Lurbinectedin for Pancreatic Cancer

Overseen By Erkut Borazanci, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: HonorHealth Research Institute

Disqualifiers: Brain metastases, Cardiac disease, Immunocompromised, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test lurbinectedin, administered through an IV, for its effectiveness and safety in treating advanced gastrointestinal cancers. The focus is on patients with specific genetic mutations affecting DNA repair. This trial suits those who have not succeeded with previous treatments and have a type of gastrointestinal cancer that cannot be surgically removed or has spread. Participants should have these specific DNA mutations and have experienced progression after prior treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial requires a 'washout period' (time without taking certain medications) of at least three weeks since the last chemotherapy or investigational drugs before starting the study. It does not specify other medications, so you should discuss your current medications with the trial team.

Is there any evidence suggesting that lurbinectedin is likely to be safe for humans?

Research has shown that lurbinectedin has a good safety record across various studies. For instance, in real-world use, patients with advanced small cell lung cancer tolerated lurbinectedin well, experiencing modest benefits and manageable side effects. Early safety data from past studies indicated that administering lurbinectedin at a specific dose (3.2 mg/m2) resulted in fewer severe side effects.

Additionally, the FDA has granted fast-track approval to lurbinectedin for treating small cell lung cancer, indicating its safety for that condition. While this does not guarantee the same safety for pancreatic cancer, it offers some reassurance about its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pancreatic cancer, which often include chemotherapy drugs like gemcitabine and nab-paclitaxel, Lurbinectedin stands out with its unique mechanism of action. It is a novel compound that interacts with the DNA of cancer cells, inhibiting their ability to replicate and spread. Researchers are excited about Lurbinectedin because it targets the transcription process of cancer cells, potentially offering a new way to slow down or stop tumor growth. This could provide a fresh hope for patients, especially those who have not responded well to existing therapies.

What evidence suggests that lurbinectedin might be an effective treatment for pancreatic cancer?

Research has shown that lurbinectedin, the treatment under study in this trial, can kill pancreatic cancer cells in the lab. It proved effective as a single treatment against certain human pancreatic tumor cells. In real-world use, lurbinectedin has been safe and somewhat effective in treating other cancers, such as small cell lung cancer. Although more research is needed for pancreatic cancer, these early results are encouraging. The drug's ability to target cancer cells offers hope for patients with advanced gastrointestinal cancers. ^{2 4 6 7 8}

Who Is on the Research Team?

Erkut Borazanci, MD

Principal Investigator

HonorHealth Research Institute

Are You a Good Fit for This Trial?

Adults with advanced pancreatic cancer and specific DNA repair mutations who have had up to three prior chemotherapy treatments can join. They must have a measurable tumor, adequate organ function, and an ECOG performance status of ≤1. Pregnant or breastfeeding women, those with more than three chemo treatments, brain metastases, severe heart conditions, or active infections cannot participate.

Inclusion Criteria

My cancer in the digestive system has been confirmed by lab tests.

I am not able to bear children or agree to use effective birth control during and after the trial.

I can carry out all my self-care but cannot do heavy physical work.

Exclusion Criteria

My cancer has spread to my brain or the lining around my brain.

My cancer is of the neuroendocrine subtype.

History of cardiac disease, generalized edema, and/or ascites clinically evident or requiring drainages within three weeks prior to study entry, immunocompromised patients, known chronically active hepatitis B virus (HBV) or hepatitis C virus (HCV), 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, pregnant or breastfeeding women, live vaccine administration within 3 weeks of study entry

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Lurbinectedin is administered intravenously as a 1-hour infusion on Day 1 of each 3-week cycle, up to 12 cycles

36 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including overall survival and progression-free survival

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Lurbinectedin

Trial Overview The trial is testing the effectiveness and safety of Lurbinectedin (Zepzelca), a drug given through injection for treating advanced pancreatic cancer in patients with certain DNA repair mutations. The goal is to see how well it works on tumors that haven't responded well to previous treatments.

How Is the Trial Designed?

Group I: Lurbinectedin Experimental Treatment 1 Intervention

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).

Lurbinectedin is already approved in United States, European Union for the following indications:

Approved in United States as Zepzelca for:

• Metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy

Approved in European Union as Zepzelca for:

• Metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy

Who Is Running the Clinical Trial?

HonorHealth Research Institute

Lead Sponsor

Trials

26

Recruited

940+

Jazz Pharmaceuticals

Industry Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

The combination of lutetium-177 (177Lu)-octreotate with capecitabine and temozolomide was well tolerated in a phase I-II trial involving 35 patients with advanced low-grade neuroendocrine tumors, with no severe toxicities observed and only mild to moderate adverse effects reported.

The treatment demonstrated significant efficacy, achieving a complete response in 15% and a partial response in 38% of patients, with a median progression-free survival of 31 months, indicating strong tumor control rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I-II study of radiopeptide 177Lu-octreotate in combination with capecitabine and temozolomide in advanced low-grade neuroendocrine tumors. Claringbold, PG., Price, RA., Turner, JH.[2022]

Peptide receptor chemoradionuclide therapy (PRCRT) using (177)Lu-octreotate combined with 5FU chemotherapy showed promising results in five patients with inoperable pancreatic and duodenal neuroendocrine tumors, with all patients exhibiting a scintigraphic response and four showing a radiological response after three months.

The treatment not only provided ongoing responses beyond three months but also allowed for curative surgery in one patient, suggesting that PRCRT may serve as an effective neoadjuvant therapy for these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential for induction peptide receptor chemoradionuclide therapy to render inoperable pancreatic and duodenal neuroendocrine tumours resectable. Barber, TW., Hofman, MS., Thomson, BN., et al.[2022]

In a study involving seven patients, the combination of (177)Lu-octreotate and capecitabine showed a manageable short-term toxicity profile, with no severe side effects like grade 3 or 4 leukopenia or neutropenia, and no significant renal impairment.

The treatment was deemed feasible and safe, prompting the initiation of a randomized controlled trial to further evaluate its anti-tumor efficacy compared to (177)Lu-octreotate alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Report on short-term side effects of treatments with 177Lu-octreotate in combination with capecitabine in seven patients with gastroenteropancreatic neuroendocrine tumours. van Essen, M., Krenning, EP., Kam, BL., et al.[2022]

Lutetium peptide receptor radionuclide therapy (Lu-PRRT) is an effective second-line treatment for progressive, metastatic well-differentiated neuroendocrine tumors (WD-NETs), with a median progression-free survival of 38 months observed in a study of 45 patients.

While 51% of patients experienced a partial response to Lu-PRRT, there were serious side effects, including two cases of leukemia, highlighting the need for further research on the impact of prior treatments on Lu-PRRT outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world efficacy of lutetium peptide receptor radionuclide therapy in patients with neuroendocrine tumours. Almeamar, H., Cullen, L., Murphy, DJ., et al.[2022]

Two novel patient-derived cell lines from pancreatic ductal adenocarcinoma (PDAC) tumors, LuPanc-1 and LuPanc-2, exhibit distinct molecular characteristics and responses to treatment, highlighting the importance of individual tumor biology in therapy selection.

LuPanc-1 cells showed greater sensitivity to gemcitabine and FOLFIRINOX compared to LuPanc-2, suggesting that these cell lines can be used to explore personalized treatment strategies for PDAC based on their unique genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment and Molecular Characterization of Two Patient-Derived Pancreatic Ductal Adenocarcinoma Cell Lines as Preclinical Models for Treatment Response. Braun, R., Lapshyna, O., Watzelt, J., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37999116/

Preclinical Synergistic Combination Therapy of ... We now demonstrate lurbinectedin's highly efficient killing of human-derived pancreatic tumor cell lines PANC-1, BxPC-3, and HPAF-II as a single agent.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10670398/

Preclinical Synergistic Combination Therapy of ... Overall, our results indicate that lurbinectedin is an efficient killer of human-derived pancreatic cancer cell lines as a single agent and in combination with ...

3. cancernetwork.com cancernetwork.com/view/real-world-lurbinectedin-exhibits-safety-and-modest-efficacy-in-es-sclc

Real-World Lurbinectedin Exhibits Safety and Modest ... Lurbinectedin (Zepzelca) displayed a favorable safety profile and modest efficacy outcomes as a therapy with compassionate use in patients with extensive-stage ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02210364?term=AREA%5BBasicSearch%5D(PM-1183)&rank=4

Study of Lurbinectedin (PM01183) in Combination With ... Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of Lurbinectedin (PM01183) in Combination with Capecitabine in Patients with ...

5. onclive.com onclive.com/view/lurbinectedin-plus-irinotecan-is-safe-prolongs-responses-in-high-risk-pretreated-sclc

Lurbinectedin Plus Irinotecan Is Safe, Prolongs Responses ... Lurbinectedin and irinotecan combination achieved a 43.6% overall response rate in high-risk SCLC patients. · Median duration of response was 7.1 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07121478

Patients With High-grade Pancreatic Neuroendocrine Tumors Lurbinectedin, a selective inhibitor of oncogenic transcription, recently received accelerated FDA approval for lung cancer (small cell type) after ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05229588

Study Details | NCT05229588 | Lurbinectedin in Patients ... The purpose of this research is to evaluate the activity and safety of lurbinectedin in adult patients with advanced Gastrointestinal Malignancies with DNA ...

8. fda.gov fda.gov/media/105933/download

PM01183 preliminary safety data from phase 2 studies has suggested that lurbinectedin given at 3.2 mg/m2 results in a lower incidence of grade 3/4 ...