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"annotation_type": "footnote", "annotation_text": "Visits continue every 4 weeks until study treatment discontinuation.", "marker_locations": [ { "table_number": 1, "location_type": "schedule_cell", "row_position": 1, "column_position": 8 } ] }, { "annotation_marker": "3", "annotation_type": "footnote", "annotation_text": "C1/D1 is day of first dose.", "marker_locations": [ { "table_number": 1, "location_type": "schedule_cell", "row_position": 2, "column_position": 3 } ] }, { "annotation_marker": "4", "annotation_type": "footnote", "annotation_text": "A separate ICF may be signed prior to the screening period for Myriad Integrated BRACAnalysis® testing in order to facilitate early testing. Depending on local site requirements, patients may sign a single study ICF prior to the screening period to facilitate early gBRCAmut testing only. All other study tests and procedures must be done in the screening window (Day -28 to Day -1).", "marker_locations": [ { "table_number": 1, "location_type": "activity_name", "row_position": 3 } ] }, { "annotation_marker": "5", "annotation_type": "footnote", "annotation_text": "Local gBRCAmut results that had been performed previously should be entered into eCRF at screening.", "marker_locations": [ { "table_number": 1, "location_type": "activity_name", "row_position": 6 } ] }, { "annotation_marker": "6", "annotation_type": "footnote", "annotation_text": "Centralized gBRCAmut testing of DNA by Integrated BRACAnalysis® at Myriad must be completed prior to randomization. The sample may be submitted prior to the screening period for patients who are identified for a Screening Visit to occur. DNA from this sample will be stored and may be used at a later time for biomarker testing including potential to bridging to candidate companion diagnostic assays.", "marker_locations": [ { "table_number": 1, "location_type": "schedule_cell", "row_position": 7, "column_position": 2 } ] }, { "annotation_marker": "7", "annotation_type": "footnote", "annotation_text": "Negative serum pregnancy test required within 72 hours from first dose of study treatment for females of childbearing potential; repeated every 3 months for duration of study (ie, Cycle 4, Cycle 7, etc).", "marker_locations": [ { "table_number": 1, "location_type": "schedule_cell", "row_position": 9, "column_position": 2 }, { "table_number": 1, "location_type": "schedule_cell", "row_position": 9, "column_position": 8 } ] }, { "annotation_marker": "8", "annotation_type": "footnote", "annotation_text": "Randomization must occur within 72 hours prior to first dose.", "marker_locations": [ { "table_number": 1, "location_type": "schedule_cell", "row_position": 10, "column_position": 2 } ] }, { "annotation_marker": "9", "annotation_type": "footnote", "annotation_text": "Height obtained at screening only.", "marker_locations": [ { "table_number": 1, "location_type": "activity_name", "row_position": 12 } ] }, { "annotation_marker": "10", "annotation_type": "footnote", "annotation_text": "SAEs recorded up to 30 days after study treatment discontinuation.", "marker_locations": [ { "table_number": 1, "location_type": "schedule_cell", "row_position": 14, "column_position": 9 } ] }, { "annotation_marker": "11", "annotation_type": "footnote", "annotation_text": "If Screening laboratory testing (serum chemistry, CBC, coagulation) performed within 72 hours of Day 1, repeat testing not required.", "marker_locations": [ { "table_number": 1, "location_type": "schedule_cell", "row_position": 16, "column_position": 3 } ] }, { "annotation_marker": "12", "annotation_type": "footnote", "annotation_text": "If dose interruption or modification is required at any point on study because of hematologic toxicity, weekly blood draws for CBC will be monitored until the adverse event resolves, and to ensure safety of the new dose, weekly blood draws for CBC will be also be required for an additional 4 weeks after the adverse event has been resolved to the specified levels, after which monitoring every 4 weeks may resume.", "marker_locations": [ { "table_number": 1, "location_type": "activity_name", "row_position": 17 } ] }, { "annotation_marker": "13", "annotation_type": "footnote", "annotation_text": "CA-125 levels must be normal at screening or > 90% decrease as compared with baseline prior to last platinum-based chemotherapy course. Abnormal CA-125 levels during study do not represent disease progression; however, they may prompt imaging if clinically indicated. CA-125 sample within 72 hours of dose on Cycle 1/Day 1.", "marker_locations": [ { "table_number": 1, "location_type": "activity_name", "row_position": 18 } ] }, { "annotation_marker": "14", "annotation_type": "footnote", "annotation_text": "For determination of CA-125 progression, at least 2 CA-125 values at least 1 week apart are required for confirmation (Section 6.1).", "marker_locations": [ { "table_number": 1, "location_type": "activity_name", "row_position": 18 } ] }, { "annotation_marker": "15", "annotation_type": "footnote", "annotation_text": "Urinalysis parameters must include: specific gravity, leukocyte esterase, nitrite, blood, protein, glucose, ketones, urobilinogen, and bilirubin.", "marker_locations": [ { "table_number": 1, "location_type": "activity_name", "row_position": 19 } ] }, { "annotation_marker": "16", "annotation_type": "footnote", "annotation_text": "Patients will have a 12-lead ECG at Screening, Baseline (predose, within 30 minutes), 2 hours postdose on Day 1(within 30 minutes), Cycle 2/Day 1, (predose, 2 hours postdose, within 30 minutes) and upon study treatment discontinuation. Note that the ECG is to be completed prior to the PK blood draw.", "marker_locations": [ { "table_number": 1, "location_type": "activity_name", "row_position": 20 } ] }, { "annotation_marker": "17", "annotation_type": "footnote", "annotation_text": "At selected sites, a subset of patients (approximately 24) will undergo triplicate ECG testing on Day 1 only at baseline (predose) and 1, 1.5, 2, 3, 4, 6 and 8 hours postdose. Triplicate ECGs should be performed between 2-5 minutes apart and should be performed prior to blood draws for PK.", "marker_locations": [ { "table_number": 1, "location_type": "schedule_cell", "row_position": 21, "column_position": 3 } ] }, { "annotation_marker": "18", "annotation_type": "footnote", "annotation_text": "Formalin fixed, paraffin-embedded tumor sample (primary or metastatic site) consisting of 100 micron thickness of sections (≥ 80 micron minimum) or unsectioned paraffin block.", "marker_locations": [ { "table_number": 1, "location_type": "activity_name", "row_position": 22 } ] }, { "annotation_marker": "19", "annotation_type": "footnote", "annotation_text": "Blood samples for PK collected on Cycle 1/Day 1 and Cycle 2/Day 1 collected predose (within 30 minutes) and 2 hours postdose (within 30± 15 minutes Note: The exact time of the PK blood draw will be recorded and ECG monitoring is to be completed prior to the PK blood draw.", "marker_locations": [ { "table_number": 1, "location_type": "schedule_cell", "row_position": 23, "column_position": 3 } ] }, { "annotation_marker": "20", "annotation_type": "footnote", "annotation_text": "At selected sites, a subset of patients (approximately 12) undergoing intensive PK on Day1 will have samples collected at baseline (within 30 minutes predose) and 1, 1.5, 2, 3, 4, 6 and 8 hours (± 2 minutes at all time points) postdose. Note: The exact time of the PK blood draw will be recorded and the ECG monitoring is to be completed prior to the PK blood draw.", "marker_locations": [ { "table_number": 1, "location_type": "schedule_cell", "row_position": 23, "column_position": 3 } ] }, { "annotation_marker": "21", "annotation_type": "footnote", "annotation_text": "Additional blood samples for PK on Cycle 4/Day 1 and Cycle 8/Day 1 will be collected at predose (trough) within 30 minutes only.", "marker_locations": [ { "table_number": 1, "location_type": "schedule_cell", "row_position": 23, "column_position": 8 } ] }, { "annotation_marker": "22", "annotation_type": "footnote", "annotation_text": "RECIST tumor assessment via CT or MRI scan of abdomen/pelvis and clinically indicated areas required at baseline, then after every 2 cycles (ie, 8 weeks with a window of ± 7 days from date of visit) through Cycle 14 (56 weeks), then after every 6 cycles (24 weeks with a window of ± 7 days) until study treatment discontinuation; at this point, a final follow-up set of imaging is required. PET/CT may be used according to RECIST guidelines. Cycle timing will not be delayed for treatment interruptions, and tumor assessment should occur according to this schedule regardless of whether study treatment is interrupted. If a patient discontinues treatment for clinical progression and does not meet the criteria specified in the protocol, scans and CA-125 testing should continue at the specified intervals until progression is confirmed or until the start of subsequent anticancer treatment.", "marker_locations": [ { "table_number": 1, "location_type": "activity_name", "row_position": 24 } ] }, { "annotation_marker": "23", "annotation_type": "footnote", "annotation_text": "Chest CT/MRI if not done as part of RECIST tumor assessment at Screening. If the chest CT/MRI is clear at screening, repeat chest imaging is not required in the absence of lesions to be followed or in the absence of clinical indication requiring follow‐up.", "marker_locations": [ { "table_number": 1, "location_type": "activity_name", "row_position": 25 } ] }, { "annotation_marker": "24", "annotation_type": "footnote", "annotation_text": "PROs (FOSI, EQ-5D-5L, neuropathy questionnaire) will be collected while on study treatment every 8 weeks through the first year, then every 12 weeks thereafter. If the patient discontinues study treatment, assessment will occur at that time and then 8 weeks (± 2 weeks) later, regardless of status of subsequent treatment. PROs should be administered before conducting any other procedures.", "marker_locations": [ { "table_number": 1, "location_type": "activity_name", "row_position": 26 } ] }, { "annotation_marker": "25", "annotation_type": "footnote", "annotation_text": "No new capsules dispensed", "marker_locations": [ { "table_number": 1, "location_type": "schedule_cell", "row_position": 27, "column_position": 9 } ] }, { "annotation_marker": "26", "annotation_type": "footnote", "annotation_text": "Every 90 days following study treatment discontinuation.", "marker_locations": [ { "table_number": 1, "location_type": "schedule_cell", "row_position": 28, "column_position": 10 } ] }, { "annotation_marker": "27", "annotation_type": "footnote", "annotation_text": "In addition to survival, this assessment includes outcomes for subsequent anticancer therapies including any new malignancy information.", "marker_locations": [ { "table_number": 1, "location_type": "activity_name", "row_position": 29 } ] }, { "annotation_marker": "28", "annotation_type": "footnote", "annotation_text": "For any suspected MDS/AML case reported while a patient is receiving treatment or being followed for post-treatment assessments, bone marrow aspirate and biopsy testing must be completed by a local hematologist. Testing completed as part of standard of care is sufficient as long as the methods are acceptable to the Sponsor’s Medical Monitor. The study site must receive a copy of the hematologist's report of aspirate/biopsy findings (which must include a classification according to WHO criteria²⁰) and other sample testing results related to MDS/AML.", "marker_locations": [ { "table_number": 1, "location_type": "schedule_cell", "row_position": 30, "column_position": 3 }, { "table_number": 1, "location_type": "schedule_cell", "row_position": 30, "column_position": 4 }, { "table_number": 1, "location_type": "schedule_cell", "row_position": 30, "column_position": 5 }, { "table_number": 1, "location_type": "schedule_cell", "row_position": 30, "column_position": 6 }, { "table_number": 1, "location_type": "schedule_cell", "row_position": 30, "column_position": 7 }, { "table_number": 1, "location_type": "schedule_cell", "row_position": 30, "column_position": 8 }, { "table_number": 1, "location_type": "schedule_cell", "row_position": 30, "column_position": 9 }, { "table_number": 1, "location_type": "schedule_cell", "row_position": 30, "column_position": 10 } ] } ], "review_items": [ { "id": "D1", "severity": "medium", "location": { "page": 63, "row_position": 1 }, "call_made": "The top header row labelled 'Cycle' is typed as a cycle row (printed Table 7, row 1; the same call is made for printed Table 9, row 1, also labelled 'Cycle').", "alternative": "Type these rows as epoch rows, because they also carry study phases (Screening, Study Treatment Discontinuation, Post Treatment Assessments) rather than only numbered cycles.", "report_section": "2.3" }, { "id": "D2", "severity": "medium", "location": { "page": 66, "row_position": 30 }, "call_made": "'Bone marrow aspirate and biopsy' is a top-level activity (indentation 0) like every other row; its one leading space in the source cell is treated as a typing artefact.", "alternative": "Treat the leading space as indentation, making the row a child (level 1) of the row above it ('Survival assessment').", "report_section": "2.3" } ] }