administration                                                        | Room temperature                                    |                                                   |        |      |                                     |
| Prior to                                                              | PD 301 1x 6 mL NaHep Label                          |                                                   |        |      |                                     |
| Day 8                                                                 | AZD1775                                             | tube: drug, draw date and time                    |        |      |                                     |
| aministration                                                         | Room temperature                                    |                                                   |        |      |                                     |
| Prior to                                                              | PD 801 1x 7 mL SST Label tubes:                     |                                                   |        |      |                                     |
| Day 8                                                                 | AZD1775                                             | drug, draw date and time Room                     |        |      |                                     |
| aministration                                                         | temperature                                         |                                                   |        |      |                                     |
| PD 403 2 x 4 mL EDTA Label                                            |                                                     |                                                   |        |      |                                     |
| 4 ± 1 hours                                                           |                                                     |                                                   |        |      |                                     |
| Day 8                                                                 | tubes: drug, draw date and time                     |                                                   |        |      |                                     |
| after dose                                                            | Room temperature                                    | Administer AZD1775, Time:                         |        |      |                                     |  
Clinical Center \# 13-C-0032  
| Date:                                                                 | PK/PD SAMPLE COLLECTION SHEET ARM B Cycle 1 Day 11   |                                                   |                         |        |                                     |
|-----------------------------------------------------------------------|------------------------------------------------------|---------------------------------------------------|-------------------------|--------|-------------------------------------|
| CTEP Protocol P9350                                                   | Research Nurse:                                      |                                                   |                         |        |                                     |
| Ht:                                                                   | Page                                                 | Phone:                                            |                         |        |                                     |
| for Sample Pick-up                                                    |                                                      |                                                   |                         |        |                                     |
| Dose level:                                                           | Dose AZD1775:                                        | Wt:                                               | Lab phone: 301-451-1169 | Pager: |                                     |
| Patient ID:                                                           | BSA:                                                 | PI: A. P. Chen, MD                                |                         |        |                                     |
| ****PK SAMPLES GO ON ICE*****                                         | Phone: 301 768-2749                                  |                                                   |                         |        |                                     |
| PLEASE LABEL EACH TUBE WITH ACTUAL DATE AND TIME OF SAMPLE COLLECTION |                                                      |                                                   |                         |        |                                     |
| Ideal                                                                 | Actual                                               | Record comments (i.e., if collection missed), and |                         |        |                                     |
| Day                                                                   | Time                                                 | Instructions                                      | Time                    | Time   | sign each time you collect a sample |
| PD 404 2 x 4 mL EDTA Label                                            |                                                      |                                                   |                         |        |                                     |
| 4 ± 1 hours                                                           |                                                      |                                                   |                         |        |                                     |
| Day 11                                                                | tubes: drug, draw date and time                      |                                                   |                         |        |                                     |
| after dose                                                            | Room temperature                                     | Administer AZD1775, Time:                         |                         |        |                                     |  
Clinical Center \# 13-C-0032
**CTC samples collected at each cycle.  Sample numbering to be consecutive starting from PD 405 and included below.  
| PD SAMPLE COLLECTION SHEET ARM B Cycle                                |                             |                                                   |        |                                     |
|-----------------------------------------------------------------------|-----------------------------|---------------------------------------------------|--------|-------------------------------------|
| Date:                                                                 | Day 1                       |                                                   |        |                                     |
| CTEP Protocol P9350                                                   | Ht:                         | Research Nurse:                                   |        |                                     |
| Page                                                                  | Phone:                      |                                                   |        |                                     |
| for Sample Pick-up                                                    |                             |                                                   |        |                                     |
| Dose level:                                                           | Dose AZD1775:               | Wt:                                               | Pager: |                                     |
| Lab phone: 301-451-1169                                               |                             |                                                   |        |                                     |
| Patient ID:                                                           | BSA:                        | PI: A. P. Chen, MD                                |        |                                     |
| Phone: 301 768-2749                                                   |                             |                                                   |        |                                     |
| PLEASE LABEL EACH TUBE WITH ACTUAL DATE AND TIME OF SAMPLE COLLECTION |                             |                                                   |        |                                     |
| Ideal                                                                 | Actual                      | Record comments (i.e., if collection missed), and |        |                                     |
| Day                                                                   | Time                        | Instructions                                      | Time   | sign each time you collect a sample |
| Time                                                                  |                             |                                                   |        |                                     |
| Prior to                                                              | PD 40   2 x 4 mL EDTA Label |                                                   |        |                                     |
| Day 1                                                                 | AZD1775                     | tubes: drug, draw date and time                   |        |                                     |
| aministration                                                         | Room temperature            | Administer AZD1775, Time:                         |        |                                     |  
Clinical Center \# 13-C-0032
**CTC samples collected at each cycle.  Sample numbering to be consecutive from previous specimen and included below.  
| Date:                                                                 | PD SAMPLE COLLECTION SHEET ARM B Cycle   | Day 4                                             |        |      |                                     |
|-----------------------------------------------------------------------|------------------------------------------|---------------------------------------------------|--------|------|-------------------------------------|
| CTEP Protocol P9350                                                   | Ht:                                      | Research Nurse:                                   |        |      |                                     |
| Page                                                                  | Phone:                                   |                                                   |        |      |                                     |
| for Sample Pick-up                                                    |                                          |                                                   |        |      |                                     |
| Dose level:                                                           | Dose AZD1775:                            | Wt:                                               | Pager: |      |                                     |
| Lab phone: 301-451-1169                                               |                                          |                                                   |        |      |                                     |
| Patient ID:                                                           | BSA:                                     | PI: A. P. Chen, MD                                |        |      |                                     |
| Phone: 301 768-2749                                                   |                                          |                                                   |        |      |                                     |
| PLEASE LABEL EACH TUBE WITH ACTUAL DATE AND TIME OF SAMPLE COLLECTION |                                          |                                                   |        |      |                                     |
| Ideal                                                                 | Actual.                                  | Record comments (i.e., if collection missed), and |        |      |                                     |
| Day                                                                   | Time                                     | Instructions                                      | Time   | Time | sign each time you collect a sample |
| PD 40_2 x 4 mL EDTA Label                                             |                                          |                                                   |        |      |                                     |
| 4 ± 1 hours                                                           |                                          |                                                   |        |      |                                     |
| Day 4                                                                 | tubes: drug, draw date and time          |                                                   |        |      |                                     |
| after dose                                                            | Room temperature                         | Administer AZD1775, Time:                         |        |      |                                     |  
Clinical Center \# 13-C-0032
**CTC samples collected at each cycle.  Sample numbering to be consecutive from previous specimen and included below.  
| PD SAMPLE COLLECTION SHEET ARM B Cycle                                |                                 |                                                   |        |      |                                     |
|-----------------------------------------------------------------------|---------------------------------|---------------------------------------------------|--------|------|-------------------------------------|
| Date:                                                                 | Day 8                           |                                                   |        |      |                                     |
| CTEP Protocol P9350                                                   | Ht:                             | Research Nurse:                                   |        |      |                                     |
| Page                                                                  | Phone:                          |                                                   |        |      |                                     |
| for Sample Pick-up                                                    |                                 |                                                   |        |      |                                     |
| Dose level:                                                           | Dose AZD1775:                   | Wt:                                               | Pager: |      |                                     |
| Lab phone: 301-451-1169                                               |                                 |                                                   |        |      |                                     |
| Patient ID:                                                           | BSA:                            | PI: A. P. Chen, MD                                |        |      |                                     |
| Phone: 301 768-2749                                                   |                                 |                                                   |        |      |                                     |
| PLEASE LABEL EACH TUBE WITH ACTUAL DATE AND TIME OF SAMPLE COLLECTION |                                 |                                                   |        |      |                                     |
| Ideal                                                                 | Actual                          | Record comments (i.e., if collection missed), and |        |      |                                     |
| Day                                                                   | Time                            | Instructions                                      | Time   | Time | sign each time you collect a sample |
| Prior to                                                              | PD 40   2 x 4 mL EDTA Label     |                                                   |        |      |                                     |
| Day 8                                                                 | AZD1775                         | tubes: drug, draw date and time                   |        |      |                                     |
| aministration                                                         | Room temperature                |                                                   |        |      |                                     |
| PD 40  2 x 4 mL EDTA Label                                            |                                 |                                                   |        |      |                                     |
| 4 ± 1 hours                                                           |                                 |                                                   |        |      |                                     |
| Day 8                                                                 | tubes: drug, draw date and time |                                                   |        |      |                                     |
| after dose                                                            | Room temperature                | Administer AZD1775, Time:                         |        |      |                                     |  
Clinical Center \# 13-C-0032
**CTC samples collected at each cycle.  Sample numbering to be consecutive from previous specimen and included below.  
| Date:                                                                 | PD SAMPLE COLLECTION SHEET ARM B Cycle   |  Day 11                                           |        |                                     |
|-----------------------------------------------------------------------|------------------------------------------|---------------------------------------------------|--------|-------------------------------------|
| CTEP Protocol P9350                                                   | Ht:                                      | Research Nurse:                                   |        |                                     |
| Page                                                                  | Phone:                                   |                                                   |        |                                     |
| for Sample Pick-up                                                    |                                          |                                                   |        |                                     |
| Dose level:                                                           | Dose AZD1775:                            | Wt:                                               | Pager: |                                     |
| Lab phone: 301-451-1169                                               |                                          |                                                   |        |                                     |
| Patient ID:                                                           | BSA:                                     | PI: A. P. Chen, MD                                |        |                                     |
| Phone: 301 768-2749                                                   |                                          |                                                   |        |                                     |
| PLEASE LABEL EACH TUBE WITH ACTUAL DATE AND TIME OF SAMPLE COLLECTION |                                          |                                                   |        |                                     |
| Ideal                                                                 | Actual                                   | Record comments (i.e., if collection missed), and |        |                                     |
| Day                                                                   | Time                                     | Instructions                                      | Time   | sign each time you collect a sample |
| Time                                                                  |                                          |                                                   |        |                                     |
| PD 40   2 x 4 mL EDTA Label                                           |                                          |                                                   |        |                                     |
| 4 ± 1 hours                                                           |                                          |                                                   |        |                                     |
| Day 11                                                                | tubes: drug, draw date and time          |                                                   |        |                                     |
| after dose                                                            | Room temperature                         | Administer AZD1775, Time:                         |        |                                     |  
Clinical Center \# 13-C-0032
**CTC samples collected at restaging.  Sample numbering to be consecutive from previous specimen and included below.  
| Date:                                                                 | PD SAMPLE COLLECTION SHEET ARM B RESTAGING DATE TBD   |                                                   |                     |      |                                     |
|-----------------------------------------------------------------------|-------------------------------------------------------|---------------------------------------------------|---------------------|------|-------------------------------------|
| CTEP Protocol P9350                                                   | Ht:                                                   | Research Nurse:                                   |                     |      |                                     |
| Page                                                                  | Phone:                                                |                                                   |                     |      |                                     |
| for Sample Pick-up                                                    |                                                       |                                                   |                     |      |                                     |
| Dose level:                                                           | Dose AZD1775:                                         | Wt:                                               | Pager:              |      |                                     |
| Lab phone: 301-451-1169                                               |                                                       |                                                   |                     |      |                                     |
| Patient ID:                                                           | BSA:                                                  | PI: A. P. Chen, MD                                |                     |      |                                     |
| Phone: 301 768-2749                                                   |                                                       |                                                   |                     |      |                                     |
| PLEASE LABEL EACH TUBE WITH ACTUAL DATE AND TIME OF SAMPLE COLLECTION |                                                       |                                                   |                     |      |                                     |
| Ideal.                                                                | Actual                                                | Record comments (i.e., if collection missed), and |                     |      |                                     |
| Day                                                                   | Time                                                  | Instructions                                      | Time                | Time | sign each time you collect a sample |
| restaging                                                             | Prior to                                              | PD 4                                              | 2 x 4 mL EDTA Label |      |                                     |
| (fter                                                                 | AZD1775                                               | tubes: drug, draw date and time                   |                     |      |                                     |
| completion                                                            | administration                                        | Room temperature                                  |                     |      |                                     |
| of Cycle                                                              |                                                       |                                                   |                     |      |                                     |
| Administer AZD1775, Time:                                             |                                                       |                                                   |                     |      |                                     |  
100