Lurbinectedin in Patients With Advanced Gastrointestinal Malignancies With DNA Repair Mutations

August 18, 2026 updated by: HonorHealth Research Institute

A Phase II Pilot Clinical Trial of Lurbinectedin (Zepzelca™ PM01183) in Patients With Gastrointestinal Malignancies With DNA Repair Mutations

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • HonorHealth Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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:

    1. 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.
    2. Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3.0 x upper limit of normal (ULN).
    3. Total bilirubin ≤ ULN.
    4. Albumin ≥3.0 g/dL.
    5. Calculated creatinine clearance (CrCL) ≥30 mL/min (according to the Cockcroft and Gault´s formula).

  • 11. Washout periods prior to Day 1 of Cycle 1:

    1. At least three weeks since last prior chemotherapy and/or investigational drugs.
    2. At least four weeks since the last radiotherapy (RT) > 30 Gy.
    3. At least two weeks since the last palliative RT (≤ 10 fractions or ≤ 30 Gy total dose).
  • Patients with prior malignancy successfully treated who are currently stable and on no active treatment are eligible.
  • Recovery to grade ≤1 from any adverse event (AE) derived from previous anticancer treatment (excluding alopecia and/or skin toxicity of any grade and grade ≤2 peripheral neuropathy) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, v.5).

  • Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure* during the trial and up to six weeks after treatment discontinuation, and fertile male patients with WOCBP partners must agree to refrain from fathering a child or donating sperm during the trial and up to four months after treatment discontinuation.

    • Highly effective methods: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; progestogen-only hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; sexual abstinence

Exclusion Criteria:

  • 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:

    1. 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.
    2. 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.
    3. Immunocompromised patients, including those known to be infected by human immunodeficiency virus (HIV).
    4. 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.
    5. Active uncontrolled infection.
    6. Limitation of the patient's ability to comply with the treatment or to follow-up the protocol.
    7. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Lurbinectedin
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]

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.

Other Names:
  • PM01183

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) at 12 Weeks
Time Frame: 12 weeks

The antitumor activity of lurbinectedin was measured in terms of overall response rate (ORR) at 12 weeks.

ORR was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) according to RECIST v.1.1. CR was defined as the complete radiologic disappearance of all target lesions, while PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions.
12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR)
Time Frame: From initiation of study treatment up to study completion, up to 20 months

Duration of response (DOR) was defined as the time from when a participant was reported to respond to lurbinectedin treatment (complete response (CR) or partial response (PR) by RECIST v1.1) to the time when they experienced progressive disease (PD) or death.

CR was defined as the complete radiologic disappearance of all target lesions, PR as at least a 30% decrease in the sum of the longest diameter of target lesions, and PD as at least a 20% increase in the sum of the longest diameter of target lesions.
From initiation of study treatment up to study completion, up to 20 months
Clinical Benefit
Time Frame: From 4 months up to 20 months

Clinical benefit was defined as the percentage of patients with a complete response (CR), partial response (PR), or stable disease (SD), as measured by RECIST v.1.1, for ≥4 months.

CR was defined as the complete radiologic disappearance of all target lesions, PR as at least a 30% decrease in the sum of the longest diameter of target lesions, and SD as no change in the sum of the longest diameter of target lesions.
From 4 months up to 20 months
Normalization of Tumor Markers
Time Frame: From initiation of study treatment until end of study treatment, up to 9.1 weeks

The number of participants with > 2 x ULN tumor marker values at baseline who had their tumor marker values normalize to at or below ULN after receiving lurbinectedin therapy.

Tumor markers included CA19-9 and CEA for non-expressors of CA 19-9. ULN was defined at 35 U/mL for CA 19-9 and 3 ng/mL for CEA.
From initiation of study treatment until end of study treatment, up to 9.1 weeks
Progression-free Survival (PFS)
Time Frame: From initiation of study treatment to disease progression/death/last tumor evaluation, up to 4.1 months
Progression-free survival (PFS) was defined as the time from the first infusion of lurbinectedin to the date of progressive disease, death (of any cause), or last tumor evaluation.
From initiation of study treatment to disease progression/death/last tumor evaluation, up to 4.1 months
Progression-free Survival Rate at Three Months (PFS3)
Time Frame: 3 months
Progression-free survival rate at three months (PFS3) was defined as the percentage of patients who were alive and progression-free three months after the first infusion of lurbinectedin.
3 months
Overall Survival (OS)
Time Frame: From initiation of study treatment to date of death/last patient contact, up to 20 months
Overall survival (OS) was defined as the time from the first infusion of lurbinectedin to the date of death (of any cause) or last patient contact.
From initiation of study treatment to date of death/last patient contact, up to 20 months
Overall Survival Rate at Six Months (OS6)
Time Frame: 6 months
Overall survival rate at six months (OS6) was defined as the percentage of patients who were alive six months after the first infusion of lurbinectedin.
6 months
Overall Survival Rate at 12 Months (OS12)
Time Frame: 12 months
Overall survival rate at 12 months (OS12) was defined as the percentage of patients who were alive 12 months after the first infusion of lurbinectedin.
12 months
Adverse Events Possibly or Definitely Related to Lurbinectedin
Time Frame: From initiation of study treatment to end of follow-up, up to 20 months

Adverse events (AEs) were graded and collected according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0). AEs that were determined to be possibly or definitely related to lurbinectedin are reported here.

The AE grading scale for NCI-CTCAE v5.0 is as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe, non-life threatening; Grade 4 - life-threatening; Grade 5 - death.
From initiation of study treatment to end of follow-up, up to 20 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
HonorHealth Research Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Jazz Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Erkut Borazanci, MD, HonorHealth Research Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 14, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 4, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 4, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 5, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 4, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 8, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 11, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 18, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HRI-Lurbinectedin-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings