search
Back to results

Lurbinectedin in Patients With Advanced Pancreatic Cancer With DNA Repair Mutations

Primary Purpose

Pancreas Cancer

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Lurbinectedin 4 MG Injection [Zepzelca]
Sponsored by
HonorHealth Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreas Cancer focused on measuring pancreatic cancer, phase II

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 cancer of the exocrine pancreas
  • 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
  • Up to three prior systemic chemotherapy lines for advanced disease.
  • 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
  • Prior treatment with poly (ADP-ribose) polymerase (PARP) inhibitors
  • Neuroendocrine differentiation or mucinous 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

Sites / Locations

  • HonorHealth Research InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lurbinectedin

Arm Description

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Duration of response (DOR)
Duration of response (DOR), defined as the time from the date when the response criteria (PR or CR) are fulfilled to the date of PD, recurrence or death.
Clinical benefit
Clinical benefit, defined as the percentage of patients with ORR or SD ≥4 months, according to RECIST v.1.1.
Measure amount of CA19-9, CEA, or CA125
Measure amount of CA19-9, CEA, or CA125 (whichever is being followed) in blood during treatment.
Progression-free survival (PFS)
Progression-free survival (PFS), defined as the time from the date of first infusion to the date of PD, death (of any cause), or last tumor evaluation.
Progression-free survival rate at three months (PFS3)
Progression-free survival rate at three months (PFS3), defined as the percentage of patients who are alive and progression-free three months after the first infusion.
Overall survival (OS)
Overall survival (OS), defined as the time from the date of first infusion to the date of death (of any cause) or last patient contact.
Overall survival rate at six months (OS6)
Overall survival rate at six months (OS6), defined as the percentage of patients who were alive six months after the first infusion
Overall survival rate at 12 months (OS12)
Overall survival rate at 12 months (OS12), defined as the percentage of patients who were alive 12 months after the first infusion
Treatment safety
Treatment safety: AEs, serious AEs (SAEs) and laboratory abnormalities graded according to the NCI-CTCAE v.5

Full Information

First Posted
January 5, 2022
Last Updated
September 14, 2023
Sponsor
HonorHealth Research Institute
Collaborators
Jazz Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT05229588
Brief Title
Lurbinectedin in Patients With Advanced Pancreatic Cancer With DNA Repair Mutations
Official Title
A Phase II Pilot Clinical Trial of Lurbinectedin (Zepzelca™ PM01183) in Patients With Advanced Pancreatic Cancer With DNA Repair Mutations
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 14, 2022 (Actual)
Primary Completion Date
August 31, 2025 (Anticipated)
Study Completion Date
August 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HonorHealth Research Institute
Collaborators
Jazz Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this research is to evaluate the activity and safety of lurbinectedin in adult patients with advanced pancreatic cancer with DNA repair mutations.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreas Cancer
Keywords
pancreatic cancer, phase II

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Lurbinectedin
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Lurbinectedin 4 MG Injection [Zepzelca]
Other Intervention Name(s)
PM01183
Intervention Description
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.
Primary Outcome Measure Information:
Title
Evaluate the antitumor activity
Description
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.
Time Frame
Initiation of study treatment up to 10 cycles (each cycle is 21 days ± 48 hours)
Secondary Outcome Measure Information:
Title
Duration of response (DOR)
Description
Duration of response (DOR), defined as the time from the date when the response criteria (PR or CR) are fulfilled to the date of PD, recurrence or death.
Time Frame
Initiation of study treatment up to study completion, up to 2 years
Title
Clinical benefit
Description
Clinical benefit, defined as the percentage of patients with ORR or SD ≥4 months, according to RECIST v.1.1.
Time Frame
Initiation of study treatment up to study completion, up to 2 years
Title
Measure amount of CA19-9, CEA, or CA125
Description
Measure amount of CA19-9, CEA, or CA125 (whichever is being followed) in blood during treatment.
Time Frame
Initiation of study treatment up to 12 cycles (each cycle is 21 days ± 48 hours)
Title
Progression-free survival (PFS)
Description
Progression-free survival (PFS), defined as the time from the date of first infusion to the date of PD, death (of any cause), or last tumor evaluation.
Time Frame
Initiation of study treatment up to 12 cycles (each cycle is 21 days ± 48 hours)
Title
Progression-free survival rate at three months (PFS3)
Description
Progression-free survival rate at three months (PFS3), defined as the percentage of patients who are alive and progression-free three months after the first infusion.
Time Frame
Initiation of study treatment up to three months after the first infusion
Title
Overall survival (OS)
Description
Overall survival (OS), defined as the time from the date of first infusion to the date of death (of any cause) or last patient contact.
Time Frame
Initiation of study treatment up to 2 years
Title
Overall survival rate at six months (OS6)
Description
Overall survival rate at six months (OS6), defined as the percentage of patients who were alive six months after the first infusion
Time Frame
Initiation of study treatment up to six months after the first infusion
Title
Overall survival rate at 12 months (OS12)
Description
Overall survival rate at 12 months (OS12), defined as the percentage of patients who were alive 12 months after the first infusion
Time Frame
Initiation of study treatment up to 12 months after the first infusion
Title
Treatment safety
Description
Treatment safety: AEs, serious AEs (SAEs) and laboratory abnormalities graded according to the NCI-CTCAE v.5
Time Frame
Initiation of study treatment up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 cancer of the exocrine pancreas 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 Up to three prior systemic chemotherapy lines for advanced disease. 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). 11. Washout periods prior to Day 1 of Cycle 1: At least three weeks since last prior chemotherapy and/or investigational drugs. At least four weeks since the last radiotherapy (RT) > 30 Gy. 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 Prior treatment with poly (ADP-ribose) polymerase (PARP) inhibitors Neuroendocrine differentiation or mucinous 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Erkut Borazanci, MD
Phone
480-323-1364
Email
clinicaltrials@honorhealth.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Erkut Borazanci, MD
Organizational Affiliation
HonorHealth Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
HonorHealth Research Institute
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joyce Schaffer, RN, MSN, AOCNS
Phone
480-323-1364
Email
clinicaltrials@honorhealth.com
First Name & Middle Initial & Last Name & Degree
Andrea House
Phone
480-323-1364
Email
clinicaltrials@honorhealth.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Lurbinectedin in Patients With Advanced Pancreatic Cancer With DNA Repair Mutations

We'll reach out to this number within 24 hrs