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| ID | Type | Description | Link |
|---|---|---|---|
| U01CA236220 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Janssen Scientific Affairs, LLC | INDUSTRY |
| National Institutes of Health (NIH) | NIH |
| National Cancer Institute (NCI) | NIH |
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This study evaluates the trabectedin and irinotecan in the treatment of Ewings sarcoma, with a EWS-FLI1 mutation. Patients will also receive an infusion of 18F-FLT in combination with a Positron Emission Tomography (PET) scan to help evaluate the effect of treatment.
Trabectedin and Irinotecan may inhibit the activity of this Ewing sarcoma mutation. Trabectedin may suppress the proliferation of the gene involved in DNA damage response. It blocks EWS-FLI1 by inactivating the fusion protein and silences the target genes.
Irinotecan also suppresses the genes regulating the tumor cells, generating DNA damage. Together, these drugs work in combination to suppress the gene regulating the tumor cells. This combination may suppress the activity of the tumor regulating genes, disrupting the activity of the genes. The infusion of 18F-FLT in combination with a Positron Emission Tomography (PET) scan will demonstrate whether the target cells have been suppressed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Trabectedin and Irinotecan | Experimental | Trabectedin will be delivered by infusion on day 1 followed by 2 doses on irinotecan delivered by infusion for one hour on day 2 and day 4 of 21 day cycles. Some patients will receive an 18F-FLT Imaging scan prior to the first administration of trabectedin and once after administration of trabectedin. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Trabectedin 1 MG [Yondelis] | Drug | Patients with Ewing sarcoma will be administered trabectedin intravenously. Cycles are 21 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase I The recommended dose (RD) of trabectedin administered in combination with low dose irinotecan | The recommended dose will be established by enrolling patients at the lowest dose and observing them for dose limiting toxicity. Dose limiting toxicity describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. The maximum tolerated dose is the highest dose of a drug or treatment that does not cause unacceptable side effects. If 0 of the first 3 subjects experience DLT, the study will proceed to the next dose level. If 1 subject experiences a DLT, that dose level cohort will be expanded to 6 total subjects. If no additional subjects experience DLTs at that dose level cohort, the study will proceed to enroll the next dose level cohort. If ≥ 2 of 6 subjects experience DLT, then that dose level is the recommended dose of trabectedin (RD). The study will proceed to the same process for the irinotecan escalation. If 2 or all 3 subjects experience DLT, that dose level is the recommended dose of trabectedin (RD). | up to 36 months |
| Phase I Tumor response rate | The anti-tumor activity of the combination of trabectedin and low-dose irinotecan as measured by the tumor objective response rate (ORR) assessed by RECIST v1.1 | up to 36 months |
| Phase 2 To determine anti-tumor activity of the combination trabectedin and low-dose irinotecan | Tumor objective response rate (ORR) assessed by RECIST v1.1. | up to 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| Phase I/Phase 2 Tumor response rate, progression-free survival (PFS), duration of response, and 6-month PFS rate of patients with ES treated with trabectedin and irinotecan. | The percentage of patients whose tumor shrinks or disappears after treatment (per RECIST 1.1), progression-free survival (PFS) of patients with ES treated with trabectedin and irinotecan. | up to 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| Progression free survival | The time from starting treatment until disease progression | up to 5 years |
| 6- month Progression free survival | To determine the rate of disease progression at 6 months after starting treatment |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Patrick Grohar, MD/PhD | Children's Hospital of Philadelphia | Principal Investigator |
| John Glod, MD/PhD | National Cancer Institute (NCI) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Los Angeles | Los Angeles | California | 90027 | United States | ||
| National Cancer Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41991689 | Derived | Grohar PJ, Heise R, Wedekind MF, Ballman K, Mascarenhas L, DuBois SG, Maki RG, Boguslawski EA, Gedminas JM, Wilson ER, Thomas E, Segers B, Surrey LF, Ricker C, Klega K, Navid F, Lam GY, The S, Kaufman R, Roberts RD, Hayashi M, Mena E, Overman L, Peer C, Schmidt K, Diamond MS, Figg WD, Bagatell R, Liza Lindenberg M, Choyke PL, Crompton BD, Widemann BC, Glod JW, Laetsch TW, Reinke DK, Chugh R. Trabectedin and low-dose irinotecan to target EWS::FLI1 in Ewing sarcoma: a phase 1/2 trial. Nat Med. 2026 Jun;32(6):2227-2237. doi: 10.1038/s41591-026-04340-7. Epub 2026 Apr 16. |
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This phase I study will follow a standard 3+3 design and the Phase II study will be a single-arm, mini-max Simon two-stage design.
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| Irinotecan | Drug | Patients with Ewing sarcoma will be administered inirotecan intravenously. Cycles are 21 days. |
|
| tumor biopsy | Diagnostic Test | Tumor tissue samples will be collected collected at two timepoints. The first biopsy will be prior to treatment. If a biopsy is not possible archival tissue may be submitted. A second tumor biopsy will be taken fro consenting patients when possible after the first administration of Trabectedin to evaluate the effect on the tumor cells. |
|
| 3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging | Other | Some patients will receive PET scans with the use of 18F-FLT, a radioactive tracer, performed at the National Institute of Health. |
|
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| Phase I monitor the avidity of Ewing sarcoma tumors of EWS-FLI1 12-24 hours after trabectedin administration and before irinotecan is administered and before 18F-FLT PET scans | 18F-FLT PET avidity of Ewing sarcoma tumors. | up to 36 months |
| Phase 2 To determine anti-tumor activity of the combination trabectedin and low-dose irinotecan | The anti-tumor activity of the combination of trabectedin and low-dose irinotecan as measured by the tumor objective response rate (ORR) assessed by RECIST v1.1 | up to 36 months |
| Phase I/Phase 2 Tumor response rate, progression-free survival (PFS), duration of response, and 6-month PFS rate of patients with ES treated with trabectedin and irinotecan. | The percentage of patients whose tumor shrinks or disappears after treatment (per RECIST 1.1) duration of response of patients with ES treated with trabectedin and irinotecan. | up to 36 months |
| Phase I/Phase 2 Tumor response rate, progression-free survival (PFS), duration of response, and 6-month PFS rate of patients with ES treated with trabectedin and irinotecan. | The percentage of patients whose tumor shrinks or disappears after treatment (per RECIST 1.1) duration of 6-month PFS rate ES treated with trabectedin and irinotecan. | up to 36 months |
| up to 36 months |
| Duration of Response | The time from tumor response to disease progression | up to 5 years |
| Bethesda |
| Maryland |
| 20892 |
| United States |
| Boston Children's Hospital / Dana Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| University of Michigan | Ann Arbor | Michigan | 48106 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19105 | United States |
| ID | Term |
|---|---|
| D012512 | Sarcoma, Ewing |
| ID | Term |
|---|---|
| D012516 | Osteosarcoma |
| D018213 | Neoplasms, Bone Tissue |
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D012509 | Sarcoma |
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| ID | Term |
|---|---|
| D000077606 | Trabectedin |
| D000077146 | Irinotecan |
| C002854 | alovudine |
| D014965 | X-Rays |
| ID | Term |
|---|---|
| D004149 | Dioxoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D044005 | Tetrahydroisoquinolines |
| D007546 | Isoquinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D060733 | Electromagnetic Radiation |
| D055590 | Electromagnetic Phenomena |
| D060328 | Magnetic Phenomena |
| D055585 | Physical Phenomena |
| D011827 | Radiation |
| D011839 | Radiation, Ionizing |
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