{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT04199026","title":"Implantable Microdevice for the Delivery of Drugs and Their Effect on Tumors in Patients With Metastatic or Recurrent Sarcoma","sponsor":"M.D. Anderson Cancer Center","phases":["NA"],"status":"RECRUITING","indication":null,"disease":"metastatic neoplasm"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of TOP2A, FKBP1A, IGF1R, CSF1R, KIT, LCK has somatic-mutation evidence in metastatic neoplasm","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: TOP2A in metastatic neoplasm","url":"https://platform.opentargets.org/evidence/ENSG00000131747/MONDO_0024883","date":"2026-11-11T18:00:33.483Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for TOP2A, FKBP1A, IGF1R, CSF1R, KIT, LCK in metastatic neoplasm","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: TOP2A in metastatic neoplasm","url":"https://platform.opentargets.org/evidence/ENSG00000131747/MONDO_0024883","date":"2026-11-11T18:00:33.483Z"},"context":[]},{"id":"pediatric_target","label":"Pediatric target","value":"yes","detail":"IGF1R, CSF1R, 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":"no","detail":"Solid tumour","rule":"From the indication, or the registry conditions when no indication matches","source":{"label":"ClinicalTrials.gov NCT04199026","url":"https://clinicaltrials.gov/study/NCT04199026","date":"2026-11-11T18:00:33.483Z"},"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":"Doxorubicin, Ifosfamide, Irinotecan, Temozolomide, Vincristine: standard agents, not counted in these flags."},{"label":"TOP2A (via Doxorubicin Hydrochloride)","text":"Evidence types in metastatic neoplasm: literature; literature listed separately from human genetics. Datasources: europepmc.","source":{"label":"Open Targets: TOP2A in metastatic neoplasm","url":"https://platform.opentargets.org/evidence/ENSG00000131747/MONDO_0024883","date":"2026-11-11T18:00:33.483Z"}},{"label":"FKBP1A (via Everolimus)","text":"Open Targets has no association between FKBP1A and metastatic neoplasm.","source":{"label":"Open Targets: FKBP1A in metastatic neoplasm","url":"https://platform.opentargets.org/evidence/ENSG00000088832/MONDO_0024883","date":"2026-11-11T18:00:33.483Z"}},{"label":"IGF1R (via Ganitumab)","text":"Evidence types in metastatic neoplasm: literature; literature listed separately from human genetics. Datasources: europepmc.","source":{"label":"Open Targets: IGF1R in metastatic neoplasm","url":"https://platform.opentargets.org/evidence/ENSG00000140443/MONDO_0024883","date":"2026-11-11T18:00:33.483Z"}},{"label":"CSF1R (via Pazopanib)","text":"Evidence types in metastatic neoplasm: literature; literature listed separately from human genetics. Datasources: europepmc.","source":{"label":"Open Targets: CSF1R in metastatic neoplasm","url":"https://platform.opentargets.org/evidence/ENSG00000182578/MONDO_0024883","date":"2026-11-11T18:00:33.483Z"}},{"label":"KIT (via Pazopanib)","text":"Evidence types in metastatic neoplasm: literature; literature listed separately from human genetics. Datasources: europepmc.","source":{"label":"Open Targets: KIT in metastatic neoplasm","url":"https://platform.opentargets.org/evidence/ENSG00000157404/MONDO_0024883","date":"2026-11-11T18:00:33.483Z"}},{"label":"LCK (via Pazopanib)","text":"Evidence types in metastatic neoplasm: literature; literature listed separately from human genetics. Datasources: europepmc.","source":{"label":"Open Targets: LCK in metastatic neoplasm","url":"https://platform.opentargets.org/evidence/ENSG00000182866/MONDO_0024883","date":"2026-11-11T18:00:33.483Z"}}],"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":"Single group","rule":"Registry allocation field","source":{"label":"ClinicalTrials.gov NCT04199026","url":"https://clinicaltrials.gov/study/NCT04199026","date":"2026-11-11T18:00:33.483Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"yes","detail":"20 planned; each patient moves a rate by 100 ÷ 20 = 5.0 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT04199026","url":"https://clinicaltrials.gov/study/NCT04199026","date":"2026-11-11T18:00:33.483Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Determination of the safety and technical feasibility of microdevice insertion/removal, as assessed by adverse events…; To assess efficacy across all individual agents or drug combinations tested using the microdevice technology.","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT04199026","url":"https://clinicaltrials.gov/study/NCT04199026","date":"2026-11-11T18:00:33.483Z"},"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":"no","detail":"Primary completion expected 2028-12-31; not yet due","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT04199026","url":"https://clinicaltrials.gov/study/NCT04199026","date":"2026-11-11T18:00:33.483Z"},"context":[]}],"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":"728 terminated, withdrawn or suspended trials of drugs against TOP2A; 3 of the 200 most recent give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"TOP2A: what already stopped","url":"/target/ENSG00000131747#stopped","date":"2026-11-11T18:00:33.523Z"}}],"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":"yes","detail":"The only site is in United States","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT04199026","url":"https://clinicaltrials.gov/study/NCT04199026?tab=locations","date":"2026-11-11T18:00:33.483Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-000601-PIP01-09-M06 (pazopanib, Treatment of Ewing sarcoma family of tumours;Treatment of non-rhabdomyosarcoma soft tissue sarcoma;Treatment of rhabdomyosarcoma): PM: decision on the application for modification of an agreed PIP, 11 Sept 2019; compliance positive 24 Jul 2020; EMEA-000019-PIP08-12-M03 (everolimus, Treatment of tuberous sclerosis complex): PM: decision on the application for modification of an agreed PIP, 31 Oct 2017; compliance positive 1 Jun 2018; EMEA-002043-PIP01-16 (doxorubicin hydrochloride, Treatment of hepatocellular carcinoma): W: decision granting a waiver in all age groups for all conditions or indications, 31 Jan 2017; EMEA-000019-PIP11-14 (everolimus, Treatment of thoracic neuroendocrine tumour): W: decision granting a waiver in all age groups for all conditions or indications, 30 Jan 2015; +4 more","rule":"An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-paediatric_investigation_plans-output-json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_orphan","label":"EU orphan designation","value":"yes","detail":"EU/3/25/3056 positive 22 May 2025: Treatment of soft-tissue sarcoma; EU/3/10/764 expired 4 Aug 2010: Treatment of tuberous sclerosis; EU/3/22/2624 positive 21 Jun 2022: Treatment of soft tissue sarcoma; EU/3/10/833 positive 23 Feb 2011: Treatment of hepatocellular carcinoma; +8 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":"Zolsketil pegylated liposomal: authorised since 31 May 2022; Afinitor: authorised since 2 Aug 2009; Caelyx pegylated liposomal: authorised since 20 Jun 1996; Celdoxome pegylated liposomal: lapsed since 15 Sept 2022; +6 more","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":"yes","detail":"Doxorubicin Hydrochloride, 7 Aug 1974: MULTIPLE; Everolimus [Afinitor] &, 29 Oct 2010: Adult and pediatric patients aged 1 year and older with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected","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":"2026-11-11T18:00:33.556Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"678 interventional studies of Doxorubicin Hydrochloride, Everolimus, Ganitumab, Pazopanib include patients under 18; 130 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=%22Doxorubicin+Hydrochloride%22+OR+%22Everolimus%22+OR+%22Ganitumab%22+OR+%22Pazopanib%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T18:00:33.578Z"},"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 NCT04199026","url":"https://clinicaltrials.gov/study/NCT04199026","date":"2026-11-11T18:00:33.483Z"}},{"label":"principal investigator","text":"Joseph Ludwig, MD, M.D. Anderson Cancer Center","source":{"label":"Person page","url":"/person/Joseph%20Ludwig%2C%20MD","date":"2026-11-11T18:00:33.483Z"}}],"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 NCT04199026","url":"https://clinicaltrials.gov/study/NCT04199026","date":"2026-11-11T18:00:33.483Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T18:00:33.483Z"},{"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":"2026-11-11T18:00:33.480Z"}