SARC037: A Phase I Study to Evaluate the Safety of Trabectedin in Combination With Irinotecan in Ewing Sarcoma Patients (U01CA236220)
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| ClinicalTrials.gov Identifier: NCT04067115 |
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Recruitment Status :
Recruiting
First Posted : August 26, 2019
Last Update Posted : May 7, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ewing Sarcoma | Drug: Trabectedin 1 MG [Yondelis] Drug: Irinotecan Diagnostic Test: tumor biopsy Other: 3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 45 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | This phase I study will follow a standard 3+3 design to determine the recommended dose of trabectedin given as a 1-hour infusion in combination with low dose irinotecan. |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | SARC037: A Phase I 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 |
| Actual Study Start Date : | January 5, 2021 |
| Estimated Primary Completion Date : | June 30, 2023 |
| Estimated Study Completion Date : | June 30, 2023 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Trabectedin and Irinotecan
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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Drug: Trabectedin 1 MG [Yondelis]
Patients with Ewing sarcoma will be administered trabectedin intravenously. Cycles are 21 days. Drug: Irinotecan Patients with Ewing sarcoma will be administered inirotecan intravenously. Cycles are 21 days. Diagnostic Test: tumor biopsy 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. Other: 3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging Some patients will receive PET scans with the use of 18F-FLT, a radioactive tracer, performed at the National Institute of Health.
Other Name: 18F-FLT Imaging |
- The recommended dose (RD) of trabectedin administered in combination with low dose irinotecan [ Time Frame: up to 36 months ]
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).
- Tumor response rate [ Time Frame: up to 36 months ]The percentage of patients whose tumor shrinks or disappears after treatment (per RECIST 1.1)
- 18F-FLT PET avidity of Ewing sarcoma tumors. [ Time Frame: up to 36 months ]
- Progression free survival [ Time Frame: up to 5 years ]The time from starting treatment until disease progression
- 6- month Progression free survival [ Time Frame: up to 36 months ]To determine the rate of disease progression at 6 months after starting treatment
- Duration of Response [ Time Frame: up to 5 years ]The time from tumor response to disease progression
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 10 Years to 99 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- diagnosis of relapsed and refractory Ewing sarcoma with EWS-FLI1 fusion type for which there is no known therapy proving to prolong survival
- measurable disease
- ECOG Performance Status of 0-2 or Lansky of 50
- adequate organ function
- written, voluntary consent
- willing to undergo tumor biopsy
- negative hepatitis infection
Exclusion Criteria:
- prior therapy with trabectedin or lurbinectedin
- known history of hypersensitivity to irinotecan or topotecan or their excipients.
- known brain metastases
- known bleeding diathesis
- pregnant or breastfeeding
- currently receiving other investigational drugs or anticancer agents
- clinically significant unrelated illness or uncontrolled infection
- unable to comply with the safety monitoring requirements
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04067115
| Contact: SARC | 7349307600 | sarc@sarctrials.org |
| United States, California | |
| Children's Hospital of Los Angeles | Recruiting |
| Los Angeles, California, United States, 90027 | |
| Contact: Abe Levi, CRSO 323-361-6686 | |
| Principal Investigator: Leo Mascarenhas, MD | |
| United States, Maryland | |
| National Cancer Institute | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
| Principal Investigator: John Glod, MD | |
| United States, Massachusetts | |
| Boston Children's Hospital / Dana Farber Cancer Institute | Not yet recruiting |
| Boston, Massachusetts, United States, 02215 | |
| Principal Investigator: Steven Dubois, MD | |
| United States, Michigan | |
| University of Michigan | Recruiting |
| Ann Arbor, Michigan, United States, 48106 | |
| Principal Investigator: Rashmi Chugh, MD | |
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Principal Investigator: Patrick Grohar, MD/PhD | |
| Principal Investigator: | Patrick Grohar, MD/PhD | Children's Hospital of Philadelphia | |
| Study Director: | John Glod, MD/PhD | National Cancer Institute (NCI) |
| Responsible Party: | Sarcoma Alliance for Research through Collaboration |
| ClinicalTrials.gov Identifier: | NCT04067115 |
| Other Study ID Numbers: |
SARC037 U01CA236220 ( U.S. NIH Grant/Contract ) |
| First Posted: | August 26, 2019 Key Record Dates |
| Last Update Posted: | May 7, 2021 |
| Last Verified: | May 2021 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Sarcoma Sarcoma, Ewing Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Osteosarcoma Neoplasms, Bone Tissue Neoplasms, Connective Tissue Alovudine Irinotecan |
Trabectedin Topoisomerase I Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antineoplastic Agents, Alkylating Alkylating Agents Antiviral Agents Anti-Infective Agents |