Lurbinectedin in Patients With Advanced Gastrointestinal Malignancies With DNA Repair Mutations

NCT05229588 | Completed Phase 2 FDA Drug

• 1 other identifier: HRI-Lurbinectedin-001
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research is to evaluate the activity and safety of lurbinectedin in adult patients with advanced Gastrointestinal Malignancies with DNA repair mutations.

Conditions

Gastrointestinal Malignancies

Keywords

Gastrointestinal Malignancies; phase II

Outcome Measures

Primary Outcomes (1)

• Evaluate the antitumor activity

  To evaluate the antitumor activity of Lurbinectedin in terms of overall response rate (ORR), according to RECIST v.1.1, in patients with advanced pancreatic cancer with DNA repair mutations.

  Initiation of study treatment up to 10 cycles (each cycle is 21 days ± 48 hours)

Secondary Outcomes (9)

• Duration of response (DOR)

  Initiation of study treatment up to study completion, up to 2 years

• Clinical benefit

  Initiation of study treatment up to study completion, up to 2 years

• Measure amount of CA19-9, CEA, or CA125

  Initiation of study treatment up to 12 cycles (each cycle is 21 days ± 48 hours)

• Progression-free survival (PFS)

  Initiation of study treatment up to 12 cycles (each cycle is 21 days ± 48 hours)

• Progression-free survival rate at three months (PFS3)

  Initiation of study treatment up to three months after the first infusion

Study Arms (1)

Lurbinectedin

EXPERIMENTAL

Lurbinectedin will be administered intravenously (IV) as a 1-hour (±10 min) infusion on Day 1 of each cycle (one cycle = 3 weeks ± 48 hours).

Drug: Lurbinectedin 4 MG Injection [Zepzelca]

Interventions

Lurbinectedin 4 MG Injection [Zepzelca] DRUG

Lurbinectedin will be administered with a minimum total volume of 100 mL of solution for infusion (either on 5% glucose or 0.9% sodium chloride). Lurbinectedin will be administered intravenously through peripheral or central lines at a dose of 3.2 mg/m2 at a fixed infusion rate.

Also known as: PM01183

Lurbinectedin

Eligibility Criteria

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

You may qualify if:

• Voluntary written informed consent form (ICF) of the patient obtained before any study-specific procedure.
• Age ≥ 18 years of age; male or female.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≤1
• Histologically or cytologically confirmed gastrointestinal carcinoma
• Locally advanced unresectable or metastatic disease at study entry
• Known deleterious or suspected deleterious (or equivalent interpretation) mutations in DNA repair in ATM, ATR, CHEK2, BRCA1, BRCA2, RAD51, BRIP1, PALB2, PTEN, FANC, NBN, EMSY, MRE11, or ARID1A prior to study entry
• Progressive disease to prior treatment. Patients no longer able to continue prior treatment due to intolerable toxicity may be considered for study participation provided that radiology assessment confirms either stable disease or disease progression (i.e., no response to treatment).
• Measurable tumor lesions according to RECIST 1.1 criteria.
• Adequate hematological, renal, metabolic and hepatic function, defined as:
• Hemoglobin ≥9 g/dL (patients may have received prior red blood cell \[RBC\] transfusion, if clinically indicated); absolute neutrophil count (ANC) ≥1.5 x 109/L, and platelet count ≥100 x 109/L.
• Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3.0 x upper limit of normal (ULN).
• Total bilirubin ≤ ULN.
• Albumin ≥3.0 g/dL.
• Calculated creatinine clearance (CrCL) ≥30 mL/min (according to the Cockcroft and Gault´s formula).
• \. Washout periods prior to Day 1 of Cycle 1:

You may not qualify if:

• Prior treatment with lurbinectedin or trabectedin
• Neuroendocrine differentiation subtype in histology
• More than three prior systemic chemotherapy lines for advanced disease
• Known brain metastases or leptomeningeal disease involvement
• Concomitant diseases/conditions:
• History of cardiac disease: myocardial infarction or symptomatic/uncontrolled angina within the year prior to enrollment; or pain history of left ventricular ejection fraction (LVEF) ≤ 50% assessed by multiple-gated acquisition scan (MUGA) or equivalent by ultrasound (US); or symptomatic arrhythmia.
• Generalized edema, and/or ascites clinically evident or requiring drainages within three weeks prior to study entry. Permanent external drainages due to ascites are also excluded.
• Immunocompromised patients, including those known to be infected by human immunodeficiency virus (HIV).
• Known chronically active hepatitis B virus (HBV) or hepatitis C virus (HCV). For hepatitis B, this includes positive tests for both hepatitis B surface antigen and quantitative hepatitis B polymerase chain reaction (PCR). For hepatitis C, this includes positive tests for both hepatitis C antibody and quantitative hepatitis C PCR.
• Active uncontrolled infection.
• Limitation of the patient's ability to comply with the treatment or to follow-up the protocol.
• Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
• Patients acutely ill and/or in immediate vital distress, including those with rapidly deteriorating clinical condition or who may require unscheduled hospitalizations due to uncontrolled disease symptoms within the prior two weeks to treatment registration.
• Pregnant or breastfeeding women.
• Live vaccine administration within 3 weeks of study entry

Sponsors & Collaborators

• HonorHealth Research Institute: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (1)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

MeSH Terms

Interventions

PM 01183; Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Erkut Borazanci, MD

  HonorHealth Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2022
• First Posted: February 8, 2022
• Study Start: June 14, 2022
• Primary Completion: August 4, 2025
• Study Completion: August 4, 2025
• Last Updated: August 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)