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form no. 638 v04.2 ecog

Instructions: **This form is a required part of pathology submission.** Please complete and submit along with all pathology material and corresponding pathology reports requested by the protocol. See list of required materials as specified in EACH protocol.  
ECOG PCO-RL IS FULLY- COMPLIANT WITH DHHS, HIPAA, AND OHRP REGULATIONSTel. 312-503-3384 Fax 312-503-3385  
| Fax 312-503-3385                                                                                                                                |                                                                                               |                                         |                        |                  |
|-------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------|-----------------------------------------|------------------------|------------------|
| PART A: To Be Completed By Data Manager/CRA                                                                                                     | DO NOT USE INITIALS - Submit Patient's FULL Name (The Patient has authorized the use of PHI.) |                                         |                        |                  |
| Date sample sent to ECOG                                                                                                                        | ______/______/_______ (M,D,Y)                                                                 | Patient's Name:                         |                        |                  |
| Data Manager_______________________________________                                                                                             | Last_______________________                                                                   | First ____________________              |                        |                  |
| Address ___________________________________________                                                                                             | ECOG Prot. No. _________                                                                      | ECOG Patient Seq. No. ________          |                        |                  |
| __________________________________________________                                                                                              | Participating Group                                                                           | Participating Group                     |                        |                  |
| Prot. No. _______________                                                                                                                       | Patient ID No.________________                                                                |                                         |                        |                  |
| Telephone No. (                                                                                                                                 | ) _______________________________                                                             | Group __________                        | Institution_________   | PI _____________ |
| Fax No. (                                                                                                                                       | ) _____________________________________                                                       | Step No. ________                       | Affiliate _________    |                  |
| Email address ______________________________________                                                                                            | ECOG Parent Prot. No. ________                                                                | Seq. No. ______________                 |                        |                  |
| PART B:                                                                                                                                         | TO BE COMPLETED BY DATA MANAGER/CRA AND SUBMITTING PATHOLOGIST                                | PCO-RL Use Only                         |                        |                  |
| Status*                                                                                                                                         | Collected (M/D/Y)                                                                             | Disease Site                            | Number of              |                  |
| Date Specimen                                                                                                                                   | Specimen ID                                                                                   | Type of                                 | PCO ID                 |                  |
| (See Below)                                                                                                                                     | Slides/Vials                                                                                  | Numbers                                 | Stain                  | Numbers          |
| Complete for Slides/Vials                                                                                                                       | /                                                                                             | /                                       |                        |                  |
| /                                                                                                                                               | /                                                                                             |                                         |                        |                  |
| Status*                                                                                                                                         | Collected (M/D/Y)                                                                             | Disease Site                            | Number of              |                  |
| Date Specimen                                                                                                                                   | Specimen ID  Numbers                                                                          | Fixative                                | PCO ID                 |                  |
| (See Below)                                                                                                                                     | Blocks/Punch                                                                                  | Numbers                                 |                        |                  |
| Complete for Blocks/Punch                                                                                                                       | /                                                                                             | /                                       |                        |                  |
| /                                                                                                                                               | /                                                                                             |                                         |                        |                  |
| *Status: Please identify the clinical status of the sample.  List all that apply: 1. Original diagnostic material 5. Post-surgery biopsy/tissue | Submitting Pathologist _____________________                                                  |                                         |                        |                  |
| 2. AML/MDS diagnosis                                                                                                                            | 6. Relapse/recurrence                                                                         | Telephone No. (                         | ) ____________________ |                  |
| 3. Pre-protocol treatment                                                                                                                       | 7. Remission/response                                                                         |                                         |                        |                  |
| biopsy/tissue                                                                                                                                   | Address ________________________________                                                      |                                         |                        |                  |
| 4. Post-protocol treatment                                                                                                                      | 8. Other, specify: ______________                                                             | _______________________________________ |                        |                  |
| biopsy/tissue                                                                                                                                   | _________________________                                                                     |                                         |                        |                  |
| Did the patient consent to participate in the storage of samples for future research?                                                           | Yes                                                                                           | No                                      |                        |                  |  
MATERIAL RETURN (All materials will be retained by the ECOG PCO unless return is requested here.)
Does the submitting institution's policy require the return of any submitted material (blocks, H&E slides, etc.)? Yes No If so, please indicate which materials must be returned ______________________________________________________________
All materials will be returned to the **submitting pathologist** unless an alternate address is indicated here______________________
If materials were not able to be submitted for this protocol and its correlative studies, please circle the reason for non-submission. Attach a formal letter referencing regulations, policy, and/or other explanation. If possible, include a copy of the policy.  
Federal/State Regulations ____ Hospital/Institutional Policy _____ Insufficient Tissue _____ Other______ (Specify) _________
Pathologist of Investigator's Signature ______________________________________________
(PCO-RL Use Only)
PV _________________________
PART C: **ECOG PATHOLOGY COORDINATING OFFICE USE ONLY**
Date Sample Received at PCO ____/____/____ Date Sent to Reviewer ____/____/____ Date Sent to PI/Central Lab ____/____/_____
Site Compliance %_____________ Name of Reviewer __________________ PI/Central Lab_________________________
PCO Comments: _____________________________________________________________________ Staff Init. _____________
Investigator: Keep a copy for your files and submit original form to the destination specified in protocol. 2/05 A Randomized, Double-Blinded, Placebo-Controlled Phase II Study of Adjuvant Everolimus Following the Resection of Metastatic Pancreatic Neuroendocrine Tumors to the Liver
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appendix ii patient thank you

We ask that the physician use the template contained in this appendix to prepare a letter thanking the patient for enrolling in this trial. The template is intended as a guide and can be downloaded from the ECOG web site at http://www.ecog.org. As this is a personal letter, physicians may elect to further tailor the text to their situation. This small gesture is a part of a broader program being undertaken by ECOG-ACRIN and the NCI to increase awareness of the importance of clinical trials and improve accrual and follow-through. We appreciate your help in this effort.  
[PATIENT NAME] [DATE]
[PATIENT ADDRESS] Dear [PATIENT SALUTATION],
Thank you for agreeing to take part in this important research study. Many questions remain unanswered in cancer. With the participation of people like you in clinical trials, we will improve treatment and quality of life for those with your type of cancer.  
We believe you will receive high quality, complete care. I and my research staff will maintain very close contact with you. This will allow me to provide you with the best care while learning as much as possible to help you and other patients.  
On behalf of *[INSTITUTION]* and the ECOG-ACRIN Cancer Research Group, with the participation of people like you in clinical trials, we thank you again.  
Sincerely,
[PHYSICIAN NAME]
65 A Randomized, Double-Blinded, Placebo-Controlled Phase II Study of Adjuvant Everolimus Following the Resection of Metastatic Pancreatic Neuroendocrine Tumors to the Liver
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appendix iii patient tablet calendar

1. Take your scheduled dose of each tablet as instructed by your doctor.  
2. If you forget, the missed tablets will not be taken if more than six hours late.  
3. Note the time and number of tablets you take each day. If you develop any side effects or symptoms, please record them in the appropriate spot on your calendar. If you take any medications other than everolimus/placebo, note them in the appropriate spot on your calendar.  
4. Please bring the bottle, any leftover tablets, and your tablet calendar to your next clinic visit.  
**Group Version Date: April 21, 2014**
Patient Tablet Calendar Patient ID \#: _______________________ **Drug Name:** Everolimus/Placebo  
Dose: _____________________________ **Cycle#:** ______________________  
| Use the space below to make notes about things you                                                                                                           |                |                      |                           |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------|----------------------|---------------------------|
| would like to tell the doctor (including unusual symptoms  you experience, other medicine you have taken and  anything else you think would be of interest.) |                |                      |                           |
| 1 2  3  4  5  6  7  8  9  10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30                                                                     | Date           | Time  tablets  taken | Number  of tablets  taken |
| DAY                                                                                                                                                          | Month Day Year |                      |                           |
| Additional Notes:                                                                                                                                            |                |                      |                           |  
Patient signature: ________________________ **Date:** ______________________
A Randomized, Double-Blinded, Placebo-Controlled Phase II Study of Adjuvant Everolimus Following the Resection of Metastatic Pancreatic Neuroendocrine Tumors to the Liver
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appendix iv ecog performance status

| PS 0   | Fully active, able to carry on all pre-disease performance without restriction                                                                             |
|--------|------------------------------------------------------------------------------------------------------------------------------------------------------------|
| PS 1   | Restricted in physically strenuous activity but ambulatory and able to carry out  work of a light or sedentary nature e.g., light house work, office work. |
| PS 2   | Ambulatory and capable of all self-care but unable to carry out any work  activities. Up and about more than 50% of waking hours.                          |
| PS 3   | Capable of only limited self-care, confined to bed or chair more than 50% of  waking hours.                                                                |
| PS 4   | Completely disabled. Cannot carry on any self-care. Totally confined to bed or  chair.                                                                     |  
68 A Randomized, Double-Blinded, Placebo-Controlled Phase II Study of Adjuvant Everolimus Following the Resection of Metastatic Pancreatic Neuroendocrine Tumors to the Liver
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appendix v drugs which may

The following is a list of common CYP3A4 inducers and inhibitors which may impact everolimus metabolism. This is NOT a complete list of medications potentially incompatible with everolimus; therefore patient medications must be evaluated closely to determine patient eligibility for this trial.
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list of cyp3a4 inducing agents

Carbamazepine Phenytoin  
Dexamethasone Primidone  
Ethosuximide Progesterone  
Glucocorticoids Rifabutin  
Griseofulvin Rifampin  
Modafinil Rifapentine Naficillin Rofecoxib Nelfinavir St. John's Wort Nevirapine Sulfadimidine Oxcarbazepine Sulfinpyrazone Phenobarbitol Tipranavir Phenylbutazone Troglitazone
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list of cyp3a4 inhibitors

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| Amiodarone                     | Mifepristone   |
|--------------------------------|----------------|
| Cimetidine                     | Nefazodone     |
| Ciprofloxacin                  | Nelfinavir     |
| Clarithromycin                 | Norfloxacin    |
| Delavirdine                    | Norfluoxetine  |
| Diethyl-dithiocarbamate        | Ritonavir      |
| Diltiazem                      | Roxithromycin  |
| Erythromycin                   | Saquinavir     |
| Fluconazole                    | Troleandomycin |
| Fluvoxamine                    | Voriconazole   |
| Gestodene                      | Warfarin       |
| Grapefruit or Grapefruit juice | Amprenavir     |
| Indanvir                       | Atazanavir     |
| Itraconazole                   | Miconazole     |
| Ketoconazole                   | Telithromycin  |
| Mibefradil                     | Verapamil      |  
A Randomized, Double-Blinded, Placebo-Controlled Phase II Study of Adjuvant Everolimus Following the Resection of Metastatic Pancreatic Neuroendocrine Tumors to the Liver
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appendix vi instructions for reporting

All pregnancies and suspected pregnancies (including a positive or inconclusive pregnancy test regardless of age or disease state) of a female patient while she is on Everolimus/placebo, or within 28 days of the patient's last dose of Everolimus/placebo must be reported in an expeditious manner. The outcome of the pregnancy and neonatal status must also be reported.
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how should the pregnancy be

The pregnancy, suspected pregnancy, or positive/inconclusive pregnancy test must be reported via CTEP's Adverse Event Reporting System (CTEP-AERS) (http://ctep.cancer.gov/protocolDevelopment/electronic_applications/adverse_events.htm)
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when does a pregnancy suspected

An initial report must be done within 24 hours of the Investigator's learning of the event, followed by a complete expedited CTEP-AERS report within 5 calendar days of the initial 24-hour report.
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what other information do i

- The pregnancy (fetal exposure) must be reported as a Grade 3 "Pregnancy, puerperium and perinatal conditions - Other (pregnancy)" under the System Organ Class (SOC) "Pregnancy, puerperium and perinatal conditions"
- The pregnancy must be reported within the timeframe specified in the Adverse Event Reporting section of the protocol for a grade 3 event.  
- The start date of the pregnancy should be reported as the calculated date of conception. - The potential risk of exposure of the fetus to the investigational agent(s) or chemotherapy agent(s) should be documented in the "Description of Event" section of the CTEP-AERS report.
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what else do i need

- The Investigator must follow the female patient until completion of the pregnancy and must report the outcome of the pregnancy and neonatal status via CTEP-AERS.  
- The decision on whether an individual female patient can continue protocol treatment will be made by the site physician in collaboration with the study chair and ECOG-ACRIN Operations Office - Boston. Please contact the ECOG-ACRIN Operations Office - Boston to ask for a conference call to be set up with the appropriate individuals.  
- It is recommended the female subject be referred to an obstetrician-gynecologist, preferably one experienced in reproductive toxicity for further evaluation and counseling.
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how should the outcome of

The outcome of a pregnancy should be reported as an amendment to the initial CTEP-AERS report if the outcome occurs on the same cycle of treatment as the pregnancy itself. However, if the outcome of the pregnancy occurred on a subsequent cycle, a new CTEP-AERS report should be initiated reporting the outcome of the pregnancy.
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what constitutes an abnormal outcome?

An abnormal outcome is defined as any pregnancy that results in the birth of a child with persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions (formerly referred to as disabilities), congenital anomalies, or birth defects. For assistance in recording the grade or category of these events, please contact the CTEP AEMD Help Desk at 301-897-7497 or aemd@tech-res.com, for it will need to be discussed on a case by case basis.
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reporting a fetal death

A fetal death is defined in CTCAE as "A disorder characterized by death in utero; failure of the product of conception to show evidence of respiration, heartbeat, or definite movement of a voluntary muscle after expulsion from the uterus, without possibility of resuscitation."
It must be reported via CTEP-AERS as Grade 4 "Pregnancy, puerperium and perinatal conditions - Other (pregnancy loss)" under the System Organ Class (SOC) "Pregnancy, puerperium and perinatal conditions".  
A fetal death should NOT be reported as a Grade 5 event as currently CTEP-AERS recognizes this event as a patient's death.
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reporting a neonatal death

A neonatal death is defined in CTCAE as "A disorder characterized by cessation of life occurring during the first 28 days of life" that is felt by the investigator to be at least possibly due to the investigational agent/intervention. However, for this protocol, any neonatal death that occurs within 28 days of birth, without regard to causality, must be reported via CTEP-AERS AND any infant death after 28 days that is suspected of being related to the in utero exposure to Everolimus/placebo must also be reported via CTEP-AERs . It must be reported via CTEP-AERS as Grade 4 "General disorders and administration - Other
(neonatal loss)"under the System Organ Class (SOC) "General disorder and administration". A neonatal death should NOT be reported as a Grade 5 event as currently CTEP-AERS
recognizes this event as a patient's death.
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additional required forms

When submitting CTEP-AERS reports for pregnancy, pregnancy loss, or neonatal loss, the CTEP 'Pregnancy Information Form' must be completed and faxed along with any additional medical information to CTEP (301-230-0159). This form is available on CTEP's website (http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/PregnancyReportFor m.pdf)
71  
**Group Version Date: April 21, 2014**
A Randomized, Double-Blinded, Placebo-Controlled Phase II Study of Adjuvant Everolimus Following the Resection of Metastatic Pancreatic Neuroendocrine Tumors to the Liver Appendix VII
E2212 Drug Request Form  
| E2212 EVEROLIMUS/PLACEBO DRUG REQUEST FORM                                                                                                                                                                                                                                                                                                                                                                                                                                                              |       |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------|
| Section I (To be completed by the institution) CTEP NCI ID#:  Principal Investigator:  Institution Name:  Institution Pharmacy  Delivery Address:  Pharmacy Contact:  Pharmacy Contact  Telephone Number:  Pharmacy Contact email:  Pharmacy Contact fax:  Shipment Must Reach  Destination By (Please allow    4 business days for delivery): ECOG-ACRIN Patient  Sequence Number:  Blinded Drug ID#:  Initial Order or Resupply:  Quantity of Blister Packs  Order placed by: (print name) Signature: | Date: |
| Section II (To be completed by ECOG-ACRIN Drug Team) IRB Approval:                                                                                                                                                                                                                                                                                                                                                                                                                                      |       |  
IRB Approval: Blinded Drug ID Confirmed:  
Personnel Name: Signature: Date:  
PLEASE EMAIL THIS DRUG REQUEST FORM AS AN ATTACHMENT TO
900.drugorder@jimmy.harvard.edu or by FAX: 617-632-2063 A Randomized, Double-Blinded, Placebo-Controlled Phase II Study of Adjuvant Everolimus Following the Resection of Metastatic Pancreatic Neuroendocrine Tumors to the Liver
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appendix viii hepatitis screening screening

Prior to randomization, the following three categories of patients should be tested for hepatitis B
viral load and serologic markers, that is, HBV-DNA, HBsAg, HBs Ab, and HBc Ab:
- All patients who currently live in (or have lived in) Asia, Africa, Central and South America, Eastern Europe, Spain, Portugal and Greece.  
[http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3-infectious-diseases-related-totravel/hepatitis-b.htm]
- Patients with any of the following risk factors:
- known or suspected past hepatitis B infection,
- blood transfusion(s) prior to 1990, - current or prior IV drug users, - current or prior dialysis,
- household contact with hepatitis B infected patient(s),
- current or prior high-risk sexual activity,
- body piercing or tattoos, - mother known to have hepatitis B - history suggestive of hepatitis B infection, e.g., dark urine, jaundice, right upper quadrant pain.  
- Additional patients at the discretion of the investigator
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screening for hepatitis c

Prior to randomization, patients with any of the following risk factors for hepatitis C should be tested using quantitative RNA-PCR:
- known or suspected past hepatitis C infection (including patients with past interferon
'curative' treatment),
- blood transfusions prior to 1990, - current or prior IV drug users,
- current or prior dialysis,
- household contact of hepatitis C infected patient(s),
- current or prior high-risk sexual activity,
- body piercing or tattoos.
At the discretion of the investigator, additional patients may also be tested for hepatitis C.  
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