TABLE 1.
Efficacy results of the 62 fully or partially published early phase trials for recurrent/refractory Ewing sarcoma
| Number/ID | Intervention | Age (years) | Number of ES patients | CR | PR | SD | PD | RR (%) | DCR (%) | 4‐months PFS (%) | 6‐months PFS (%) | Median PFS (months) | 6‐months OS (%) | 1‐year OS (%) | 2‐year OS (%) | Median OS (months) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT00474760 + | Figitumumab | 12–63 | 16 | 1 | 1 | 6 | 5 | 15 | 62 | . | . | 5.6 | . | . | . | . |
| NCT00642941 + | R1507 | >2 | 115 | 1 | 10 | 8 | 96 | 10 | 17 | 11 | 9 | 1.3 | 60 | 35 | 10 | 7.6 |
| NCT00617890 + | Robatumumab | 9–79 | 100 | 6 | 0 | 23 | 55 | 7 | 35 | . | . | . | 75 | 55 | 16 | 6.9 |
| NCT00563680 | Ganitumab | >16 | 22 | 0 | 1 | 7 | 10 | 6 | 44 | . | . | <2 | . | . | . | . |
| NCT00609141 | Cixutumumab | <21 | 35 | 0 | 3 | 5 | 27 | 9 | 23 | . | . | 1.5 | . | . | . | . |
| NCT00668148 | Cixutumumab | >12 | 18 | 0 | 1 | 5 | 13 | 6 | 33 | 27.3 | 11 | 1.5 | 77.8 | . | . | 6 |
| NCT00560235 | Figitumumab | 10–25 | 107 | 0 | 15 | 25 | 66 | 14 | 38 | 25 | 2 | 1.9 | 60 | 35 | 2 | 8.9 |
| NCT01016015 | Temsirolimus + cixutumumab | >16 | 27 | 0 | 4 | 0 | 23 | 15 | 15 | . | . | 7.5 | . | . | . | 16.2 |
| NCT01614795 | Cixutumumab + temsirolimus | <30 | 12 | 0 | 0 | 1 | 10 | 0 | 9 | . | . | . | . | . | . | . |
| NCT02304458 a | Nivolumab with or without ipilimumab | 1–30 | 10 | 0 | 0 | 0 | 10 | 0 | 0 | . | . | . | . | . | . | . |
| NCT02301039 | Pembrolizumab | 16–81 | 13 | 0 | 0 | 2 | 11 | 0 | 15 | . | . | . | . | . | . | . |
| NCT02541604 a | Atezolizumab | 2–29 | 11 | 0 | 0 | 0 | 11 | 0 | 0 | . | . | . | . | . | . | . |
| NCT00357500 | Etoposide, cyclophosphamide + thalidomide, celecoxib | <22 | 4 | 0 | 0 | 1 | 0 | . | . | 8.3 | 0 | 3 | 4 | 12 | 0 | 7 |
| NCT00073983 | Gemcitabine + docetaxel | 13–77 | 14 | 0 | 2 | 6 | 6 | 14 | 57 | . | . | . | . | . | . | . |
| UMIN000001037 a + | Topotecan and ifosfamide | 1–28 | 6 | 1 | 0 | 2 | 3 | . | . | . | . | . | . | . | . | . |
| NCT01380275 + | Docetaxel + irinotecan | <30 | 10 | 1 | 2 | 1 | 5 | 30 | 40 | 33 | 33 | 2.2 | . | . | . | . |
| NCT00807261 | Docetaxel and fixed‐dose rate gemcitabine | >16 | 7 | 0 | 1 | 2 | 2 | . | . | . | . | . | . | . | . | . |
| NCT01141244 + | Temsirolimus, irinotecan and temozolomide | <22 | 7 | 0 | 1 | 1 | 5 | . | . | . | . | . | . | . | . | . |
| NCT02116777 | Talazoparib + temozolomide | 4–25 | 10 | 0 | 0 | 2 | 8 | 0 | 20 | . | . | . | . | . | . | |
| NCT00516295 a | Vincristine+topotecan+cyclophosphamide with bevacizumab | 12–20 | 7 | . | . | . | . | . | . | . | . | 14.7 | . | . | . | . |
| NCT00331643 | Ixabepilone | 3–35 | 16 | 0 | 0 | 1 | 15 | 0 | 6 | . | . | <2.2 | . | . | . | . |
| NCT00470275 | Cytarabine | <30 | 10 | 0 | 0 | 1 | 9 | 0 | 10 | . | . | <1.5 | . | . | . | . |
| NCT00520936 | Pemetrexed | 3–23 | 10 | 0 | 0 | 1 | 9 | 0 | 10 | . | . | <1.5 | . | . | . | . |
| NCT00070109 | Trabectedin | <21 | 11 | 0 | 0 | 1 | 9 | 0 | 10 | 9 | 9 | . | . | . | . | . |
| EudraCT: 2005‐003254‐10 | Oral treosulfan | 3–50 | 21 | 0 | 0 | 1 | 20 | 0 | 5 | 0 | 0 | 1.8 | 52 | 2 | . | 6.4 |
| NCT01222767 | Zalypsis® (PM00104) | 15–53 | 17 | 0 | 0 | 4 | 12 | 0 | 25 | 28.6 | . | 1.8 | . | . | . | . |
| NCT01610570 | Mithramycin | >1 | 8 | 0 | 0 | 0 | 8 | 0 | 0 | . | . | <2 | . | . | . | . |
| NCT00998361 | Hematopoietic stem cell transplantation | 6–22 | 10 | . | . | . | . | . | . | . | . | . | . | 43 | . | . |
| NCT01804634 + | Reduced intensity conditioning and haploidentical BMT | 5–26 | 4 | 3 | 1 | 0 | 0 | . | . | . | . | 10 | . | . | . | 14.6 |
| EudraCT: 2012‐000616‐28 a | Linsitinib | >18 | 16 | 0 | 0 | 7 | 7 | 0 | 50 | . | . | 1.3 | . | . | . | 7.1 |
| NCT00923351 a + | Vaccine and R‐hIL‐7 | 1–35 | 21 | . | . | . | . | . | . | . | . | . | . | . | . | 30 |
| NCT00902044 | Her2 chimeric antigen receptor expressing T cells | 7–30 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | . | . | . | . | . | . | 5 |
| None a | Activated haploidentical natural killer cell infusions | 5–17 | 2 | 0 | 1 | 1 | 0 | . | . | . | . | . | . | . | . | . |
| NCT01241162 | Dendritic cell vaccine with or without gemcitabine | <18 | 2 | 0 | 0 | 0 | 1 | 0 | 0 | . | . | . | . | . | . | . |
| NCT00464620 | Dasatinib | >13 | 17 | 0 | 1 | 0 | 16 | 6 | 6 | 6 | 6 | 1.9 | . | . | 7 | . |
| NCT02048371 a + | Regorafenib | >18 | 30 | 0 | 3 | 18 | 7 | 11 | 75 | 73 | . | 3.6 | . | . | . | . |
| NCT02243605 a + | Cabozantinib‐s‐malate | 13–74 | 45 | 0 | 9 | 10 | 14 | 27 | 58 | . | 24 | . | . | . | . | . |
| NCT01830153 | Everolimus | >18 | 2 | 0 | 0 | 1 | 1 | 0 | . | . | . | . | . | . | . | . |
| NCT01286987 | Talazoparib | >18 | 14 | 0 | 0 | 3 | 9 | 0 | 25 | . | . | . | . | . | . | . |
| NCT01583543 | Olaparib | >18 | 12 | 0 | 0 | 4 | 8 | 0 | 33 | 85 | 35 | 5.7 | . | . | . | . |
| NCT02454972 a | Lurbinectedin | 18–74 | 28 | 0 | 4 | 12 | 12 | 14 | 57 | . | . | 2.8 | . | . | . | . |
| NCT01962103 | Weekly Nab‐paclitaxel | 2–17 | 13 | 1 | 1 | 3 | 7 | 17 | 42 | . | . | . | . | . | . | . |
| NCT01061840 + | Vigil immunotherapy with irinotecan and temozolomide | >2 | 13 | 0 | 1 | 8 | 4 | 8 | 69 | . | . | . | 75 | 73 | 4 | 24 |
| NCT00101270 | Oxaliplatin + irinotecan | <21 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | . | . | . | . | . | . | . |
| NCT00321581 | Cedinarib | 8–18 | 3 | 0 | 1 | 0 | 2 | . | . | . | . | . | . | . | . | . |
| NCT00428272 | Lexatumumab | 2–21 | 4 | 0 | 0 | 0 | 4 | . | . | . | . | . | . | . | . | . |
| NCT00776867 | Perifosine | <21 | 1 | 0 | 0 | 0 | 1 | 0 | . | . | . | . | . | . | . | . |
| NCT00786669 | Bevacizumab and vincristine, irinotecan and temozolomide | <30 | 2 | 1 | 1 | 0 | 0 | . | . | . | . | . | . | . | . | . |
| NCT00927966 | Figitumumab + everolimus | >18 | 1 | 0 | 1 | 0 | 0 | . | . | . | . | . | . | . | . | . |
| NCT00929903 | Pazopanib | 3–24 | 3 | 0 | 0 | 0 | 3 | 0 | . | . | . | . | . | . | . | . |
| NCT01132911 | Vorinostat and bortezomib | <22 | 2 | 0 | 0 | 0 | 2 | 0 | . | . | . | . | . | . | . | . |
| NCT01154816 | Alisertib | 3–21 | 5 | 0 | 0 | 0 | 5 | 0 | . | . | . | . | . | . | . | . |
| NCT01184274 | Pracinostat | <18 | 4 | 0 | 0 | 1 | 3 | 0 | . | . | . | . | . | . | . | . |
| NCT01273090 | Imetelstat sodium | 3–22 | 6 | 0 | 1 | 0 | 5 | . | . | . | . | . | . | . | . | . |
| NCT01353625 a | Oral CC‐115 | >18 | 10 | 0 | 0 | 2 | 8 | 0 | 20 | . | . | . | . | . | . | . |
| NCT01431534 | Ridaforolimus | 8–17 | 3 | 0 | 0 | 0 | 3 | 0 | . | . | . | . | . | . | . | . |
| NCT01431547 | Dalotuzumab +/− ridaforolimus | 3–17 | 7 | 0 | 1 | 0 | 5 | . | . | . | . | . | . | . | . | . |
| NCT01453283 | Trabectedin | 8–16 | 1 | 0 | 0 | 0 | 1 | 0 | . | . | . | . | . | . | . | . |
| NCT01709435 | Cabozantinib S‐Malate | 4–18 | 4 | 0 | 0 | 1 | 3 | . | . | . | . | 5.2 | . | . | . | 9.8 |
| NCT01748721 | MORAb‐004 | 3–21 | 5 | 0 | 0 | 0 | 4 | . | . | . | . | . | . | . | . | . |
| NCT02171260 | Eribulin mesylate | 3–17 | 4 | 0 | 1 | 0 | 3 | . | . | . | . | . | . | . | . | . |
| NCT01331135 | Sirolimus + VP16 + cyclophamide + celecoxib | 1–30 | 3 | 0 | 0 | 0 | 3 | 0 | 0 | 0% | 0 | NA | NA | NA |
RR and DCR were not calculated if <10 patients were analyzed. In orange: part I of phase I/II trials.
Abbreviations: +, positive phase‐I/II trial results; RR, response rate = CR+PR; DCR, disease control rate = CR+PR+SD; mAb, monoclonal antibody; Tox, toxicity; PFS, progression‐free survival; OS, overall survival; CT, chemotherapy; Combo, combination therapy; Ped, pediatric trials; HDC, high‐dose chemotherapy; BMT, bone marrow transplantation; MTKI, multi‐tyrosine kinase inhibitor.
a
Partially published trials.