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Therapy Name | Sirolimus |
Synonyms | |
Therapy Description |
Rapamune (sirolimus) binds to the FKBP-12 to generate an immunosuppressive complex that binds and allosterically inhibits mTOR (PMID: 25261369). Rapamune (sirolimus) is FDA approved for the prevention of renal transplant rejection and for patients with lymphangioleiomyomatosis (FDA.gov). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
Sirolimus | Rapamune | Rapamycin | mTORC1 Inhibitor 9 | Rapamune (sirolimus) binds to the FKBP-12 to generate an immunosuppressive complex that binds and allosterically inhibits mTOR (PMID: 25261369). Rapamune (sirolimus) is FDA approved for the prevention of renal transplant rejection and for patients with lymphangioleiomyomatosis (FDA.gov). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
PIK3CA E542K PTEN loss | stomach cancer | unknown | Sirolimus | Phase 0 | Actionable | In a pilot clinical trial, Rapamune (sirolimus) demonstrated modest clinical activity in patients with PIK3CA-mutant gastric cancer (n=3) or hilar cholangiocarcinoma (n=1), including a gastric cancer patient harboring PIK3CA E542K and PTEN loss, with a 0% response rate, median progression-free survival of 1.9 months, and median overall survival of 3.6 months (PMID: 28685070). | 28685070 |
APC inact mut | colon cancer | sensitive | Sirolimus | Preclinical | Actionable | In preclinical trials, Sirolimus (rapamycin) was shown effective in reducing tumors in mouse models of familial adenomatous polyposis and colon cancer with APC deficient tumors (PMID: 18768809, PMID: 20080688). | 18768809 20080688 |
PIK3CA E545K PTEN loss | stomach cancer | unknown | Sirolimus | Phase 0 | Actionable | In a pilot clinical trial, Rapamune (sirolimus) demonstrated modest clinical activity in patients with PIK3CA-mutant gastric cancer (n=3) or hilar cholangiocarcinoma (n=1), including 2 gastric cancer patients harboring PIK3CA E545K and PTEN loss, with a 0% response rate, median progression-free survival of 1.9 months, and median overall survival of 3.6 months (PMID: 28685070). | 28685070 |
FBXW7 E192A | fibrolamellar carcinoma | predicted - sensitive | Sirolimus | Case Reports/Case Series | Actionable | In a Phase I study, Rapamune (sirolimus) resulted in prolonged stable disease in a patient with hepatocellular fibrolamellar carcinoma harboring FBXW7 E192A (PMID: 24586741). | 24586741 |
PIK3CA C420R | Advanced Solid Tumor | sensitive | Sirolimus | Preclinical | Actionable | In a preclinical study, cells expressing PIK3CA C420R were sensitive to Rapamune (sirolimus) in culture (PMID: 17376864). | 17376864 |
PIK3CA I391M | uterine cancer | predicted - sensitive | Sirolimus | Case Reports/Case Series | Actionable | In a clinical case study, a uterine cancer patient harboring PIK3CA I391M demonstrated stable disease when treated with Rapamune (sirolimus) (PMID: 28514312). | 28514312 |
PIK3CA E542K | Advanced Solid Tumor | sensitive | Sirolimus | Preclinical | Actionable | In a preclinical study, Rapamune (sirolimus) demonstrated efficacy in inhibiting transformation of cultured cells containing PIK3CA E542K mutations (PMID: 15647370). | 15647370 |
FBXW7 inact mut | breast cancer | sensitive | Sirolimus | Preclinical - Cell line xenograft | Actionable | In a preclinical study, breast cancer cells harboring a FBXW7 mutation demonstrated sensitivity to Rapamune (sirolimus) in culture and in cell line xenograft models (PMID: 18787170). | 18787170 |
PIK3CA M1043V | Advanced Solid Tumor | sensitive | Sirolimus | Preclinical | Actionable | In a preclinical study, Rapamune (sirolimus) inhibited proliferation in cultured cells expressing PIK3CA M1043V (PMID: 17376864). | 17376864 |
PIK3CA H1047R | lung adenocarcinoma | no benefit | Sirolimus | Preclinical | Actionable | In a preclinical study, Sirolimus (rapamycin) failed to inhibit tumor growth in a mouse lung adenocarcinoma model expressing the PIK3CA H1047R mutation (PMID: 19029981). | 19029981 |
PIK3CA H1047R | Advanced Solid Tumor | sensitive | Sirolimus | Preclinical | Actionable | In a preclinical study, transformed cells expressing PIK3CA H1047R were sensitive to Rapamune (sirolimus), resulting in inhibition of transformation in culture (PMID: 15647370). | 15647370 |
FBXW7 loss | colon cancer | sensitive | Sirolimus | Preclinical | Actionable | In a preclinical study, Rapamune (sirolimus) inhibited epithelial-mesenchymal transition, motility, and invasiveness in colon cancer cells lacking FBXW7 in culture (PMID: 23558291) | 23558291 |
PIK3CA E545K | breast cancer | sensitive | Sirolimus | Preclinical - Cell culture | Actionable | In a preclinical study, a breast cancer cell line harboring PIK3CA E545K demonstrated hypersensitivity to Rapamune (sirolimus)-induced growth inhibition in culture (PMID: 24631838). | 24631838 |
PIK3CA mutant | Erdheim-Chester disease | sensitive | Sirolimus | Guideline | Actionable | Rapamune (sirolimus) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring PIK3CA mutations (NCCN.org). | detail... |
PIK3CA E545K | Advanced Solid Tumor | sensitive | Sirolimus | Preclinical | Actionable | In a preclinical study, Rapamune (sirolimus) demonstrated efficacy in inhibiting transformation of cultured cells containing PIK3CA E545K mutations (PMID: 15647370). | 15647370 |
RB1 loss | neuroendocrine tumor | sensitive | Sirolimus | Preclinical | Actionable | In a preclinical study, Sirolimus (rapamycin) slowed pituitary tumors and decreased the occurrence of thyroid tumors in Rb1+/- mice (PMID: 23454836). | 23454836 |
RB1 loss | retinoblastoma | sensitive | Sirolimus | Preclinical | Actionable | In a preclinical study, Sirolimus (rapamycin) decreased tumor occurrence, tumor hypoxia and tumor vascularization in a retinoblastoma mouse model with functionally inactivated Rb protein (PMID: 21468343, PMID: 1689463). | 21468343 1689463 |
PIK3CA E545K | Klatskin's tumor | unknown | Sirolimus | Phase 0 | Actionable | In a pilot clinical trial, Rapamune (sirolimus) demonstrated modest clinical activity in patients with PIK3CA-mutant gastric cancer (n=3) or hilar cholangiocarcinoma (n=1; harboring PIK3CA E545K), with a 0% response rate, median progression-free survival of 1.9 months, and median overall survival of 3.6 months (PMID: 28685070). | 28685070 |
PIK3CA H1047R | lung cancer | no benefit | Sirolimus | Preclinical | Actionable | In a preclinical study, Sirolimus (rapamycin) did not induce tumor shrinkage in mouse lung cancer models carrying PIK3CA H1047R (PMID: 19029981). | 19029981 |
TSC1 loss | urinary bladder cancer | sensitive | Sirolimus | Preclinical | Actionable | In a preclinical study, Rapamune (sirolimus) inhibited proliferation of cultured bladder cancer cells lacking TSC1 (PMID: 23401075). | 23401075 |
PTEN loss | osteosarcoma | sensitive | Sirolimus | Preclinical - Pdx | Actionable | In a preclinical study, a patient derived xenograft (PDX) model of osteosarcoma with biallelic PTEN loss was sensitive to treatment with Rapamune (sirolimus), demonstrating reduced tumor growth and increased apoptotic activity (PMID: 30266815). | 30266815 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT02009332 | Phase Ib/II | Sirolimus | Phase 1/2 Study of ABI-009 in Nonmuscle Invasive Bladder Cancer | Completed | USA | 0 |
NCT03363763 | Phase II | Sirolimus | Topical Sirolimus Ointment for Cutaneous Angiofibromas in Subjects With Tuberous Sclerosis Complex | Terminated | USA | 1 |
NCT03298958 | Phase III | Sirolimus | Secondary Prevention Trial of Rapamycin in Patients With Resected Non-muscle Invasive Bladder Cancer | Withdrawn | USA | 0 |
NCT04393454 | Phase II | Sirolimus | Study to Evaluate the Efficacy and Safety of Sirolimus in Subjects With Metastatic, Mismatch Repair Deficient Solid Tumors After Immunotherapy | Terminated | USA | 0 |
NCT02790515 | Phase II | Sirolimus anti-thymocyte globulin Blinatumomab Tacrolimus Thiotepa Melphalan Fludarabine Cyclophosphamide Mesna Rituximab Filgrastim | Provision of TCRgammadelta T Cells and Memory T Cells Plus Selected Use of Blinatumomab in Naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation | Active, not recruiting | USA | 0 |
NCT02753309 | Phase 0 | Sirolimus | A Study of Rapamycin Combined With Intravesical BCG in Patients With Non-muscle Invasive Bladder Cancer | Completed | USA | 0 |
NCT01231412 | Phase III | Sirolimus Fludarabine Cyclosporine + Mycophenolate mofetil | Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant | Completed | USA | DNK | DEU | 0 |
NCT00602693 | Phase I | Sirolimus Allopurinol + Cyclophosphamide + Fludarabine | T-Regulatory Cell Infusion Post Umbilical Cord Blood Transplant in Patients With Advanced Hematologic Cancer | Completed | USA | 0 |
NCT02551718 | Phase I | Bosutinib Irinotecan Romidepsin Busulfan Melphalan Nilotinib Crizotinib Cytarabine Mitoxantrone Dasatinib Pazopanib Paclitaxel Clofarabine Hydroxyurea Tretinoin Carfilzomib Nelarabine Bexarotene Pentostatin Everolimus Cabozantinib Mercaptopurine Methotrexate Cladribine Thioguanine Daunorubicin Ponatinib Etoposide Afatinib Gefitinib Gemcitabine Regorafenib Arsenic trioxide Trametinib Imatinib Erlotinib Dabrafenib Decitabine Axitinib Azacitidine Ruxolitinib Fludarabine Lapatinib Ceritinib Sirolimus Sorafenib Lomustine Sunitinib Cabazitaxel Temsirolimus Topotecan Bortezomib Pralatrexate | High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia | Completed | USA | 0 |
NCT02722668 | Phase II | Cyclophosphamide + Fludarabine + Mycophenolate mofetil Sirolimus anti-thymocyte globulin | UCB Transplant for Hematological Diseases Using a Non Myeloablative Prep | Active, not recruiting | USA | 0 |
NCT01087554 | Phase I | Temsirolimus Everolimus Sirolimus Vorinostat | Sirolimus or Everolimus or Temsirolimus and Vorinostat in Advanced Cancer | Active, not recruiting | USA | 0 |
NCT06287944 | Phase I | Melphalan Fludarabine Sirolimus 225Ac-DOTA-Daratumumab Tacrolimus | 225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody With Fludarabine, Melphalan and Total Marrow and Lymphoid Irradiation as Conditioning Treatment for Donor Stem Cell Transplant in Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome | Not yet recruiting | USA | 0 |
NCT01843998 | Phase II | Sirolimus | Therapeutic Efficacy of Topical Sirolimus in Early Stage Cutaneous T-cell Lymphoma (CTCL) | Withdrawn | USA | 0 |
NCT01522820 | Phase I | Rasdegafusp alfa Sirolimus | Vaccine Therapy With or Without Sirolimus in Treating Patients With NY-ESO-1 Expressing Solid Tumors | Completed | USA | 0 |
NCT00923845 | Phase II | Sirolimus Cyclophosphamide + Pentostatin | Low-Intensity Stem Cell Transplantation With Multiple Lymphocyte Infusions to Treat Advanced Kidney Cancer | Completed | USA | 0 |
NCT03826628 | Phase II | Sirolimus | Dose-Ranging Efficacy and Safety Study of Topical Rapamycin Cream for Facial Angiofibroma Associated With Tuberous Sclerosis Complex | Completed | USA | SVK | NZL | HUN | ESP | CZE | AUS | 2 |
NCT01265030 | Phase Ib/II | Sirolimus | A Pilot Study Evaluating the Use of mTor Inhibitor Sirolimus in Children and Young Adults With Desmoid-Type Fibromatosis | Completed | USA | 0 |
NCT03878524 | Phase I | Oxaliplatin Palbociclib Vemurafenib Sirolimus Tretinoin Celecoxib Ipilimumab Ruxolitinib Dasatinib Abiraterone Idelalisib Trametinib Imatinib Erlotinib Carboplatin Olaparib Panobinostat Bortezomib Afatinib Fluorouracil Vorinostat Pembrolizumab Leucovorin Enzalutamide Ponatinib Nivolumab Everolimus Sunitinib Cabazitaxel Cabozantinib Lenvatinib Pertuzumab Sorafenib Venetoclax Bevacizumab | A Personalized Medicine Study for Patients With Advanced Cancer of the Breast, Prostate, Pancreas or Those With Refractory Acute Myelogenous Leukemia (SMMART) | Terminated | USA | 0 |
NCT01163357 | Phase I | Sirolimus Bortezomib + Fludarabine + Melphalan | Bortezomib, Total Marrow Irradiation, Fludarabine Phosphate, and Melphalan in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant For High-Risk Stage I or II Multiple Myeloma | Active, not recruiting | USA | 0 |
NCT02793544 | Phase II | Cyclophosphamide Busulfan Sirolimus Mycophenolate mofetil Mesna Fludarabine | HLA-Mismatched Unrelated Donor Bone Marrow Transplantation With Post-Transplantation Cyclophosphamide | Completed | USA | 0 |
NCT02145559 | Phase I | Metformin + Sirolimus Sirolimus | A Pharmacodynamic Study of Sirolimus and Metformin in Patients With Advanced Solid Tumors | Completed | USA | 0 |
NCT01791088 | Phase I | Sirolimus | Sirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed By Surgery | Completed | USA | 0 |
NCT00305682 | Phase II | Sirolimus Mycophenolate mofetil anti-thymocyte globulin Cyclophosphamide Fludarabine | Non-Myeloablative Conditioning for Unrelated Donor Umbilical Cord Blood Transplant | Completed | USA | 0 |
NCT01195922 | Phase Ib/II | Sirolimus | Rapamycin Therapy in Head and Neck Squamous Cell Carcinoma | Completed | USA | 0 |
NCT02423915 | Phase Ib/II | Filgrastim Rituximab Cyclophosphamide + Fludarabine + Mycophenolate mofetil Sirolimus | Fucosylated T Cells for Graft Versus Host Disease (GVHD) Prevention | Completed | USA | 0 |
NCT00092222 | Phase II | Sirolimus Alpha 2 Interferon Cyclophosphamide + Doxorubicin + Etoposide + Prednisone + Vincristine Sulfate Rituximab Bortezomib Pegylated liposomal doxorubicin | Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity | Active, not recruiting | USA | 0 |
NCT00513474 | Phase I | Rasburicase Methotrexate Sirolimus Cyclosporine Tacrolimus Filgrastim Busulfan + Cyclophosphamide + Etoposide | Rasburicase in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer or Other Disease Undergoing Donor Stem Cell Transplant | Completed | USA | 0 |
NCT02756572 | Phase I | Sirolimus Mycophenolate mofetil Cyclosporine Cytarabine Melphalan Cladribine Filgrastim mitoxantrone hydrochloride Fludarabine | Early Allogeneic Hematopoietic Cell Transplantation in Treating Patients With Relapsed or Refractory High-Grade Myelodysplastic Syndrome or Acute Myeloid Leukemia | Completed | USA | 0 |
NCT01203722 | Phase Ib/II | Tacrolimus Sirolimus Cyclophosphamide + Fludarabine + Mycophenolate mofetil | Reduced Intensity, Partially HLA Mismatched BMT to Treat Hematologic Malignancies | Recruiting | USA | 0 |
NCT01331135 | Phase I | Sirolimus | Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors | Completed | USA | 0 |
NCT01853423 | Phase I | Sirolimus | Tuberou Sclerosis Complex: Facial Angiofibroma Skin Cream | Completed | USA | 0 |
NCT01658007 | Phase I | Sirolimus | Pilot Study Of Sirolimus Plus Multiagent Chemotherapy For Relapsed/Refractory Acute Lymphoblastic Leukemia/Lymphoma | Terminated | USA | 0 |
NCT02110069 | Phase II | Vincristine Sulfate Sirolimus | A Study to Compare Vincristine to Sirolimus for Treatment of High Risk Vascular Tumors | Terminated | USA | 0 |