CONFIDENTIAL CRA Training Agenda 1 TopicTimePresenter 1 Protocol Amendment 01 & 02...

CONFIDENTIAL

CRA Training Agenda

1

Topic Time Presenter

1Protocol Amendment 01 & 02 Refresher 8:00-8:30pm EST Xui Ming Lee

2ECRF Updates and Common Issues 8:30-9:30pmEST Hema Ahuja / Anton Shklyayev

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E7389-G000-309A Randomized, Open-label, Multicenter,

Phase 3 Study to Compare the Efficacy and Safety of Eribulin with Dacarbazine in Subjects with Soft Tissue Sarcoma.

Protocol Amendment 01 (25May2012)

Revisions are indicated in red text in the slides

Protocol Amendment 02 (08Aug2012)

Revisions are indicated in green text in the slides

Property and Confidential. Copyright 2010 Eisai2

Inclusion Criteria

1. Histologically confirmed diagnosis of soft tissue sarcoma of high or intermediate grade with one of the following histological subtypes:

a. Adipocytic sarcoma, including:

• i. Dedifferentiated

• ii. Myxoid

• iii. Round Cell

• iv. Pleomorphic

b. Leiomyosarcoma• Tumor histology performed at diagnosis will be acceptable for study

entry, although formalin-fixed paraffin embedded tumor blocks and/or representative slides must be available, and provided to the Sponsor for independent histological review. IHR is not required prior to randomization

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2. Documented evidence of advanced (locally recurrent, locally advanced and/or metastatic) adipocytic sarcoma (restricted to subtypes listed in Inclusion 1) or leiomyosarcoma, incurable by surgery or radiotherapy

Inclusion Criteria

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Inclusion Criteria

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Definition of regimens

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Definition of regimens (cont)

One regimen for advanced disease [continued]:

If treatment interrupted for surgery or RT and then resumed with unchanged schedule and components, is one regimen despite the interruption.

Changed version of an original regimen due to toxicity (dose reduction, omission of components, replacement of component for a similar one) is still considered as one regimen.

However if a new component is added, which is dissimilar to any of the originals, the new combination is considered a new regimen.

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Inclusion Criteria

4. Radiographic evidence of disease progression by RECIST criteria on or after the last anti-cancer therapy within the 6 months prior to randomization

5. Presence of measurable disease meeting the following criteria:a. At least one lesion of ≥ 1.0 cm in long-axis diameter for non-

lymph nodes or ≥ 1.5 cm in short-axis diameter for lymph nodes which is serially measurable according to RECIST 1.1 using either computed tomography/magnetic resonance imaging or panoramic and close-up color photography. If there is only one target lesion and it is a non-lymph node, it should have a longest diameter of at least 1.5 cm.

b. Lesions that have had radiotherapy must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion

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6. Eastern Cooperative Oncology Group performance status of 0, 1 or 2

7. Adequate renal function defined as calculated creatinine clearance ≥ 50 mL/min per the Cockroft and Gault formula

8. Adequate bone marrow function, defined as:

a. Absolute neutrophil count ≥ 1,500/mm3 or ≥ 1.5 x 109/L

b. Platelet count ≥ 100,000/mm3 or ≥ 100 x 109/L

c. Hemoglobin ≥ 10g/dL at baseline (blood transfusions, hematopoietic growth factors

and hematinics are allowed during the Prerandomization Phase to correct Hb values

< 10g/dL)

9. Adequate liver function, defined as:

a. Bilirubin ≤ 1.5 times the upper limit of normal except for unconjugated

hyperbilirubinemia of Gilbert’s syndrome

b. Alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase ≤

3 times ULN. For total ALP > 3 times ULN, the ALP liver isoenzyme must be ≤ 3

times ULN

Inclusion Criteria

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10. Female subjects of child-bearing potential must agree to use two forms of highly effective contraception from the last menstrual period prior to randomization, during study treatment, and for 3 months after the final dose of study treatment

• Intrauterine device or system• Condom or occlusive cap with spermicide• Hormonal contraceptive methods • Vasectomized partner with confirmed azoospermia

• If currently abstinent, the subject must agree to use a double barrier method of contraception, i.e. condom and occlusive cap (diaphragm or cervical/vault caps) with spermicide or until they are on two forms of highly effective contraception for at least one menstrual cycle if they become sexually active during study treatment and for 3 months after the final dose of study treatment

Inclusion Criteria

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11. Male subjects and their female partner who are of child-bearing potential must agree to use two forms of highly effective contraception– If currently abstinent, must agree to use a double barrier method of

contraception if they become sexually active, or until they are on two forms of highly effective contraception as described above

12. Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol

13. Males or females aged ≥ 18 years at the time of informed consent

Inclusion Criteria

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Exclusion Criteria

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Exclusion Criteria

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Exclusion Criteria

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Exclusion Criteria

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Exclusion Criteria

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Previous Anti-Cancer Therapy ‘Given As’ Definition added as Protocol Appendix 2

Prior Anti-Cancer Therapy DescriptionRegimen Given As:

Neoadjuvant Treatment that precedes a second modality of treatment (i.e. surgery) with the intent to increase success.

Adjuvant Additional treatment given after surgery and/or radiotherapy with the intent to reduce the risk of relapse.

Maintenance Treatment that is given to help keep cancer from recurring after it has disappeared or responded following the initial therapy.

Therapeutic Given with the intent to treat the existing tumor advanced and/or metastatic disease where the disease is incurable by surgery or radiotherapy.

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‘Given as’ Definition added into Protocol Amendment

Protocol Procedures

Screening and Baseline [No Changes]

ScreeningDay -21 to -2

BaselineDay -1

Day -1 or Cycle 1/Day 1

Predose

Informed Consent

Verify Inclusion/Exclusion

Record Demographic Data

NYHA Class

ECOG

pTNM Staging

Medical/Surgical History

Vital Signs, Weight

Height

Physical Examination

Randomization

19 CONFIDENTIAL

Screening and Baseline (continued)


BaselineDay -1

ECG (recumbent for at least 5mins)

Haematology and Clinical Chemistry

Urinalysis (dipstick)

Pregnancy Test (serum or urine)

Tumor Assessment (CT/MRI/photograph)

(Day -28 to -2)

Bone Scan (or whole body MRI) (Day -42 to -2)

QoL Questionnaires

Concomitant Medication (from Day -30)

AEs/SAEs (from date of consent)

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Screening and Baseline (continued)


BaselineDay -1

Tumor block or slides for independent histological review

Tumor block or slides for PD analysis

Blood sample for Genomic DNA

Blood sample for RNA analysis

Blood sample for PD analysis

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Baseline (Day -1)

• Screening assessments can serve as Baseline assessments if performed within 72 hours prior to randomization on Day -1 or Cycle 1 Day 1.

• Randomization after reconfirming inclusion/exclusion criteria on Day -1 or pre-dose Cycle 1 Day 1.

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Screen Failures (Protocol Section 8.1.1.1)

For screen failure subjects, the reason(s) for screen failure must be recorded in the electronic case report form (eCRF). Subjects that failed Screening can only be rescreened following approval from the Sponsor. The decision will be based upon the reason(s) for the screen failure, for example a self-limiting condition with a low likelihood of recurrence considering the natural history of the condition.

[Note: For requests to re-screen, send Protocol Inquiry Form with details of screen fail and update of patient status to CRA to process as for medical queries]

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Cycle 1 and Cycle 2 [No Changes]

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Cycle 1 Cycle 2

Day 1 Day 8 Day 15 Day 1 Day 8 Day 15

ECOG

Vital Signs, Weight




Blood sample for RNA

Blood sample for PD

QoL Questionnaires

Study Treatment Administration

Tumor Assessment (wk6)

Eribulin: Day 1 and Day 8Dacarbazine: Day 1

Concomitant Medication collected throughoutAEs/SAEs collected throughout

Eribulin: Day 1 and Day 8Dacarbazine: Day 1

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Cycles 1 and 2 - ECG & PK [No Changes]

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Cycle 1 Cycle 2

Day 1 Day 8 Day 1 Day 8

ECG pre-dose (eribulin)

(eribulin)

ECG end of infusion (eribulin)

(eribulin)

(eribulin)

(eribulin)

Cycle 1 Cycle 2

Day 1 Day 8 Day 1 Day 8

PK pre-dose (after ECG)

PK end of infusion (after ECG)

PK 0.5 to 6 hrs post-dose

PK 24 to 120 hrs post-dose

PK – Eribulin arm

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Cycle 3 onwards

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Day 1 Day 8 Day 15

ECOG

Vital Signs (eribulin)

Weight

Physical Examination (eribulin)

ECG (eribulin)


(eribulin)


QoL Questionnaires

Study Treatment Administration (eribulin)

Concomitant Medication collected throughoutAEs/SAEs collected throughout

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Cycle 3 onwards (continued)

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Cycle 3 onwards - ECG

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Both treatment arms Cycle 3& onwards

Day 1

ECG pre-dose

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Cycle 3 onwards - PK

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Protocol Amendment 01 – no PK samples after Cycle 2

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Off-Treatment Visit [No Changes]within 30 days after final dose

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Off-Treatment Visit

ECOG

Vital Signs, Weight


ECG

Haematology and Clinical Chemistry (central lab)


Pregnancy Test

QoL Questionnaires

Concomitant Medication

AEs/SAEs

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Treatment Cycles

• 21 day cycles• Study Visits- +/- 1 day window• Laboratory Assessments may be performed within 24

hours prior to study treatment administration (Cycle 1 Day 8 onwards). +/- 24 hours for the Day 15 blood sample in Cycle 1 and 2

• Whenever possible, patients should be evaluated at approximately the same time of the day (eg morning or afternoon) at each visit. Procedures should be performed in the same order at each visit.

• Treatment continues until disease progression, unacceptable toxicity or withdrawal of consent

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Follow-Up Period Procedures

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Tumor assessment time-points

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CONFIDENTIALConfidentialProperty and Confidential. Copyright 2010 Eisai

Bone Lesions assessment

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ECG timepoints

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PK Sample timepoints – eribulin arm

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Independent Histology Review andPharmacogenomic and Pharmacodynamic Analysis

Independent Histological Review

•Archived Tumor block/slides for independent histological review: mandatory. Local diagnosis used for study entry. Confirm tumor block/slides are available before consenting the patient. Tumor samples to be sent to PPD lab after randomization.

Pharmacogenomic and Pharmacodynamic analysis

•Blood samples for pharmacogenomic and pharmacodynamic analysis and Archived Tumor block/slides for pharmacodynamic analysis: required in the protocol, unless explicitly prohibited by country or regional regulations , or required to be optional by country or regional regulations or IRB/EC requirements.

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Tumor Blocks or Slides for Independent Histological Review (IHR)• The protocol requires that the original histopathological diagnosis

is confirmed by independent histological review (IHR)• For each randomized study subject, pre-study tumor block and/or

slides are required for IHR:• 1st preference:

– 1 x representative formalin-fixed paraffin embedded (FFPE) block AND

– 2 x 4 micron unstained FFPE sections on charged slides from each block of the

diagnostic specimen

• Or 2nd preference if a tumor block is not available to be sent:

– 10 x 4 micron unstained FFPE sections on charged slides from a representative

block AND

– 2 x 4 micron unstained FFPE sections on charged slides from each block of the

diagnostic specimen.

• Each slide must be labeled with the block identifier that it has been taken from

[No Changes]

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Tumor Blocks or Slides for Pharmacodynamic Analysis (PD)

• For each randomized study subject, pre-study tumor block or slides are required for PD analysis:

• 1st preference:

– Most recent FFPE tumor blocks (a sufficient sample to allow

preparation of 10 to 15 sections of 5 microns by the central laboratory)

• Or 2nd preference if a tumor block is not available to be sent:

– 10-15 unstained FFPE sections on charged slides

[No Changes]

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adrenal glands

X

X

1

02 SEP 2009

A B C

label on tumour samplerequisition card sent with tumour sample

IMPORTANT ITEMS TO VERIFY

“Tumour Type” on Requisition card – needs to be the tumour type of the actual sample sent

“Anatomic location of Primary Tumour” on Requisition card – needs to match exactly the “Location of Primary Tumour” in TUM DIAG eCRF panel.

“Drawdate” on sample label should match exactly the “Date of collection” in TUM BIOP eCRF panel. This is the date the tumour sample was taken from subject, not the date the tumour sample was collected from pathology.

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Quality of Life Questionnaires

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Study TreatmentDose and Administration

EribulinSome clarifications in the instructions and dose

delay/reduction instructions presented in a tabulated format for ease of reference

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Eribulin administration

• Treatment schedule:

1.4 mg/m2 of eribulin mesylate administered as an IV bolus or infusion over 2 to 5 minutes on Day 1 and Day 8 of a 21-day cycle

– Eribulin can be given as an IV bolus or diluted in up to 100 mls of

0.9% sodium chloride (NaCl)• Dose calculation:

– Scheduled dose (mg/m2) x body surface area (BSA) (m2) = Dose (mg)

– Each vial contains 1 mg of eribulin mesylate in 2 mL solution

(0.5 mg/mL)

– Dose (mg) x 2 = the number of mL of eribulin to withdraw from vials

for administration

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Clarity added to protocol section 8.4.3.1

Eribulin should only be administered if:

On Cycle 1/Day 1:•All the Inclusion and none of the Exclusion Criteria are met (Sections 8.3.1 and Section 8.3.2)•Correct hypokalaemia and hypomagnesemia prior to initiating treatment with eribulin.

Every Day 1 or Day 8 thereafter:•Absolute Neutrophil Count > 1,000/mm3 or <1.0×109/L•Platelet Count > 75,000/mm3 or <75×109/L•Non-hematologic Toxicity < CTCAE Grade 2, except for inadequately treated nausea and vomiting or both

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Dosing Requirements

Instruction Text 1:

Do NOT Administer Eribulin on Day 1 or Day 8 (or at any other Time) if any of the Following Values are Present

Absolute Neutrophil Count <1,000/mm3 or <1.0×109/L

Platelet Count <75,000/mm3 or <75×109/L

Non-hematologic Toxicity CTCAE Grade 3 or 4

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Dosing Requirements

Instruction Text 2: Permanently Reduce the Dose of Eribulin if any of the Following Values are Present Following the Preceding Dose

Absolute Neutrophil Count <1,000/mm3 or <1.0×109/L with fever and/or infection, or

<500/mm3 or <0.5×109/L for more than 7 days

Platelet Count <50,000/mm3 or <50×109/L requiring blood and/or platelet transfusion, or

<25,000/mm3 or <25×109/L

Non-hematologic Toxicity CTCAE Grade 3 or 4

Day 8 Dose Delay of, or unable to administer Day 8 dose due to treatment‑related toxicity

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Dose Reduction Instructions

Instruction Text 3: Eribulin Dose Reduction Instructions

Eribulin Mesilate Dose

Occurrence of Any Value Requiring Permanent Dose Reduction Whilst Receiving 1.4 mg/m2 of Eribulin Mesilate

1.1 mg/m2


0.7 mg/m2


Permanently discontinue eribulin (Section 8.4.3.4)

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Instructions for subjects who have QTc interval prolongation, or risks thereof, on ECG

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Study TreatmentDose and Administration

Dacarbazine

Dacarbazine Dose

The following dacarbazine starting doses can be selected for each subject in this study:

•Dmax: Dacarbazine 1,200 mg/m2 administered on Day 1 of a 21-day cycle, or

•~85% Dmax: Dacarbazine 1,000 mg/m2 administered on Day 1 of a 21-day cycle, or

•~75% Dmax: Dacarbazine 850 mg/m2 administered on Day 1 of a 21-day cycle

The selection of the starting dose of dacarbazine must be confirmed prior to randomization

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Refer to Protocol Section 8.4.3.2

•Aseptically transfer the required amount of water for injection into the dacarbazine vials and shake until solution is obtained.•Further dilute the solution in 200 to 300 mL (or up to 500mL as per institutional guidelines) of sodium chloride of 5% glucose solution.

•Dacarbazine is administered over 15 to 30 minutes (or up to 60 minutes as per institutional guidelines).

Dacarbazine infusion

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Clarity added to protocol section 8.4.3.2

Dacarbazine should only be administered if:

On Cycle 1/Day 1:•All the Inclusion and none of the Exclusion Criteria are met (Sections 8.3.1 and Section 8.3.2)

Every Day 1 thereafter:•No significant clinical, hematologic or biochemical (specifically liver and kidney) effects are present. Please refer to the dacarbazine prescribing information for specific instructions of use.

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• Refer to prescribing information for details on dose reduction and interruptions for subjects who experience Dacarbazine related toxicity.

Dacarbazine Dose Modifications

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• BSA will be calculated using any method that is accepted and customarily used by the clinical site, such as the Dubois and Dubois, or the Mosteller formula.

• Body Weight Procedures– Height and body weight will be recorded at the Screening. Thereafter,

body weight will be recorded on Day 1 of each treatment cycle for calculation or adjustment of BSA.

Based upon the BSA, the dose of study treatment will be recalculated on Day 1 of each cycle, using the subject's height measured at Screening, and weight measured on Day 1 of each cycle (or up to 24 hours prior to Day 1).

Eribulin :

Recalculation of the BSA prior to the Day 8 dose of each cycle will NOT be required, but is allowed if in accordance with institutional practice.

Body Surface Area: Eribulin, Dacarbazine

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Protocol Section 8.4.3.4 Criteria for Permanent Discontinuation of study treatment

The subject will permanently discontinue study treatment if any of the following criteria are met:

•Unable to administer a scheduled dose of study treatment for more than 21 days for study treatment-related toxicity

•Development of unacceptable toxicity as determined by the PI and/or subject

•Arm A (Eribulin): Treatment-related toxicity requiring a further permanent dose reduction whilst receiving a dose of eribulin mesilate of 0.7 mg/mg2.

•Arm A (Eribulin): Grade 3 or Grade 4 QTc interval prolongation [revision in Protocol Amendment 02 , dated 08Aug2012]

•Arm B (Dacarbazine): Veno-occlusive disease of the liver.

However, if the subject is deemed to have clinical benefit, continuation of study treatment must be discussed with the Sponsor, except for veno-occlusive disease of the liver in Arm B which requires permanent discontinuation of dacarbazine.

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Lost to Follow-Up [No Changes]

Patients will only be considered ‘Lost to Follow-Up’ if:

5 attempted telephone contacts, at least 1 month apart for a period of at least 4 months, with the subject, the subject’s family, or the primary care (family) doctor. The last contact attempt must be at least 4 months after the subject failed to attend a scheduled assessment.

If the last telephone contact is unsuccessful, the site must write a letter with certified proof of posting to the subject, subject’s family, or the primary care (family) doctor to request information on the subject's status.

If all attempts fail to confirm the subject's status, the subject will be considered as ‘lost to follow up’, and this will be recorded in the eCRF.

56 CONFIDENTIAL

eCRF Updates Data Management

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ConfidentialProperty and Confidential. Copyright 2010 Eisai

E7389-G000-309

A Randomized, Open-label, Multicenter, Phase 3 Study to Compare the Efficacy and

Safety of Eribulin with Dacarbazine in Subjects with Soft Tissue Sarcoma.

Data Management

Revisions are indicated in red text in the slides

Property and Confidential. Copyright 2010 Eisai58


Agenda

1. Anti-Cancer Therapy(Anti-Can)Updates2. Previous Therapy(Prev-Thpy)Updates3. Progression History(PROGHX)Updates4. Local Lab –Urinalysis Panel (LCL-Urine) Updates5. Local Lab Hema/Chem Panel6. Amend eCRF Updates7. Vitals 8. Eribulin Updates9. PK/ECG/Dacarbazine scheduled Updates10.Medical History(MHX)11.Conmeds (CM): Blood transfusion12.Lymph Node and Non-Lymph Node Target Lesions13.Non-Target lesions/Time point response14.UNL eCRF/Unscheduled scans/timepoints

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ANTI-CAN: Previous Anti-cancer Therapy

eCRF UpdatesRegimen #’ code list number This was expanded from 6 to 30 for prior regimens Add item# 4 “ Did the patient progress”

Hints and Tips Have the medications for one Regimen split and entered in different rows, else there will be a coding query. For example: if Gemcitabine and Docetaxel are given to the patient as Therapeutic agents. Enter them separately in different rows as shown in screen shot below. If you enter them in one row, Coding will query to split the term for coding purposes

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Correct entries on Anti-Cancer

ANTI-CAN: Previous Anti-cancer Therapy

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PREV THPY: Previous Therapy

eCRF Updatesitem 3 was added and is a required field‘Has the subject received any previous anthracycline therapy for soft tissue sarcoma’Options are ‘Yes’ and ‘No, please clarify if there was a contra-indication’. Free text box is alpha numeric which is to be associated with ‘No…’ radio button option. If Yes then update the MHX eCRF

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PROG HX: Progression History

eCRF Updates

Add entry section now to be used only if progression dates that are not recorded on Anti-cancer therapy eCRF in between regimens

Possible to have duplication of dates on Anti-cancer and Prog-HX

Possible to have dates in Prog-HX which is not present on Anti-Cancer

Hints and Tips

Continue to enter Date of Last Progression as indicated in protocol

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PROG HX: Progression History

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Local Lab - Urinalysis Panel (LCL URIN)

eCRF Updates

Item3 is no longer 'Laboratory name and location', but instead it is 'Dipstick Brand Used'. For the existing data (data which has been entered before the PPC implementation), sites will have to go back to each LCL URIN panel previously entered, and complete item 3. 'Dipstick brand used'. Item will show as incomplete (yellow) until entered. Items 7 to 9 naming of the result labels were modified to accommodate the different methods used to read dipsticks by various labs / sites.

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Local Lab - Urinalysis Panel (LCL URIN)

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Local Lab – Hema/Chem Panel

Hints and Tips If PPD report indicates that the sample is not reported or haemolysed or clotted for certain analytes, complete the missing information using the Local lab report for the same date and visit in the Unscheduled visit

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Lab Report PPD

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Unscheduled Lab

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Enter date on DOV and hit Submit Once done you will see the Unscheduled Tab populated.

Check the forms that you need to enter data for and hit submit at the bottom of the eCRF

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Click on the tabs to complete the forms appropriately

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Amend eCRF

This page must be entered for EVERY patient, including screen failed patients. If the subject was consented under the original protocol, select 'Initial Version‘ If the subject was consented under the amended protocol, select 'New Version' and specify the 'Amendment Number' from the drop-down menu. If the initial subject was later re-consented to the new version of the protocol, click on 'Add Entry' button, specify to which protocol version the subject was re-consented to, as well as the 'Date of Re-consent'.

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Vital Signs

Hints and Tips

Eribulin: Recalculation of the BSA prior to the Day 8 dose of each cycle will NOT be

required, but is allowed if in accordance with institutional practice. If BSA is not calculated on D8 please enter Not done in the item level

comment DO NOT duplicate the same BSA as of D1 in D8 if not calculated on D8.

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eCRF Study Medication - Intravenous(Eribulin)

‘Units of Drug added to IV bag or syringe’ was modified to increase the decimals from 1 to 2 i.e. X.XX. Initial design only accepted after dilution values, but Eribulin is also administered as a bolus injection (non-diluted). We need to capture the undiluted volumes accurately, which will have decimal values.

For the existing data, sites will have to go back to each Eribulin undiluted volumes previously entered, and update. Example, if the actual dose was 2.68 mg, and the site entered 2.7 as a rounded off value due to field limitation, the system automatically added a zero for the second decimal. But 2.70 is not the precise value but 2.68 should be entered.

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Protocol Amendment #1 New PK Schedule

PK samples will no longer be collected past Cycle 2. Therefore the panels which are currently present in C5D8, C8D8 should not be available for subjects consented under the amended protocol.

patients which were initially consented under the original protocol, as well as patients which were re-consented under the amended protocol while on study, will retain the PK-Sample panel in visits past Cycle 2.

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Protocol Amendment #1 New ECG Schedule

ECG will now be conducted on Cycle 3 and all subsequent cycles at Day 8 for Arm A patients only.

Cycle 1 and Cycle 2 structure remains the same. ECG-PS panel is now available for: C3D8, C4D8, C6D8, C7D8, C9D8, C10D8 etc. for all patients consented under the amended protocol, as well as all patients who will be re-consented during the study under the amended protocol.

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Protocol Amendment #1 New Arm B: (Dacarbazine) Schedule

For Arm B: Dacarbazine there will be no Day 8 visits available in EDC except for Cycle 1 Day 8 and Cycle 2 Day 8 Continuation Form (CONT) was moved to Day 1 for all cycles past cycle 2. Dynamics were adjusted so that no CXD8 visits are available for Dacarbazine subjects past cycle 2. C3D1 will have CONT panel, which, when answered ‘Yes’, will trigger C4D1, etc.

Note: This will not happen for patients already with these Forms triggered and completed.

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Please enter the following on the eCRF previous surgical procedures (i.e. resection of STS)

Significant physical examination findings

Allergic conditions (specify substance and reaction)

MHX : Medical History

Please enter the following on the eCRF Blood transfusions.Type of transfusions (i.e. PRBC – packed red

blood cells) should be specified for coding purposes

CM : Blood transfusions

Please enter the following on the eCRF Total number of of target lesions entered in Non-LNL + LNL should

add up to a maximum of 5 lesions

Maximum of 2 per body organ

All other lesions are to be entered in Non-Target lesion eCRF

To start respective eCRF’s at Lesion #1

Target lesions (LNL and Non-LNL)

TL – LNL :Target Lesion – Lymph Node

TL-Non-LNL :Target non-Lymph Nodes

Please enter the following on the eCRF If there are no lymph node target lesions identified at baseline, sum of

diameter LN for subsequent timepoints should be ticked “NA”

If there are no non-lymph node target lesions identified at baseline,

sum of diameter non-LNL for subsequent timepoints should be ticked

“NA”

NE should only be used for the following situations

Poor quality of scan

Lesions identified at Screening were not assessed on subsequent timepoints as

scan was not done.

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TMPT RESP: Tumor Timepoint response

TMPT RESP: Tumor Timepoint response

CheckIf there is no TL – LN (Lymph Node target lesions), sum of diameters of LN is “NA (not applicable, no lymph node target lesions at baseline)If there is LN target lesion and NLN target lesions entered, please check the calculations of the sum of diameters for both LN target lesions and NLN target lesions

EXAMPLE - TMPT RESP – Incorrect!

Patient does not have TL-LNL eCRF. Hence TMPT response should be not be NE

EXAMPLE OF TMPT RESP – Incorrect!


Incorrect

If NE (Not Evaluable) is ticked instead of NA (Not Applicable), the total sum of target lesions diameters will be “NE”

Total sum of target lesion diameters should be 120mm

EXAMPLE OF TMPT RESP – Correct!


No TL-LNL page for the patient. Hence TMP response should be NA

EXAMPLE OF TMPT RESP – Correct!


If NE (Not Evaluable) is ticked instead of NA (Not Applicable), the total sum of target lesions diameters will be “NE”NA (Not Applicable) is correctly ticked here, so the total sum of target lesion diameters is correctly populated : 69mm)

Certain scans NOT done at a Timepoint

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If a lesion is identified as target or non-target lesion at baseline, and these cannot be assessed at a protocol required timepoint due to the following The quality of the scan

Scans were not done for any reason

Not Evaluable (NE) should be ticked for the lesion. It should not be left blank

Aforementioned is also true when an unscheduled scan of a body/organ is done at an unscheduled timepoint

Unscheduled timepoint/scans

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To be entered in the SCAN eCRF Timepoint number should be determined and then entered

under “Other, week “__” All lesions(TL-LNL, TL-Non-LNL, NONTL) identified at

screening will need to be assessed at the Unscheduled timepoint

TMPT response will also need to be completed for the Unscheduled timepoint.

Unscheduled timepoint/scans


Use the Other week to enter Unscheduled timepoint at all Tumor pages.

TUMOR UNL eCRF

MUST complete UNL eCRF ONLY once for the last

time point at which patient was radiologically assessed

To complete this eCRF even if there were no New lesions to confirm this information was assessed atleast once

If only Screening visit was assessed and patient was discontinued then DO NOT complete this eCRF

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Questions!! Thank You!!


CONFIDENTIAL CRA Training Agenda 1 TopicTimePresenter 1 Protocol Amendment 01 & 02...

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