Lurbinectedin With or Without Irinotecan in Treating Patients With Relapsed or High Risk Metastatic Ewing Sarcoma

NCT05042934 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 2017-0607NCI-2019-01258
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/II trial studies best dose and side effects of lurbinectedin and how well it works with or without irinotecan in treating patients with Ewing sarcoma that has come back (relapsed) or is high risk and has spread to other places in the body (metastatic). Lurbinectedin may decrease chemicals in the body related to Ewing sarcoma, and reducing these chemicals may make the tumor cells more sensitive to irinotecan. Chemotherapy drugs, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving lurbinectedin with or without irinotecan may work better in treating patients with Ewing sarcoma.

Conditions

Metastatic Ewing Sarcoma; Recurrent Ewing Sarcoma

Outcome Measures

Primary Outcomes (8)

• Time course of nuclear receptor subfamily 0 group B member 1 (NR0B1) suppression, Werner syndrome RecQ like helicase (WRN) suppression, and S-phase blockade (Phase IB)

  All analyses of data will be descriptive in nature.

  Up to 2 years

• NR0B1 suppression, and S-phase blockade after lurbinectedin (Phase IB)

  All analyses of data will be descriptive in nature.

  Up to 2 years

• Recommended dose of lurbinectedin (Phase IB)

  Dose-limiting toxicity is defined as grade 3 or 4 toxicity that does not resolve to grade 1 or less by 4 weeks.

  Up to 21 days

• Suppression extension of NR0B1 (Phase II)

  Up to 2 years

• Histological characteristics of patients (Phase II)

  Will assess the histological characteristics of patients to determine if they are true responders by descriptive statistics.

  Up to 2 years

• Progression-free survival (PFS) (Phase II)

  Will be estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in survival between groups. Regression analysis of survival data based on the Cox proportional hazards model will be conducted on PFS. The proportional hazards assumption will be evaluated graphically and analytically, and regression diagnostics (e.g., martingale and Shoenfeld residuals) will be examined to ensure that the models are appropriate.

  Time from treatment onset to either disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) or death from any cause, assessed up to 2 years

• Overall survival (OS) (Phase II)

  Will be estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in survival between groups. Regression analysis of survival data based on the Cox proportional hazards model will be conducted on OS. The proportional hazards assumption will be evaluated graphically and analytically, and regression diagnostics (e.g., martingale and Shoenfeld residuals) will be examined to ensure that the models are appropriate.

  Time from treatment onset to death, assessed up to 2 years

• Overall response rate (Phase II)

  Will be defined as evidence of complete or partial response 6 weeks after the initiation of combination therapy.

  At 6 weeks

Study Arms (1)

Treatment (lurbinectedin, fine-needle aspiration, irinotecan)

EXPERIMENTAL

Patients receive lurbinectedin IV over 60 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo fine-needle aspiration on days 2-6 of cycle 1. Beginning in cycle 2, if the biopsy shows suppression of NR0B1, then patients receive irinotecan IV over 1 hour on the day of maximum NR0B1 suppression on cycle 2. If the duration of NR0B1 suppression from lurbinectedin alone exceeds 48 hours, or if the duration of NR0B1 suppression from lurbinectedin and irinotecan exceeds 48 hours and is longer than that seen with lurbinectedin alone, then patients may receive a second dose of irinotecan during the extended period of NR0B1 suppression.

Procedure: Fine-Needle Aspiration; Drug: Irinotecan; Drug: Irinotecan Hydrochloride; Drug: Lurbinectedin

Interventions

Fine-Needle Aspiration PROCEDURE

Undergo fine-needle aspiration

Also known as: Aspirate, Fine Needle, Fine Needle Aspiration, Fine Needle Biopsy, fine-needle aspiration biopsy, FNA, FNA biopsy

Treatment (lurbinectedin, fine-needle aspiration, irinotecan)

Irinotecan DRUG

Given IV

Treatment (lurbinectedin, fine-needle aspiration, irinotecan)

Irinotecan Hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, Irinotecan Hydrochloride Trihydrate, Irinotecan Monohydrochloride Trihydrate, U-101440E

Treatment (lurbinectedin, fine-needle aspiration, irinotecan)

Lurbinectedin DRUG

Given IV

Also known as: PM01183, Zepzelca

Treatment (lurbinectedin, fine-needle aspiration, irinotecan)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase I: Patients of any age \>= 16 with documented Ewing sarcoma with disease accessible for repeated fine-needle aspiration biopsies who have relapsed after or are considered high-risk (unlikely to be cured by standard therapy) are eligible for the initial pharmacologic investigations. The previously untreated patients will be treated only with a single dose of lurbinectedin as if in a "window" protocol
• Patients must have a confirmed diagnosis of Ewing sarcoma, measurable evaluable disease, and have relapsed after standard chemotherapy or have high-risk metastatic disease unlikely to be cured with standard therapy (such as multiple bone metastases). a. Phase I: Patients must have documented Ewing sarcoma with disease accessible for repeated fine-needle aspiration biopsies. b. Phase II: Patients must have relapsed after initial curative or palliative therapy. Disease accessible for repeated biopsies is not required
• Phase II: Patients of any age \>= 16 with documented Ewing sarcoma who have relapsed after initial curative or palliative therapy are eligible. Disease accessible for repeated biopsies is not required
• Patients may have any translocation type, but a sufficient number of EWS-FLI1 patients to meet objectives 1, 3, and 4 is required for study completion
• Prior treatment with irinotecan is permitted
• Estimated life expectancy of greater than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Patients must be \>= 2 weeks beyond treatment of any chemotherapy, other investigational therapy, biological, targeted agents or radiotherapy, and must have recovered to =\< grade 1 toxicity or previous baseline for each toxicity
• Abnormal organ function is permitted
• Absolute neutrophil count \>= 1500/mL
• Platelets \>= 100,000/mL unless due to bone-marrow infiltration by tumor
• Creatinine =\< 1.5 x upper limit of normal (ULN) (or calculated glomerular filtration rate \[GFR\] \> 30 ml/min)
• Bilirubin =\< 1.6 mg/dL (1.5 x ULN) or direct bilirubin =\< 0.3 mg/dL
• Aspartate transaminase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and/or alanine transaminase (ALT)/serum glutamic-pyruvic transaminase (SGPT) =\< 2.5 x upper limit of normal (ULN)
• International normalized ratio (INR) =\< 2

You may not qualify if:

• Patients may not be receiving any other investigational agents
• Patients who are pregnant or breastfeeding
• Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 6 months after the end of treatment
• Patients with uncontrolled intercurrent illness including, but not limited to active infection requiring hospitalization
• Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus \[HBV\]-deoxyribonucleic acid \[DNA\] and/or positive hepatitis B virus surface antigen \[Hbs/Ag\], quantifiable hepatitis C virus \[HCV\]-ribonucleic acid \[RNA\])
• Active, bleeding diathesis
• Known history of human immunodeficiency virus (HIV) seropositivity
• Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study
• Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
• Prior treatment with PM01183, or trabectedin
• Evident symptomatic pulmonary fibrosis or interstitial pneumonitis, pleural or cardiac effusion rapidly increasing and/or necessitating prompt local treatment within seven days
• Known hypersensitivity to irinotecan

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Sarcoma, Ewing

Interventions

Biopsy, Fine-Needle; Irinotecan; PM 01183

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Biopsy, Needle; Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Punctures; Investigative Techniques; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Robert S Benjamin

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2021
• First Posted: September 13, 2021
• Study Start: September 15, 2021
• Primary Completion: August 30, 2022
• Study Completion: August 30, 2022
• Last Updated: February 10, 2022

Record last verified: 2022-02

Locations

US (1)