Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Sarcoma, Ewing

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Ewing Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Irinotecan

Trabectedin

Alovudine

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antiviral Agents

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.

Patients with Ewing sarcoma will be administered trabectedin intravenously. Cycles are 21 days.

Trabectedin 1 MG [Yondelis]

Patients with Ewing sarcoma will be administered inirotecan intravenously. Cycles are 21 days.

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.

tumor biopsy

Some patients will receive PET scans with the use of 18F-FLT, a radioactive tracer, performed at the National Institute of Health.

3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging

Patrick Grohar, MD/PhD

John Glod, MD/PhD

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.

Phase I was completed on 11/16/2022. Phase II is actively recruiting.

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.

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.

SARC037: A Phase I/II Study to Evaluate the Safety of Trabectedin in Combination With Irinotecan in Ewing Sarcoma Patients

SARC037: A Phase I/II Study to Evaluate the Safety of Trabectedin Administered as a 1-Hour Infusion in Ewing Sarcoma Patients in Combination With Low Dose Irinotecan and 3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging

The time from starting treatment until disease progression

To determine the rate of disease progression at 6 months after starting treatment

The time from tumor response to disease progression

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).

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

Tumor objective response rate (ORR) assessed by RECIST v1.1.

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.

18F-FLT PET avidity of Ewing sarcoma tumors.

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.

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.

Spots Global Cancer Trial Database for trabectedin 1 mg [yondelis]