[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"advanced-small-bowel-adenocarcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:advanced-small-bowel-adenocarcinoma":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,45],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":28,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":44},"100648253","phase-2-sacituzumab-tirumotecan-mk-2870-in-patients-with-advanced-small-bowel-adenocarcinoma-refractory-or-intolerant-to-platinum-based-combination-therapy-100648253",false,"NCT07720258","Sacituzumab Tirumotecan (MK-2870) in Patients With Advanced Small Bowel Adenocarcinoma Refractory or Intolerant to Platinum-Based Combination Therapy","Sacituzumab Tirumotecan (MK-2870) Monotherapy in Patients With Advanced or Metastatic Small Bowel Adenocarcinoma Refractory or Intolerant to Platinum-Based Combination Therapy: A Multicenter, Phase II Investigator-Initiated Registration-directed Trial (METROPOLIS；NCCH2503\u002FMK018)","METROPOLIS","Inclusion Criteria:\n\n1. Has a histologically or cytologically confirmed diagnosis of Small bowel Adenocarcinoma.\n\n   If diagnosed before enrollment, the timing of diagnosis shall not be considered. If this histological diagnosis was performed at the referring institution (i.e., a center not participating in the study), it must be reviewed and verified by a pathologist at the participating study site.\n2. Corresponds to any of the following a) to c)\n\n   1. It has been determined that R0 resection is not possible due to the combined resection of the invasive lesion in locally advanced small bowel adenocarcinoma.\n   2. Diagnosed as small bowel adenocarcinoma with distant metastasis, classified as UICC-TNM stage IV.\n   3. Diagnosed as a postoperative recurrence of small bowel adenocarcinoma.\n3. No Active central nervous system (CNS) metastases-including brain metastases, carcinomatous (leptomeningeal) meningitis, or symptomatic spinal metastases that require radiotherapy or surgical intervention.\n4. No clinically significant pericardial effusion, pleural effusion, or ascites requiring invasive interventions such as drainage is observed.\n5. Age ≥18 years at the time of enrollment.\n6. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n7. At least one target lesion by RECIST version 1.1 identified on contrast-enhanced CT (brain, neck, chest, abdomen, pelvis with ≤5 mm slice thickness) performed within 14 days prior to enrollment (same day of the week within 14 days is acceptable; this applies similarly to other time-based criteria below).\n8. Has been previously treated with platinum combinations (FOLFOX or CapeOX therapy) for locally advanced or metastatic small bowel adenocarcinoma and discontinued due to disease progression, recurrence, or toxicities.\n9. If a genomic alteration that has a tumor-agnostic indication for solid tumors has been identified, the patient must also be refractory to, intolerant of, or ineligible for the corresponding drug (e.g., pembrolizumab for MSI-High or dMMR, or the combination of dabrafenib and trametinib for BRAF V600E mutations).\n10. Archival tumor tissue from either the primary lesion or metastatic lesion is available at the date of enrollment. If archival tumor tissue is not available, consent has been obtained to undergo an additional biopsy to obtain tumor tissue prior to commencement of study drug administration. Assessment of TROP2 expression is mandatory for this study.\n11. No prior treatment with Trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugates or antibody-drug conjugates containing anti-topoisomerase I agents.\n12. No administration of anticancer therapies (e.g., chemotherapy, targeted therapy, immunotherapy) or other investigational products and radiotherapy (including palliative radiotherapy) for the current malignancy within 14 days prior to enrollment.\n13. No major surgery under general anesthesia within 28 days prior to enrollment.\n14. Laboratory values within the following criteria based on testing within 14 days prior to enrollment.:\n\n    1. Neutrophil count≥1,500\u002Fmm3\n    2. Platelet count≥100,000\u002Fmm3\n    3. Hemoglobin≥9.0 g\u002FdL\n    4. AST≤75 U\u002FL(In cases of hepatic metastasis, levels up to 150 U\u002FL are acceptable.)\n    5. ALT≤75U\u002FL(In cases of hepatic metastasis, levels up to 150 U\u002FL are acceptable.)\n    6. Total bilirubin≤1.5 mg\u002FdL\n    7. Calculated CrCl≥30mL\u002Fmin\n15. Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1(except for alopecia and vitiligo). Participants with endocrine-related AEs (e.g., hypothyroidism or adrenal insufficiency) who are adequately treated with hormone replacement therapy are eligible.\n16. For male patients: Must agree to use acceptable contraception※1,2 and refrain from sperm donation for at least 120 days after the last dose of study drug.\n\n    For female patients: Must meet one of the following conditions:\n\n    i) Not of childbearing potential (POCBP)\n\n    ii) If of childbearing potential:\n    * The patient must not be pregnant, and a pregnancy test (high-sensitivity serum or urine β-hCG test) must confirm a negative result within 14 days prior to enrollment. If a negative result cannot be confirmed by a urine test, a serum pregnancy test is required.\n    * Agrees to use effective contraception ※1,2 from the time of informed consent through at least 210 days after the last dose of study drug. If breastfeeding, agrees to discontinue breastfeeding from the first dose of the study drug through at least 10 days after the last dose.\n    * Uses a contraceptive method that is highly effective (with a failure rate of \\\u003C1% per year), with low user dependency, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate the study intervention after the last dose of study intervention. The patient agrees not to donate eggs (ova, oocytes) to others or freeze\u002Fstore eggs during this period for the purpose of reproduction.\n    * The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs include condoms, pessaries or diaphragms, oral contraceptives, and intrauterine devices.\n    * Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy.\n\n      * 1\\. The patient must not be currently pregnant and, when engaging in penile-vaginal intercourse with a partner who is capable of becoming pregnant, must use a condom (male or female type). In addition, because condoms may break or leak, the partner must also use an additional effective contraceptive method.\n      * 2．If the patient is confirmed to be azoospermia-either due to vasectomy or secondary to a medical condition-based on medical records, physical examination, or medical history as documented by site personnel verified by the investigator, additional contraception is not required.\n17. Written informed consent obtained from the patient.\n\nExclusion Criteria:\n\n1. Has a known additional malignancy that is progressing or has required active treatment. However, the following i) to iv) are not excluded.\n\n   i) Completely resected the following cancers: basal cell carcinoma; stage I squamous cell carcinoma; carcinoma in situ; intramucosal carcinoma; non-muscle-invasive bladder cancer.\n\n   ii) Gastrointestinal cancers curatively resected by endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR).\n\n   ⅲ) Localized prostate cancer treated with curative intent and showing no evidence of progression, or low-risk or very low-risk localized prostate cancer (by standard guidelines) either treated with definitive intent or untreated in active surveillance with stable disease.\n\n   iv) Other cancers with no recurrence observed within past three years.\n2. Patients with active gastrointestinal ulcers.\n3. Has a history of pneumonitis\u002Finterstitial lung disease that required steroids or has current pneumonitis\u002Finterstitial lung disease ,or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening.\n4. Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea).\n5. Has a current and past history of documented severe dry eye syndrome, severe Meibomian gland disease and\u002For blepharitis, or severe corneal disease that prevents\u002Fdelays corneal healing.\n6. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to≥480 ms, prior treatment history with cardiotoxic agents and\u002For other serious cardiovascular and cerebrovascular diseases within 6 months before enrollment.\n7. Severe hypersensitivity (Grades ≥3) to study intervention, any of their excipients, and\u002For to another biologic therapy.\n8. Is currently receiving a strong inducer\u002Finhibitor of CYP3A4 that cannot be discontinued for the duration of treatment with study intervention. The required washout period before starting study intervention is 2 weeks.\n\n   Note: A list of strong inducers\u002Finhibitors of CYP3A4 can be found at the following website:https:\u002F\u002Fwww.fda.gov\u002Fdrugs\u002Fdrug-interactions-labeling\u002Fhealthcare-professionals-fdas-examples-drugs-interact-cyp-enzymes-and-transporter-systems\n9. Is currently participating in another therapeutic clinical trial. Concurrent enrollment on another therapeutic clinical trial or any trial designed to impact the efficacy of anti-cancer therapy is prohibited.\n10. Has an active infection requiring systemic therapy.\n11. Positive for HBs antigen, or negative for HBs antigen but positive for either HBs antibody or HBc antibody and positive for HBV DNA quantification. Patients are eligible if they have received antiviral therapy for hepatitis B for at least 4weeks and have HBV DNA is below the lower limit of quantification at the time of enrollment.\n12. Positive for HIV, Positive for HCV RNA, or, if HCV RNA is negative, has not completed curative antiviral therapy at least 28 days prior to enrollment. HCV RNA testing is required only for patients who test positive for HCV antibodies.\n13. Has a history or current evidence of any condition due to a concurrent psychiatric disorder or psychiatric symptoms that interfere with activities of daily living and interfere with the individual's participation.\n14. Received a live or live-attenuated vaccine within 30 days before enrollment. Administration of killed vaccines are allowed.","ALL","18 Years",{"count":20,"type":21},27,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","Small bowel adenocarcinoma is a rare cancer with a poor prognosis. For patients with locally advanced or metastatic disease, the usual first treatment is chemotherapy with platinum-based combinations such as FOLFOX or CapeOX. However, once the cancer grows after this treatment or the side effects become too severe, there is no widely accepted standard second-line therapy, and outcomes are generally poor. New treatment options are therefore urgently needed.\n\nIn a recent translational research study conducted by Fujii, Shoji, et al., immunohistochemical staining for TROP2 was performed in 51 patients with pathologically diagnosed small bowel adenocarcinoma, and TROP2 positivity was confirmed in 43 cases (84.3%). Furthermore, patient-derived organoids were established using tumor tissues obtained from patients with small bowel adenocarcinoma, and the in vitro efficacy of sacituzumab tirumotecan was evaluated. A concentration-dependent growth-inhibitory effect was observed, with significant sensitivity observed in the nanomolar concentration range. Therefore, treatment with sacituzumab tirumotecan targeting TROP2 is expected to improve the prognosis of patients with small bowel adenocarcinoma.\n\nThe METROPOLIS trial is a multicenter, single-arm, phase II investigator-initiated trial designed to evaluate the efficacy and safety of sacituzumab tirumotecan in patients with locally advanced or metastatic small bowel adenocarcinoma that has progressed during or after, or is intolerant to, platinum-based combination chemotherapy (FOLFOX or CapeOX). Eligible patients are adults (aged 18 years or older) with histologically or cytologically confirmed small bowel adenocarcinoma, a good performance status, adequate organ function, and at least one measurable lesion on a CT scan. Patients who have genomic alterations that make them candidates for previously approved \"tumor-agnostic\" targeted drugs (for example, high microsatellite instability or high tumor mutational burden) must already have tried and not benefited from, or not tolerated, those treatments. TROP2 positivity is not required for study participation; however, assessment of TROP2 expression is mandatory for exploratory biomarker analyses.\n\nSacituzumab tirumotecan at 4 mg\u002Fkg is administered intravenously on Days 1 and 15 of each 28-day cycle and continued until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria are met. Tumor scans with contrast-enhanced CT will be performed every 8 weeks up to week 24 and every 12 weeks thereafter to monitor the response of the sacituzumab tirumotecan. The primary objective is to determine the proportion of patients achieving a tumor response to sacituzumab tirumotecan, as assessed by independent radiologic review. Key secondary objectives include progression-free survival, overall survival, duration of response, and safety profiling.\n\nIn addition, this study includes a prespecified translational research program. Tumor samples will be examined for TROP2 using immunohistochemistry, and researchers will investigate the relationship between TROP2 and the effects of sacituzumab tirumotecan. Blood and tissue samples will also be collected before treatment, during treatment, and at the time of cancer progression, when possible, for detailed \"multi-omics\" analyses. These translational studies aim to elucidate why some patients respond whereas others do not, and to identify biomarkers that could inform future treatment strategies for small bowel adenocarcinoma.\n\nThe METROPOLIS trial has been approved by the Institutional Review Board of the National Cancer Center, Japan, as well as by the ethics committees at participating sites. This trial is conducted with funding and sacituzumab tirumotecan supplied by MERCK SHARP \\& DOHME LLC. Enrollment began in January 2027 and is planned to continue through December 2028, with patients followed for at least 12 months after the last participant is enrolled.",[27],"Advanced Small Bowel Adenocarcinoma",[29,30,31],"Sacituzumab Tirumotecan","Small Bowel Adenocarcinoma","Advanced","NOT_YET_RECRUITING","2026-07-17",{"date":35,"type":36},"2026-07-22","ACTUAL",{"date":38,"type":21},"2027-01-01",{"date":40,"type":21},"2029-12-31",{"name":42,"class":43},"National Cancer Center, Japan","OTHER_GOV",5,{"id":46,"slug":47,"hasResults":11,"nctId":48,"briefTitle":49,"officialTitle":50,"acronym":51,"eligibilityCriteria":52,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":53,"targetDuration":4,"studyType":22,"phases":54,"briefSummary":55,"conditions":56,"keywords":57,"overallStatus":61,"whyStopped":4,"lastUpdateSubmitDate":62,"lastUpdatePostDateStruct":63,"startDateStruct":65,"completionDateStruct":67,"leadSponsor":69,"locationsCount":70},"100619645","phase-2-enfortumab-vedotin-in-patients-with-advanced-small-bowel-adenocarcinoma-refractory-or-intolerant-to-platinum-based-combination-therapy-100619645","NCT07347314","Enfortumab Vedotin in Patients With Advanced Small Bowel Adenocarcinoma Refractory or Intolerant to Platinum-based Combination Therapy","Enfortumab Vedotin in Patients With Locally Advanced or Metastatic Small Bowel Adenocarcinoma Refractory or Intolerant to Platinum-based Combination Therapy: a Multicenter, Phase II Investigator-initiated Trial (ENVELOPE, NCCH2412\u002FMK015)","ENVELOPE","Inclusion Criteria:\n\n1. Histologically or cytologically confirmed small bowel adenocarcinoma (duodenum excluding the ampulla of Vater, jejunum, or ileum). If pathology was performed at another institution, slides\u002Fblocks must be reviewed by a pathologist at the study site before enrollment.\n2. One of the following:\n\n   1. unresectable locally advanced small bowel adenocarcinoma in which R0 resection would require combined resection of invaded organs and is judged infeasible\n   2. UICC-TNM stage IV small bowel adenocarcinoma with distant metastasis\n   3. postoperative recurrence of small bowel adenocarcinoma.\n3. No symptomatic brain metastases, carcinomatous meningitis, or spinal metastases requiring radiation or surgical intervention.\n4. No clinically significant pericardial effusion, pleural effusion, or ascites requiring treatment.\n5. Age ≥18 years at registration.\n6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.\n7. ≥1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, on contrast-enhanced CT (slice thickness ≤5 mm) obtained within 14 days before registration.\n8. Prior platinum-based chemotherapy for unresectable locally advanced or metastatic small bowel adenocarcinoma (FOLFOX or CapeOX) with documented progression, recurrence or treatment discontinuation due to toxicity.\n9. If prior testing (e.g., microsatellite instability, mismatch repair, or comprehensive genomic profiling) has identified alterations that qualify for tumor-agnostic approved therapies, the patient must be refractory, intolerant, or ineligible to such therapies. These tests are not mandatory; lack of testing does not preclude enrollment.\n10. Archival tumor tissue is available; if unavailable, the patient agrees to a pre-treatment biopsy to obtain tumor tissue.\n11. No anticancer chemotherapy or radiotherapy within 14 days before registration.\n12. No surgery under general anesthesia within 28 days before registration.\n13. Screening laboratory tests within 14 days before registration meet all of the following conditions:\n\n    1. absolute neutrophil count ≥1,500\u002Fmm³\n    2. platelet count≥100,000\u002Fmm³\n    3. hemoglobin ≥8.5 g\u002FdL\n    4. AST ≤100 U\u002FL (≤200 U\u002FL with liver metastases)\n    5. ALT ≤100 U\u002FL (≤200 U\u002FL with liver metastases)\n    6. total bilirubin ≤1.5 mg\u002FdL\n    7. serum creatinine ≤1.5 mg\u002FdL\n14. Contraception: Women of childbearing potential agree to use effective contraception and to refrain from oocyte donation from consent through ≥2 months after last dose; breastfeeding patients agree to withhold breastfeeding for ≥3 weeks after last dose; men agree to use effective contraception and to refrain from sperm donation from consent until ≥1 month after last dose.\n15. Written informed consent obtained from the patient.\n\nExclusion Criteria:\n\n1. Active second primary malignancy.\n2. Active infection requiring systemic therapy.\n3. Interstitial lung disease\u002Fpneumonitis, diagnosed by imaging or clinical findings, current or prior, irrespective of steroid use.\n4. Poorly controlled diabetes mellitus: HbA1c ≥8%, or HbA1c 7.0-\\\u003C8.0% with otherwise unexplained hyperglycemic symptoms (polyuria and\u002For polydipsia).\n5. Known hypersensitivity to enfortumab vedotin, its excipients (e.g., histidine, trehalose dihydrate, polysorbate 20).\n6. Ongoing grade ≥2 sensory or motor peripheral neuropathy.\n7. Cerebrovascular event, unstable angina, myocardial infarction, or severe heart failure within 6 months before registration.\n8. Ongoing grade ≥2 unresolved clinically significant toxicities from prior therapy, excluding alopecia.\n9. Ongoing grade ≥2 dermatologic disorders regardless of prior-treatment causality.\n10. Ongoing use of chronic systemic corticosteroids or other immunosuppressants.\n11. Active keratitis or corneal ulcer.\n12. Positive for HIV antibodies, HBs antigen, or HCV RNA\n13. Negative for HBs antigen, positive for HBs or HBc antibodies, and positive HBV DNA quantification (patients are not excluded if HBV DNA is detected but below the limit of quantification).\n14. Pregnant or possibly pregnant women.\n15. Psychiatric illness or psychiatric symptoms that interfere with activities of daily living and, in the investigator's judgment, preclude study participation.",{"count":20,"type":21},[24],"Small bowel adenocarcinoma is a rare cancer with a poor prognosis. For patients with locally advanced or metastatic disease, the usual first treatment is chemotherapy with platinum-based combinations such as FOLFOX or CapeOX. However, once the cancer grows after this treatment or the side effects become too severe, there is no widely accepted standard second-line therapy, and outcomes are generally poor. New treatment options are therefore urgently needed. Recent retrospective research from our group has shown that the majority of the small bowel adenocarcinomas strongly express a protein called Nectin-4 on the surface of cancer cells. High Nectin-4 expression was also associated with poorer survival, suggesting that Nectin-4 could be a crucial treatment target in this disease.\n\nEnfortumab vedotin is a targeted anticancer drug called an antibody-drug conjugate. It combines an antibody that recognizes Nectin-4 with vedotin, a cytotoxic anticancer agent (payload). After enfortumab vedotin binds to Nectin-4 on the tumor cell surface, it is taken up into the cell and releases the anticancer payload, which damages the cell's internal structure and leads to cell death and apoptosis. Enfortumab vedotin has already shown meaningful antitumor activity and an acceptable safety profile in patients with advanced urothelial carcinoma and is approved over the world. However, its efficacy has never been formally evaluated in patients with small bowel adenocarcinoma.\n\nENVELOPE is a multicenter, single-arm, phase II investigator-initiated trial designed to evaluate the efficacy and safety of enfortumab vedotin in patients with locally advanced or metastatic small bowel adenocarcinoma that has progressed during or after, or is intolerant to, platinum-based combination chemotherapy (FOLFOX or CapeOX). Eligible patients are adults (aged 18 years or older) with histologically or cytologically confirmed small bowel adenocarcinoma, a good performance status, adequate organ function, and at least one measurable lesion on a CT scan. Patients who have genomic alterations that make them candidates for previously approved \"tumor-agnostic\" targeted drugs (for example, high microsatellite instability or high tumor mutational burden) must already have tried and not benefited from, or not tolerated, those treatments. Testing positive for Nectin-4 is not required to take part in this study.\n\nParticipants will receive enfortumab vedotin as an intravenous infusion at a dose of 1.25 mg\u002Fkg on days 1, 8, and 15 of each 28-day treatment cycle. Treatment will continue as long as the cancer does not grow and side effects remain manageable. Tumor scans with contrast-enhanced CT will be performed every 8 weeks up to week 24 and every 12 weeks thereafter to monitor the response of the enfortumab vedotin. The primary objective is to determine the proportion of patients achieving a tumor response to enfortumab vedotin, as assessed by independent radiologic review. Key secondary objectives include progression-free survival, overall survival, duration of response, and safety profiling.\n\nIn addition, this study includes a prespecified translational research program. Tumor samples will be examined for Nectin-4 expression using immunohistochemistry, and researchers will investigate the relationship between Nectin-4 levels and the effects of enfortumab vedotin. Blood and tissue samples will also be collected before treatment, during treatment, and at the time of cancer progression, when possible, for detailed \"multi-omics\" analyses. These translational studies aim to elucidate why some patients respond whereas others do not, and to identify biomarkers that could inform future treatment strategies for small bowel adenocarcinoma.\n\nThe ENVELOPE trial has been approved by the Institutional Review Board of the National Cancer Center, Japan, as well as by the ethics committees at participating sites. The study is funded by the Japan Agency for Medical Research and Development (AMED), and enfortumab vedotin is supplied by Astellas Pharma. Enrollment began in October 2025 and is planned to continue through October 2027, with patients followed for at least 12 months after the last participant is enrolled.",[27],[58,59,60],"enfortumab vedotin","small bowel adenocarcinoma","advanced","RECRUITING","2026-03-10",{"date":64,"type":36},"2026-03-11",{"date":66,"type":36},"2025-11-04",{"date":68,"type":21},"2028-09-30",{"name":42,"class":43},3]