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Topoisomerase I inhibitors

Trabectedin + Irinotecan for Ewing Sarcoma (U01CA236220 Trial)

Phase 1 & 2

Waitlist Available

Led By Patrick Grohar, MD/PhD

Research Sponsored by Sarcoma Alliance for Research through Collaboration

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Willing to undergo tumor biopsy

Measurable disease

Must not have

Prior therapy with trabectedin or lurbinectedin

Known brain metastases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Approved for 10 Other Conditions

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial is testing if trabectedin and irinotecan can treat Ewing's sarcoma that has a EWS-FLI1 mutation. Patients will get an infusion of 18F-FLT and have a PET scan to see if the treatment is working.

Who is the study for?

This trial is for patients with relapsed and refractory Ewing sarcoma, specifically the EWS-FLI1 fusion type. Participants must have measurable disease, be in a relatively stable condition (ECOG 0-2 or Lansky ≥50), and agree to undergo tumor biopsies. They should not be pregnant or breastfeeding, have no known therapy that prolongs survival, and must not have used certain drugs like trabectedin.

What is being tested?

The study tests trabectedin combined with irinotecan for treating Ewing sarcoma. It includes an infusion of a diagnostic agent (18F-FLT) followed by PET scans to assess treatment effects. The first phase has been completed; the second phase is now recruiting participants to further evaluate safety and efficacy.

What are the potential side effects?

Potential side effects may include reactions related to organ function due to trabectedin or irinotecan, issues from biopsy procedures such as bleeding or infection risk, and general chemotherapy-related side effects like nausea, fatigue, hair loss, blood cell count changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am willing to have a tumor biopsy.

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My cancer can be measured by tests.

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I can care for myself but may not be able to do heavy physical work.

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My Ewing sarcoma has returned, is resistant to treatment, and has a specific genetic feature.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have previously been treated with trabectedin or lurbinectedin.

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I have cancer that has spread to my brain.

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I have a bleeding disorder.

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I am not taking any experimental drugs or cancer treatments.

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I do not have any severe illnesses or infections that are not under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase I The recommended dose (RD) of trabectedin administered in combination with low dose irinotecan

Phase I Tumor response rate

Secondary study objectives

Phase 2 To determine anti-tumor activity of the combination trabectedin and low-dose irinotecan

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

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.

Other study objectives

6- month Progression free survival

Duration of Response

Progression free survival

Side effects data

From 2020 Phase 2 & 3 trial • 483 Patients • NCT03098030

66%

Anaemia

51%

Neutropenia

28%

Asthenia

26%

Decreased appetite

26%

Neutrophil count decreased

25%

Nausea

25%

Thrombocytopenia

20%

Platelet count decreased

18%

Fatigue

16%

White blood cell count decreased

15%

Diarrhoea

15%

Pyrexia

15%

Constipation

15%

Dyspnoea

14%

Leukopenia

11%

Alopecia

10%

Hyperglycaemia

10%

Pneumonia

10%

Abdominal pain

10%

Cough

Weight decreased

Alanine aminotransferase increased

Aspartate aminotransferase increased

Stomatitis

Back pain

Vomiting

Anemia

Dizziness

Blood alkaline phosphatase increased

Non-cardiac chest pain

Lymphocyte count decreased

Abdominal pain upper

Blood lactate dehydrogenase increased

Hypotension

Hypokalaemia

Hypomagnesaemia

Headache

Arthralgia

Febrile neutropenia

Muscular weakness

Productive cough

Pain in extremity

Bronchitis

Musculoskeletal chest pain

Hypertension

Musculoskeletal pain

Neck pain

Myalgia

Confusional state

Anxiety

Upper respiratory tract infection

Small cell lung cancer

Pleural effusion

Chronic obstructive pulmonary disease

Haemoglobin decreased

Hyponatraemia

Pulmonary embolism

Hypocalcaemia

Dysphonia

Respiratory tract infection

Hypertriglyceridaemia

Febrile bone marrow aplasia

Diarrhea

Rash

Klebsiella sepsis

Blood creatinine increased

Dyskinesia

Hypoxia

Dehydration

Acute coronary syndrome

Cardiac failure

Ejection fraction decreased

Epistaxis

Pyelonephritis

Atrial flutter

Dry mouth

Acute kidney injury

Death

Acute myocardial infarction

Supraventricular tachycardia

Gastrooesophageal reflux disease

Neutropenic colitis

Herpes zoster

Pain

Hypercholesterolaemia

Leukocytosis

Troponin I increased

Chest pain

Pleuritic pain

Malignant pleural effusion

Metastases to central nervous system

100%

80%

60%

40%

20%

Study treatment Arm

Part 2: Topotecan

Part 2: Dinutuximab + Irinotecan

Part 1: Dinutuximab + Irinotecan

Part 2: Irinotecan

Awards & Highlights

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Trabectedin and IrinotecanExperimental Treatment4 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Irinotecan

FDA approved

tumor biopsy

2018

Completed Phase 2

~120

0 / 9Eligibility criteria met