Overview

Lurbinectedin in Patients With Advanced Pancreatic Cancer With DNA Repair Mutations

Status:
Not yet recruiting
Trial end date:
2026-03-31
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
HonorHealth Research Institute
Collaborator:
Jazz Pharmaceuticals
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:

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