Lurbinectedin +/- Irinotecan for Small Cell Lung Cancer

Recruiting in Palo Alto (17 mi)

+237 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: PharmaMar

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Multicenter, open-label, randomized, controlled phase III clinical trial to evaluate and compare the activity and safety of two experimental arms consisting of lurbinectedin as single agent (Group A) or the combination of lurbinectedin with irinotecan (Group B) versus Investigator's Choice (topotecan or irinotecan) as control arm (Group C), in Small-cell Lung Cancer (SCLC) patients who failed one prior platinum-containing line.

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

The trial protocol does not specify if you need to stop your current medications. However, you must have at least three weeks since your last antineoplastic treatment and recover from any adverse events to grade ≤ 1. It's best to discuss your current medications with the trial team.

What data supports the idea that Lurbinectedin +/- Irinotecan for Small Cell Lung Cancer is an effective drug?

The available research shows that Irinotecan, when combined with another drug called cisplatin, significantly improved the survival of patients with extensive small-cell lung cancer compared to the standard treatment. Specifically, patients lived longer without the cancer getting worse, with a median time of 6.9 months compared to 4.8 months for the standard treatment. This suggests that Irinotecan, especially when used in combination with other drugs, can be an effective option for treating small-cell lung cancer.

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What safety data exists for Lurbinectedin and Irinotecan in treating small cell lung cancer?

Irinotecan (also known as CPT-11 or Camptosar) has been studied extensively in small cell lung cancer (SCLC) and other cancers. It has shown significant activity and is often used in combination with other drugs like cisplatin and etoposide. Studies have demonstrated its effectiveness and tolerability, with some trials indicating improved survival rates when combined with cisplatin. Lurbinectedin, approved for metastatic SCLC, has an acceptable and manageable safety profile at the approved dose of 3.2 mg/m2 every 3 weeks, as shown in a phase II basket trial involving 105 adult SCLC patients. Overall, both drugs have been evaluated for safety and efficacy in SCLC, with manageable side effects when used at recommended doses.

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Is the drug Irinotecan a promising treatment for small cell lung cancer?

Yes, Irinotecan is a promising drug for small cell lung cancer. Studies show it can improve survival when combined with other drugs like cisplatin, and it has shown significant antitumor activity. It is considered a valuable addition to treatment options for this type of cancer.

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Eligibility Criteria

Adults with small-cell lung cancer who've had one prior platinum-based chemotherapy can join this trial. They must have good organ function, no recent serious heart issues or uncontrolled infections, and cannot be pregnant or breastfeeding. Participants need to agree to use effective contraception and should not have been treated with certain drugs like lurbinectedin before.

Inclusion Criteria

Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN

Albumin ≥ 3.0 g/dL

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN)

Exclusion Criteria

I haven't had serious heart issues like a heart attack or unstable angina in the past year.

I have a heart rhythm problem that needs treatment.

I have a chronic liver condition that needs treatment and haven't taken hepatitis antiviral drugs in the last 6 months.

Participant Groups

The LAGOON trial is testing the effectiveness of Lurbinectedin alone (Group A) or combined with Irinotecan (Group B), compared to the standard treatment choice of Topotecan or Irinotecan (Group C). This phase III study randomly assigns patients to these groups in an open-label setting.

Group I: Lurbinectedin plus Irinotecan Experimental Treatment 2 Interventions

Patients will consecutively receive the following q3wk (every three weeks = one treatment cycle): * Irinotecan (Day 1 and Day 8) * Lurbinectedin (Day 1)

Group II: Lurbinectedin Experimental Treatment 1 Intervention

Patients will consecutively receive lurbinectedin on Day 1 q3wk (every three weeks = one treatment cycle)

Group III: Control arm Active Control 2 Interventions

Best Investigator's choice prior to randomization between: * Irinotecan on Day 1 q3wk * Topotecan on Days 1-5 q3wk

Irinotecan is already approved in United States, European Union, Japan, Canada for the following indications:

🇺🇸 Approved in United States as Camptosar for:

• Colorectal cancer

🇪🇺 Approved in European Union as Irinotecan for:

• Colorectal cancer

🇯🇵 Approved in Japan as Topotecin for:

• Colorectal cancer
• Small cell lung cancer

🇨🇦 Approved in Canada as Irinotecan for:

• Colorectal cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Florida Cancer Specialists West Palm Beach, FL

Duly Health and Care Joliet, IL

Hamilton Health Sciences -Juravinski Cancer Centre Hamilton, Canada

Southlake Regional Health Centre Newmarket, Canada

More Trial Locations

Who Is Running the Clinical Trial?

PharmaMar Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Irinotecan plus cisplatin in small-cell lung cancer. [2018] The DNA topoisomerase inhibitor irinotecan (CPT-11, Camptosar) is being evaluated as a novel chemotherapeutic agent for small-cell lung cancer that may complement other agents and treatment modalities. Combination chemotherapy is recognized as the most effective means of improving survival in patients with extensive-stage small-cell lung cancer, but until recently, no one combination had emerged as superior. In a recent Japanese phase III study, irinotecan in combination with cisplatin significantly improved survival of previously untreated patients with extensive small-cell lung cancer compared with standard etoposide/cisplatin therapy (median progression-free survival: 6.9 vs 4.8 months, P

2. United States pubmed.ncbi.nlm.nih.gov

Current status of irinotecan in lung cancer. [2018] Survival in lung cancer patients has not improved over the past 2 decades. Irinotecan (Camptosar, CPT-11), a semisynthetic analog of the quinoline-based alkaloid camptothecin, is one of several new drugs that have demonstrated promising activity in the treatment of lung cancer in recent years. This article gives a brief overview of the mechanism, development history, and current uses of this agent.

3. United States pubmed.ncbi.nlm.nih.gov

Dose-dense therapy with a novel irinotecan regimen for small-cell lung cancer. [2018] Irinotecan (CPT-11, Camptosar) has significant activity in small-cell lung cancer. In addition, preclinical models have demonstrated synergy between irinotecan and two standard front-line drugs for small-cell lung cancer: cisplatin and etoposide; phase III data also show significant survival benefit for irinotecan/cisplatin compared to standard treatment. These data suggest a potential clinical advantage to combining etoposide, cisplatin, and irinotecan as first-line therapy for small-cell lung cancer. The purpose of this phase I study was to establish if alternating weekly therapy with irinotecan/cisplatin and etoposide/cisplatin was tolerated and to determine the maximum tolerated dose of these agents in patients with small-cell lung cancer. Patients generally tolerated the weekly alternating chemotherapy with irinotecan/cisplatin and etoposide/cisplatin well, and this combination possessed significant antitumor activity in small-cell lung cancer.

4. England pubmed.ncbi.nlm.nih.gov

A randomised phase 2b study comparing the efficacy and safety of belotecan vs. topotecan as monotherapy for sensitive-relapsed small-cell lung cancer. [2021] This study compared the efficacy/safety of the camptothecin analogues belotecan and topotecan for sensitive-relapsed small-cell lung cancer (SCLC).

5. United States pubmed.ncbi.nlm.nih.gov

Combination of irinotecan and etoposide for treatment of refractory or relapsed small-cell lung cancer. [2018] To determine the response rate, survival, and toxicity of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, in refractory or relapsed small-cell lung cancer (SCLC).

6. England pubmed.ncbi.nlm.nih.gov

Phase I study of a weekly infusion of irinotecan hydrochloride (CPT-11) and a 14-day continuous infusion of etoposide in patients with lung cancer: JCOG trial 9408. [2019] The aim was to determine the maximum tolerated dose (MTD) and recommended dose of irinotecan hydrochloride (CPT-11) in combination with a 14-day continuous infusion of etoposide in patients with refractory advanced lung cancer (LC), especially small cell lung cancer (SCLC).

7. England pubmed.ncbi.nlm.nih.gov

Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours. [2023] Label="BACKGROUND">Lurbinectedin was approved by FDA and other health regulatory agencies for treating adults with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Safety profile at approved dose (3.2 mg/m2 every 3 weeks) was acceptable and manageable in 105 adult SCLC patients from a phase II basket trial. This study analyses safety data from several solid tumours treated at the lurbinectedin-approved dose.

8. United States pubmed.ncbi.nlm.nih.gov

Irinotecan in lymphoma, leukemia, and breast, pancreatic, ovarian, and small-cell lung cancers. [2018] Irincotecan (CPT-11 [Camptosar] has a board range of antitumor activity. Extensive preclinical and early clinical work has demonstrated its activity against many tumor types--head and neck, esophagus, stomach, pancreas, liver, colon/rectum, kidney, lymph nodes, ovary, uterine, cervix, sarcoma, melanoma, acute and chronic leukemia, mesothelioma, and cancers of unknown primary site. Most of the phase II and III trials have focused on colorectal and other gastrointestinal, non-small-cell lung, and cervical cancers (discussed elsewhere in this monograph). This article presents preliminary results of studies exploring the use of irinotecan in lymphoma, leukemia, and breast, pancreatic, ovarian, and small-cell lung cancers. In all of these studies, the number of patients enrolled is small, drug doses and schedules differ (often within the same case series), and little information is available on response duration and overall survival. Nevertheless, irinotecan has shown reproducible if at times modest activity in almost all of the diseases in which it has been studied. Future research should be directed at conducting well-designed clinical trials of irinotecan alone and in combination with other agents.