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NCT02576431

A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors

Version 16 to 17 · Bayer

Patch inspector

Version 16 to 17

56 operations 7 path groups ctgov_internal_history
ClinicalTrials.gov
Severity is deterministic uncalibrated triage metadata, not validated review priority. Operation-level severity is inferred from deterministic path rules. Rule matches shown per operation are approximate previews (they skip the pipeline's suppression passes); the authoritative classification is the stored event record.
Plain-language summary

Manual review pending.

Rules fired
contact_admin_changeeligibility_criteria_changeprimary_outcome_any_changesecondary_outcome_any_change
Value signals
[
  {
    "path": "/protocolSection/statusModule/completionDateStruct/date",
    "signal": "timeline_significant_shift",
    "category": "timeline_significant_shift",
    "new_type": "ESTIMATED",
    "old_type": "ESTIMATED",
    "severity": "medium",
    "direction": "later",
    "new_value": "2019-12",
    "old_value": "2019-04",
    "delta_days": 244,
    "date_struct": "completionDateStruct",
    "new_precision": "month",
    "old_precision": "month"
  }
]
Provenance
Source
ctgov_internal_history
Fetched
2026-06-18 19:12:17+00
Raw hash
cec05122d9a7c1edfc1ee5a9d2ad001bea8f806532d743e5f6cf64f0b544518e
Payload
Source URL
Primary outcomes Outcome measures that define the trial's primary evidence target. Triage: Critical 1 ops
replace /protocolSection/outcomesModule/primaryOutcomes/0/measure
Triage: Critical
Primary Outcome Change Operation 37
Matched rules
  • primary_outcome_any_change Any add/remove/replace under primary outcome measures is critical review priority.
Before
Best Overall Response of confirmed CR or PR as measured by RECIST 1.1 or RANO criteria as appropriate to tumor type
After
Overall Response Rate of confirmed CR or PR as determined by an Independent Radiology Committee using RECIST 1.1 or RANO criteria
Eligibility Criteria and population definition changes. Triage: High 3 ops
replace /protocolSection/eligibilityModule/eligibilityCriteria
Triage: High
Eligibility Change Operation 50
Matched rules
  • eligibility_criteria_change Eligibility criteria changes can alter the studied population.
Before
<p>Key Inclusion Criteria:</p><ol><li>Locally-advanced or metastatic malignancy with an NTRK1, NTRK2 or NTRK3 gene fusion, identified through molecular assays as routinely performed at CLIA or other similarly-certified laboratories.</li><li>Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy.</li><li><p>Subjects must have at least one measurable lesion as defined by RECIST 1.1 (Eisenhauer 2009).
Subjects without RECIST measurable disease (e.g., evaluable disease only) will be eligible for enrollment to Cohort 8, regardless of tumor type.
Subjects in Cohort 7 (primary CNS tumors) should meet the following criteria:</p><ul><li>Have received prior treatment including radiation and&#x2F;or chemotherapy, with radiation completed &gt; 12 weeks prior to C1D1 of therapy.</li><li>Have ≥ 1 site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging [MRI] and evaluable by RANO criteria), with the size of at least one of the measurable lesions ≥ 1 cm in each dimension and noted on more than one imaging slice.</li><li>Imaging study performed within 28 days before enrollment while on stable dose steroid medication for at least 5 days immediately before and during the imaging study.</li></ul></li><li><p>Adequate organ function as defined by the following criteria:</p><ul><li>Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) &lt; 2.5 upper limit of normal (ULN), or AST and ALT &lt; 5 ULN if liver function abnormalities are due to underlying malignancy.</li><li>Total bilirubin &lt; 2.0 ULN.
Subjects with a known history of Gilberts Disease and an isolated elevation of indirect bilirubin are eligible.</li><li>Serum creatinine &lt; 2.0 ULN OR an estimated glomerular filtration rate ≥ 30 mL&#x2F;minute using the Cockroft-Gault formula.</li></ul></li><li>Ability to swallow capsules,</li></ol><p>Key Exclusion Criteria:</p><ol><li>Symptomatic or unstable brain metastases.
(Note: Subjects with asymptomatic brain metastases are eligible to participate in the study).
Subjects with primary CNS tumors are eligible.</li><li>Pregnancy or lactation.</li></ol>
After
<p>Key Inclusion Criteria:</p><ol><li>Locally-advanced or metastatic malignancy with an NTRK1, NTRK2 or NTRK3 gene fusion, identified through molecular assays as routinely performed at CLIA or other similarly-certified laboratories.</li><li>Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy.</li><li><p>Adequate organ function as defined by the following criteria:</p><ul><li>Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) &lt; 2.5 upper limit of normal (ULN), or AST and ALT &lt; 5 ULN if liver function abnormalities are due to underlying malignancy.</li><li>Total bilirubin &lt; 2.5 ULN.
Subjects with a known history of Gilberts Disease and an isolated elevation of indirect bilirubin are eligible.</li><li>Serum creatinine &lt; 2.0 ULN OR an estimated glomerular filtration rate ≥ 30 mL&#x2F;minute using the Cockroft-Gault formula.</li></ul></li></ol><p>Key Exclusion Criteria:</p><p>1. Pregnancy or lactation.</p>
replace /protocolSection/eligibilityModule/minimumAge
Triage: Uncategorized
Uncategorized Operation 51
Before
18 Years
After
12 Years
add /protocolSection/eligibilityModule/stdAges/0
Triage: Uncategorized
Uncategorized Operation 52
After
CHILD
Secondary outcomes Additional endpoints and outcome descriptions. Triage: High 12 ops
replace /protocolSection/outcomesModule/secondaryOutcomes/0/measure
Triage: High
Secondary Outcome Change Operation 38
Matched rules
  • secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.
Before
Duration of Response (DOR)
After
Overall Response Rate of confirmed CR or PR as determined by the treating investigator using RECIST 1.1 or RANO criteria
replace /protocolSection/outcomesModule/secondaryOutcomes/1/measure
Triage: High
Secondary Outcome Change Operation 39
Matched rules
  • secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.
Before
Progression Free Survival (PFS)
After
Duration of response for subjects with best overall response of confirmed CR or PR by Independent Radiology Committee
add /protocolSection/outcomesModule/secondaryOutcomes/2
Triage: High
Secondary Outcome Change Operation 40
Matched rules
  • secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.
After
{
  "measure": "Duration of response for subjects with best overall response of confirmed CR or PR by the treating investigator",
  "timeFrame": "Up to 30 months"
}
add /protocolSection/outcomesModule/secondaryOutcomes/3
Triage: High
Secondary Outcome Change Operation 41
Matched rules
  • secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.
After
{
  "measure": "Progression Free Survival",
  "timeFrame": "Up to 30 months",
  "description": "Number of moths from initiation of Loxo-101 to the earlier of diease progression or death due to any cause"
}
replace /protocolSection/outcomesModule/secondaryOutcomes/5/measure
Triage: High
Secondary Outcome Change Operation 42
Matched rules
  • secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.
Before
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
After
Comparison of Progression Free Survival following initiation of Loxo-101 to that following the line of therapy immediately preceding Loxo-101
replace /protocolSection/outcomesModule/secondaryOutcomes/5/description
Triage: High
Secondary Outcome Change Operation 43
Matched rules
  • secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.
Before
To assess the safety profile and tolerability of LOXO-101
After
In each subject who has received prior therapy
replace /protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame
Triage: High
Secondary Outcome Change Operation 44
Matched rules
  • secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.
Before
Up to 30 months
After
UP to 30 months
add /protocolSection/outcomesModule/secondaryOutcomes/6
Triage: High
Secondary Outcome Change Operation 45
Matched rules
  • secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.
After
{
  "measure": "Incidence of Adverse Events",
  "timeFrame": "Up to 30 months"
}
add /protocolSection/outcomesModule/secondaryOutcomes/7
Triage: High
Secondary Outcome Change Operation 46
Matched rules
  • secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.
After
{
  "measure": "Severity of Adverse Events",
  "timeFrame": "Up to 30 months"
}
add /protocolSection/outcomesModule/secondaryOutcomes/8
Triage: High
Secondary Outcome Change Operation 47
Matched rules
  • secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.
After
{
  "measure": "Duration of Adverse Events",
  "timeFrame": "Up to 30 months"
}
add /protocolSection/outcomesModule/secondaryOutcomes/9
Triage: High
Secondary Outcome Change Operation 48
Matched rules
  • secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.
After
{
  "measure": "Changes from baseline in clinical safety laboratory values",
  "timeFrame": "Up to 30 months"
}
add /protocolSection/outcomesModule/secondaryOutcomes/10
Triage: High
Secondary Outcome Change Operation 49
Matched rules
  • secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.
After
{
  "measure": "Changes from baseline in vital signs",
  "timeFrame": "Up to 30 months"
}
Timeline Start, primary completion, and completion date movement. Triage: Medium 1 ops
replace /protocolSection/statusModule/completionDateStruct/date
Triage: Medium
Timeline Shift Operation 6
Matched rules
  • completion_timeline_change Completion date changes are operational timeline signals.
Before
2019-04
After
2019-12
Contacts and locations Site, contact, and location updates that are usually operational. Triage: Low 3 ops
replace /protocolSection/contactsLocationsModule/centralContacts/0/name
Triage: Low
Administrative Contact Change Operation 53
Matched rules
  • contact_admin_change Central contact updates are usually administrative.
Before
Maegan Deegan
After
Patient Advocacy
replace /protocolSection/contactsLocationsModule/centralContacts/0/email
Triage: Low
Administrative Contact Change Operation 54
Matched rules
  • contact_admin_change Central contact updates are usually administrative.
Before
maegan@loxooncology.com
After
clinicaltrials@loxooncology.com
remove /protocolSection/contactsLocationsModule/centralContacts/1
Triage: Low
Administrative Contact Change Operation 55
Matched rules
  • contact_admin_change Central contact updates are usually administrative.
Before
{
  "name": "Lia Donahue",
  "role": "CONTACT",
  "email": "lia@loxooncology.com",
  "phone": "1-855-NTRK-123"
}
Other registry fields Changes outside the current high-signal rule families. Triage: Uncategorized 34 ops
replace /protocolSection/statusModule/statusVerifiedDate
Triage: Uncategorized
Uncategorized Operation 3
Before
2017-03
After
2017-05
replace /protocolSection/statusModule/expandedAccessInfo/hasExpandedAccess
Triage: Uncategorized
Uncategorized Operation 4
Before
false
After
true
add /protocolSection/statusModule/expandedAccessInfo/nctId
Triage: Uncategorized
Uncategorized Operation 5
After
NCT03025360
replace /protocolSection/statusModule/lastUpdateSubmitDate
Triage: Uncategorized
Uncategorized Operation 7
Before
2017-03-23
After
2017-05-26
replace /protocolSection/statusModule/lastUpdatePostDateStruct/date
Triage: Uncategorized
Uncategorized Operation 8
Before
2017-03-27
After
2017-05-31
replace /protocolSection/descriptionModule/detailedDescription
Triage: Uncategorized
Uncategorized Operation 9
Before
<p>This is a Phase II, multi-center, open-label study of patients with advanced solid tumors harboring a fusion of NTRK1, NTRK2 or NTRK3.
Patients with NTRK1, NTRK2 or NTRK3 fusion-positive cancers will be identified through molecular assay.</p><p>LOXO-101 will be administered at 100mg twice daily (BID), with each cycle consisting of 28 days of dosing administered on a continuous basis.</p><p>The study will include 8 cohorts of patients with tumors bearing NTRK fusions, including non small cell lung cancer, thyroid cancer, sarcoma, colorectal cancer, salivary gland cancer, biliary cancer and primary CNS tumor, as well as a cohort that will enroll patients not included in the histologies listed above.</p>
After
<p>This is a Phase II, multi-center, open-label study of patients with advanced solid tumors harboring a fusion of NTRK1, NTRK2 or NTRK3.
Patients with NTRK1, NTRK2 or NTRK3 fusion-positive cancers will be identified through molecular assay.</p><p>LOXO-101 will be administered orally at 100mg twice daily (BID), with each cycle consisting of 28 days of dosing administered on a continuous basis.</p><p>The study will analyze 8 cohorts of patients with tumors bearing NTRK fusions, including non small cell lung cancer, thyroid cancer, sarcoma, colorectal cancer, salivary gland cancer, biliary cancer and primary CNS tumor, as well as a cohort that will enroll patients not included in the histologies listed above.</p>
add /protocolSection/conditionsModule/conditions/15
Triage: Uncategorized
Uncategorized Operation 10
After
Pancreatic Neoplasms
add /protocolSection/conditionsModule/conditions/16
Triage: Uncategorized
Uncategorized Operation 11
After
Ovarian Neoplasms
add /protocolSection/conditionsModule/conditions/17
Triage: Uncategorized
Uncategorized Operation 12
After
Carcinoma, Renal Cell
add /protocolSection/conditionsModule/conditions/18
Triage: Uncategorized
Uncategorized Operation 13
After
Cholangiocarcinoma
add /protocolSection/conditionsModule/conditions/19
Triage: Uncategorized
Uncategorized Operation 14
After
Carcinoma
add /protocolSection/conditionsModule/conditions/20
Triage: Uncategorized
Uncategorized Operation 15
After
Carcinoma, Bronchogenic
add /protocolSection/conditionsModule/conditions/21
Triage: Uncategorized
Uncategorized Operation 16
After
Bronchial Neoplasms
add /protocolSection/conditionsModule/conditions/22
Triage: Uncategorized
Uncategorized Operation 17
After
Lung Neoplasms
add /protocolSection/conditionsModule/conditions/23
Triage: Uncategorized
Uncategorized Operation 18
After
Respiratory Tract Neoplasms
add /protocolSection/conditionsModule/conditions/24
Triage: Uncategorized
Uncategorized Operation 19
After
Thoracic Neoplasms
add /protocolSection/conditionsModule/conditions/25
Triage: Uncategorized
Uncategorized Operation 20
After
Neoplasms, Nerve Tissue
add /protocolSection/conditionsModule/conditions/26
Triage: Uncategorized
Uncategorized Operation 21
After
Nevi and Melanomas
add /protocolSection/conditionsModule/keywords/13
Triage: Uncategorized
Uncategorized Operation 22
After
larotrectinib
add /protocolSection/conditionsModule/keywords/14
Triage: Uncategorized
Uncategorized Operation 23
After
fusion
add /protocolSection/conditionsModule/keywords/15
Triage: Uncategorized
Uncategorized Operation 24
After
tumors
add /protocolSection/conditionsModule/keywords/16
Triage: Uncategorized
Uncategorized Operation 25
After
CNS tumors
add /protocolSection/conditionsModule/keywords/17
Triage: Uncategorized
Uncategorized Operation 26
After
solid tumors
add /protocolSection/conditionsModule/keywords/18
Triage: Uncategorized
Uncategorized Operation 27
After
central nervous system tumors
add /protocolSection/conditionsModule/keywords/19
Triage: Uncategorized
Uncategorized Operation 28
After
solid CNS tumors
add /protocolSection/conditionsModule/keywords/20
Triage: Uncategorized
Uncategorized Operation 29
After
primary CNS tumor
add /protocolSection/conditionsModule/keywords/21
Triage: Uncategorized
Uncategorized Operation 30
After
Advanced CNS tumor
add /protocolSection/conditionsModule/keywords/22
Triage: Uncategorized
Uncategorized Operation 31
After
Metastatic CNS tumor
add /protocolSection/conditionsModule/keywords/23
Triage: Uncategorized
Uncategorized Operation 32
After
NTRK1 fusion
add /protocolSection/conditionsModule/keywords/24
Triage: Uncategorized
Uncategorized Operation 33
After
NTRK2 fusion
add /protocolSection/conditionsModule/keywords/25
Triage: Uncategorized
Uncategorized Operation 34
After
NTRK3 fusion
add /protocolSection/conditionsModule/keywords/26
Triage: Uncategorized
Uncategorized Operation 35
After
ETV6-NTRK3
add /protocolSection/conditionsModule/keywords/27
Triage: Uncategorized
Uncategorized Operation 36
After
ETV6 fusion
add /protocolSection/ipdSharingStatementModule
Triage: Uncategorized
Uncategorized Operation 56
After
{
  "ipdSharing": "NO"
}
Sponsor and administrative fields Sponsor, collaborator, oversight, or registry maintenance changes. Triage: Uncategorized 2 ops
replace /protocolSection/identificationModule/briefTitle
Triage: Uncategorized
Uncategorized Operation 1
Before
Study of LOXO-101 in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE)
After
Study of LOXO-101 (Larotrectinib) in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE)
replace /protocolSection/identificationModule/officialTitle
Triage: Uncategorized
Uncategorized Operation 2
Before
A Phase II Basket Study of the Oral TRK Inhibitor LOXO-101 in Subjects With NTRK Fusion-Positive Tumors
After
A Phase II Basket Study of the Oral TRK Inhibitor LOXO-101 (Larotrectinib) in Subjects With NTRK Fusion-Positive Tumors
Raw JSON Patch
[
  {
    "op": "replace",
    "path": "/protocolSection/identificationModule/briefTitle",
    "value": "Study of LOXO-101 (Larotrectinib) in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE)"
  },
  {
    "op": "replace",
    "path": "/protocolSection/identificationModule/officialTitle",
    "value": "A Phase II Basket Study of the Oral TRK Inhibitor LOXO-101 (Larotrectinib) in Subjects With NTRK Fusion-Positive Tumors"
  },
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/statusVerifiedDate",
    "value": "2017-05"
  },
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/expandedAccessInfo/hasExpandedAccess",
    "value": true
  },
  {
    "op": "add",
    "path": "/protocolSection/statusModule/expandedAccessInfo/nctId",
    "value": "NCT03025360"
  },
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/completionDateStruct/date",
    "value": "2019-12"
  },
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/lastUpdateSubmitDate",
    "value": "2017-05-26"
  },
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
    "value": "2017-05-31"
  },
  {
    "op": "replace",
    "path": "/protocolSection/descriptionModule/detailedDescription",
    "value": "<p>This is a Phase II, multi-center, open-label study of patients with advanced solid tumors harboring a fusion of NTRK1, NTRK2 or NTRK3.\nPatients with NTRK1, NTRK2 or NTRK3 fusion-positive cancers will be identified through molecular assay.</p><p>LOXO-101 will be administered orally at 100mg twice daily (BID), with each cycle consisting of 28 days of dosing administered on a continuous basis.</p><p>The study will analyze 8 cohorts of patients with tumors bearing NTRK fusions, including non small cell lung cancer, thyroid cancer, sarcoma, colorectal cancer, salivary gland cancer, biliary cancer and primary CNS tumor, as well as a cohort that will enroll patients not included in the histologies listed above.</p>"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/conditions/15",
    "value": "Pancreatic Neoplasms"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/conditions/16",
    "value": "Ovarian Neoplasms"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/conditions/17",
    "value": "Carcinoma, Renal Cell"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/conditions/18",
    "value": "Cholangiocarcinoma"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/conditions/19",
    "value": "Carcinoma"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/conditions/20",
    "value": "Carcinoma, Bronchogenic"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/conditions/21",
    "value": "Bronchial Neoplasms"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/conditions/22",
    "value": "Lung Neoplasms"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/conditions/23",
    "value": "Respiratory Tract Neoplasms"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/conditions/24",
    "value": "Thoracic Neoplasms"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/conditions/25",
    "value": "Neoplasms, Nerve Tissue"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/conditions/26",
    "value": "Nevi and Melanomas"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/13",
    "value": "larotrectinib"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/14",
    "value": "fusion"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/15",
    "value": "tumors"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/16",
    "value": "CNS tumors"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/17",
    "value": "solid tumors"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/18",
    "value": "central nervous system tumors"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/19",
    "value": "solid CNS tumors"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/20",
    "value": "primary CNS tumor"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/21",
    "value": "Advanced CNS tumor"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/22",
    "value": "Metastatic CNS tumor"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/23",
    "value": "NTRK1 fusion"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/24",
    "value": "NTRK2 fusion"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/25",
    "value": "NTRK3 fusion"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/26",
    "value": "ETV6-NTRK3"
  },
  {
    "op": "add",
    "path": "/protocolSection/conditionsModule/keywords/27",
    "value": "ETV6 fusion"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
    "value": "Overall Response Rate of confirmed CR or PR as determined by an Independent Radiology Committee using RECIST 1.1 or RANO criteria"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/0/measure",
    "value": "Overall Response Rate of confirmed CR or PR as determined by the treating investigator using RECIST 1.1 or RANO criteria"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/measure",
    "value": "Duration of response for subjects with best overall response of confirmed CR or PR by Independent Radiology Committee"
  },
  {
    "op": "add",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/2",
    "value": {
      "measure": "Duration of response for subjects with best overall response of confirmed CR or PR by the treating investigator",
      "timeFrame": "Up to 30 months"
    }
  },
  {
    "op": "add",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/3",
    "value": {
      "measure": "Progression Free Survival",
      "timeFrame": "Up to 30 months",
      "description": "Number of moths from initiation of Loxo-101 to the earlier of diease progression or death due to any cause"
    }
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/5/measure",
    "value": "Comparison of Progression Free Survival following initiation of Loxo-101 to that following the line of therapy immediately preceding Loxo-101"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/5/description",
    "value": "In each subject who has received prior therapy"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame",
    "value": "UP to 30 months"
  },
  {
    "op": "add",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/6",
    "value": {
      "measure": "Incidence of Adverse Events",
      "timeFrame": "Up to 30 months"
    }
  },
  {
    "op": "add",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/7",
    "value": {
      "measure": "Severity of Adverse Events",
      "timeFrame": "Up to 30 months"
    }
  },
  {
    "op": "add",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/8",
    "value": {
      "measure": "Duration of Adverse Events",
      "timeFrame": "Up to 30 months"
    }
  },
  {
    "op": "add",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/9",
    "value": {
      "measure": "Changes from baseline in clinical safety laboratory values",
      "timeFrame": "Up to 30 months"
    }
  },
  {
    "op": "add",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/10",
    "value": {
      "measure": "Changes from baseline in vital signs",
      "timeFrame": "Up to 30 months"
    }
  },
  {
    "op": "replace",
    "path": "/protocolSection/eligibilityModule/eligibilityCriteria",
    "value": "<p>Key Inclusion Criteria:</p><ol><li>Locally-advanced or metastatic malignancy with an NTRK1, NTRK2 or NTRK3 gene fusion, identified through molecular assays as routinely performed at CLIA or other similarly-certified laboratories.</li><li>Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy.</li><li><p>Adequate organ function as defined by the following criteria:</p><ul><li>Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) &lt; 2.5 upper limit of normal (ULN), or AST and ALT &lt; 5 ULN if liver function abnormalities are due to underlying malignancy.</li><li>Total bilirubin &lt; 2.5 ULN.\nSubjects with a known history of Gilberts Disease and an isolated elevation of indirect bilirubin are eligible.</li><li>Serum creatinine &lt; 2.0 ULN OR an estimated glomerular filtration rate ≥ 30 mL&#x2F;minute using the Cockroft-Gault formula.</li></ul></li></ol><p>Key Exclusion Criteria:</p><p>1. Pregnancy or lactation.</p>"
  },
  {
    "op": "replace",
    "path": "/protocolSection/eligibilityModule/minimumAge",
    "value": "12 Years"
  },
  {
    "op": "add",
    "path": "/protocolSection/eligibilityModule/stdAges/0",
    "value": "CHILD"
  },
  {
    "op": "replace",
    "path": "/protocolSection/contactsLocationsModule/centralContacts/0/name",
    "value": "Patient Advocacy"
  },
  {
    "op": "replace",
    "path": "/protocolSection/contactsLocationsModule/centralContacts/0/email",
    "value": "clinicaltrials@loxooncology.com"
  },
  {
    "op": "remove",
    "path": "/protocolSection/contactsLocationsModule/centralContacts/1"
  },
  {
    "op": "add",
    "path": "/protocolSection/ipdSharingStatementModule",
    "value": {
      "ipdSharing": "NO"
    }
  }
]