{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT06474663","title":"A Phase I Study Investigating the Combination of Cladribine, Low Dose Cytarabine and Sorafenib Alternating With Decitabine in Pediatric Relapsed and Refractory Acute Leukemias","sponsor":"M.D. Anderson Cancer Center","phases":["PHASE1"],"status":"WITHDRAWN","indication":null,"disease":"acute erythroblastic leukemia"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of RAF1, PDGFRB, KIT has somatic-mutation evidence in acute erythroblastic leukemia","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: RAF1 in acute erythroblastic leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000132155/EFO_1001257","date":"2026-11-11T19:13:14.858Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for RAF1, PDGFRB, KIT in acute erythroblastic leukemia","rule":"Any germline or somatic human genetic evidence for the target in this cancer, counted apart from animal-model and literature evidence","source":{"label":"Open Targets: RAF1 in acute erythroblastic leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000132155/EFO_1001257","date":"2026-11-11T19:13:14.858Z"},"context":[]},{"id":"pediatric_target","label":"Pediatric target","value":"yes","detail":"PDGFRB, KIT on the FDA list","rule":"Target is on FDA's Pediatric Molecular Target List (relevant targets); membership alone neither requires nor waives a study","source":{"label":"FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01))","url":"https://www.fda.gov/media/191157/download?attachment","date":"2026-11-11T07:05:03Z"},"context":[]},{"id":"haematologic","label":"Haematologic cancer","value":"yes","detail":"Haematologic","rule":"From the indication, or the registry conditions when no indication matches","source":{"label":"ClinicalTrials.gov NCT06474663","url":"https://clinicaltrials.gov/study/NCT06474663","date":"2026-11-11T19:13:14.858Z"},"context":[{"figure":"Likelihood of approval from phase 1: 7.5% haematologic vs 4.6% solid","dataset":"BIO / Informa / QLS 2021","years":"2011–2020","caveat":"Population-level, not a prediction."}]}],"facts":[{"label":"Background therapy","text":"Cladribine, Cytarabine, Decitabine: standard agents, not counted in these flags."},{"label":"RAF1 (via Sorafenib)","text":"Open Targets has no association between RAF1 and acute erythroblastic leukemia.","source":{"label":"Open Targets: RAF1 in acute erythroblastic leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000132155/EFO_1001257","date":"2026-11-11T19:13:14.858Z"}},{"label":"PDGFRB (via Sorafenib)","text":"Evidence types in acute erythroblastic leukemia: animal_model; animal_model listed separately from human genetics. Datasources: impc.","source":{"label":"Open Targets: PDGFRB in acute erythroblastic leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000113721/EFO_1001257","date":"2026-11-11T19:13:14.858Z"}},{"label":"KIT (via Sorafenib)","text":"Evidence types in acute erythroblastic leukemia: literature, animal_model; literature and animal_model listed separately from human genetics. Datasources: impc, europepmc.","source":{"label":"Open Targets: KIT in acute erythroblastic leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000157404/EFO_1001257","date":"2026-11-11T19:13:14.858Z"}}],"pending":[{"what":"Normal-tissue expression in vital organs","source":"Human Protein Atlas (ticket 36)"},{"what":"Pan-essential in cell lines","source":"DepMap (ticket 36)"},{"what":"Approved drug on this target","source":"Drugs@FDA (ticket 30)"}]},{"n":2,"question":"Can the result be trusted?","flags":[{"id":"randomised","label":"Randomised","value":"no","detail":"Non-randomised","rule":"Registry allocation field","source":{"label":"ClinicalTrials.gov NCT06474663","url":"https://clinicaltrials.gov/study/NCT06474663","date":"2026-11-11T19:13:14.858Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"yes","detail":"0 enrolled; each patient moves a rate by 100 ÷ 0 = – points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT06474663","url":"https://clinicaltrials.gov/study/NCT06474663","date":"2026-11-11T19:13:14.858Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Safety and adverse events (AEs)","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT06474663","url":"https://clinicaltrials.gov/study/NCT06474663","date":"2026-11-11T19:13:14.858Z"},"context":[{"figure":"Non-OS primary endpoint: odds ratio 2.79 for a positive phase 3","dataset":"Otsuka 2021, 400 phase 3 oncology trials","years":"to 2020","caveat":"Shown with the next figure: a surrogate is easier to hit, and often a weak guide to survival."},{"figure":"52% of surrogate-to-OS correlations are low","dataset":"Prasad 2015","years":"published to 2014","caveat":"Shown with the figure above."}]},{"id":"results_overdue","label":"Results overdue","value":"yes","detail":"Primary completion 2025-07-31, 15 months ago; no results posted","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT06474663","url":"https://clinicaltrials.gov/study/NCT06474663","date":"2026-11-11T19:13:14.858Z"},"context":[{"figure":"40.9% of applicable trials report results within a year","dataset":"Results-reporting studies summarised in spec §11","years":"all therapy areas","caveat":"All areas, not oncology only."}]}],"facts":[],"pending":[{"what":"Treated and evaluable counts, assessor, confirmed response, follow-up and data cutoff","source":"Readout extraction (ticket 32)"},{"what":"Primary endpoint changed between registry versions","source":"Registry versions in the store (ticket 32)"}]},{"n":3,"question":"What must it beat?","flags":[],"facts":[],"pending":[{"what":"Control-arm result and approved therapies for the same segment, with label links","source":"Drugs@FDA, FDA labels and readouts (tickets 30, 32)"}]},{"n":4,"question":"Too crowded, or too late?","flags":[],"facts":[{"label":"Stopped on this target","text":"202 terminated, withdrawn or suspended trials of drugs against RAF1; 41 of the 200 most recent give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"RAF1: what already stopped","url":"/target/ENSG00000132155#stopped","date":"2026-11-11T19:13:14.890Z"}}],"pending":[{"what":"Programs on the target by phase and months behind the leader","source":"Programs and Drugs@FDA (ticket 33)"}]},{"n":5,"question":"Can it be approved, and stay approved?","flags":[{"id":"single_country","label":"Single-country","value":"not published","detail":"The record lists no sites.","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT06474663","url":"https://clinicaltrials.gov/study/NCT06474663?tab=locations","date":"2026-11-11T19:13:14.858Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-000781-PIP01-09 (sorafenib tosilate, Differentiated thyroid cancer): W: decision granting a waiver in all age groups for all conditions or indications, 4 May 2010","rule":"An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name","source":{"label":"EMA EMEA-000781-PIP01-09","url":"https://www.ema.europa.eu/en/medicines/human/paediatric-investigation-plans/emea-000781-pip01-09","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_orphan","label":"EU orphan designation","value":"yes","detail":"EU/3/13/1200 expired 13 Nov 2013: Treatment of papillary thyroid cancer; EU/3/13/1199 expired 13 Nov 2013: Treatment of follicular thyroid cancer; - negative 23 Sept 2019: Treatment of hepatocellular carcinoma; EU/3/06/364 expired 11 Apr 2006: Treatment of hepatocellular carcinoma; +1 more","rule":"An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-orphan_designations-json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_authorised","label":"Authorised in the EU","value":"yes","detail":"Sorafenib Accord: authorised since 9 Nov 2022; Nexavar: authorised since 19 Jul 2006","rule":"An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-medicines_json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"fda_orphan","label":"FDA orphan designation","value":"not published","detail":"FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the link","rule":"Would be: an FDA orphan designation names the drug","source":{"label":"FDA orphan designations search","url":"https://www.accessdata.fda.gov/scripts/opdlisting/oopd/","date":""},"context":[]},{"id":"fda_ped_approval","label":"FDA pediatric oncology approval","value":"no","detail":"FDA's table lists no pediatric approval of Sorafenib","rule":"FDA's Pediatric Oncology Drug Approvals table names the drug","source":{"label":"FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03)","url":"https://www.fda.gov/about-fda/oncology-center-excellence/pediatric-oncology-drug-approvals","date":"2026-11-11T19:13:14.925Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"59 interventional studies of Sorafenib include patients under 18; 15 are recruiting, not yet recruiting or active","rule":"The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age","source":{"label":"ClinicalTrials.gov search","url":"https://clinicaltrials.gov/search?intr=%22Sorafenib%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T19:13:14.935Z"},"context":[]}],"facts":[{"label":"Caveat","text":"Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where the sites are is a fact about the record, not a judgement of its quality."},{"label":"Rare pediatric disease voucher","text":"FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news.","source":{"label":"FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs","url":"https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/rare-pediatric-disease-designation-and-priority-review-voucher-programs","date":"2026-11-11"}}],"pending":[{"what":"Precedent approvals for target, modality and endpoint; accelerated-approval status","source":"Drugs@FDA and FDA accelerated-approval tables (ticket 30)"}]},{"n":6,"question":"Can the sponsor finish?","flags":[],"facts":[{"label":"Sponsor","text":"M.D. Anderson Cancer Center (academic or other)","source":{"label":"ClinicalTrials.gov NCT06474663","url":"https://clinicaltrials.gov/study/NCT06474663","date":"2026-11-11T19:13:14.858Z"}},{"label":"principal investigator","text":"Branko Cuglievan, MD, M.D. Anderson Cancer Center","source":{"label":"Person page","url":"/person/Branko%20Cuglievan%2C%20MD","date":"2026-11-11T19:13:14.858Z"}}],"pending":[{"what":"Filed cash, quarterly spend and the runway arithmetic","source":"SEC XBRL company facts (ticket 37)"},{"what":"Sponsor's completed vs stopped oncology trials and results-reporting record","source":"Registry, by company (ticket 37)"}]}],"limits":"Public records cannot show: sales forecasts; a probability of success for this asset; full deal terms and net prices; FDA designations and action dates before approval (shown only as company-reported); clinical holds unless the company disclosed them; manufacturing; patents on unapproved drugs; whether preclinical findings have been replicated.","sources":[{"label":"ClinicalTrials.gov NCT06474663","url":"https://clinicaltrials.gov/study/NCT06474663","date":"2026-11-11T19:13:14.858Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T19:13:14.858Z"},{"label":"FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01))","url":"https://www.fda.gov/media/191157/download?attachment","date":"2026-11-11T07:05:03Z"}]},"source":"ClinicalTrials.gov + Open Targets","fetchedAt":"2026-11-11T19:13:14.851Z"}