Lurbinectedin +/- Irinotecan for Small Cell Lung Cancer

Recruiting at 237 trial locations

Overseen By Mónica Insa

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: PharmaMar

Must not be taking: Topoisomerase inhibitors

Disqualifiers: CNS metastases, Heart disease, Liver disease, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 3

Duration: 39 months

705 Participants Needed

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have at least three weeks since your last cancer treatment and recover from any side effects before starting the trial.

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. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Lurbinectedin +/- Irinotecan for Small Cell Lung Cancer?

Research shows that Irinotecan, when combined with other drugs like cisplatin, significantly improves survival in patients with extensive-stage small-cell lung cancer compared to standard treatments. This suggests that Irinotecan has promising activity in treating this type of cancer. ^{1 2 3 4 5}

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. ^{1 3 6 7 8}

Is the combination of Lurbinectedin and Irinotecan safe for treating small cell lung cancer?

Lurbinectedin has been approved for treating small cell lung cancer and was found to have an acceptable and manageable safety profile in patients. Irinotecan, when used in combination with other drugs like cisplatin, has been generally well-tolerated in patients with small cell lung cancer, showing significant antitumor activity. ^{1 3 6 7 8}

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. ^{1 2 3 6 8}

What makes the drug Lurbinectedin +/- Irinotecan unique for small cell lung cancer?

Lurbinectedin combined with Irinotecan is unique because it explores a novel combination of drugs that may offer a new approach to treating small cell lung cancer, potentially improving outcomes compared to standard treatments. Irinotecan has shown significant activity in small cell lung cancer and has been effective in combination with other drugs, suggesting that this new combination could provide additional benefits. ^{1 2 3 6 8}

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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either lurbinectedin as a single agent, lurbinectedin in combination with irinotecan, or investigator's choice of topotecan or irinotecan

39 months

Every 3 weeks (q3wk) for treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• Irinotecan
• Lurbinectedin
• Topotecan

Trial Overview 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.

Participant Groups

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

Who Is Running the Clinical Trial?

PharmaMar

Lead Sponsor

Trials

93

Recruited

11,800+

José María Fernández de Sousa-Faro

PharmaMar

Chief Executive Officer since 1986

PhD in Biochemistry, Complutense University of Madrid

Carmen Cuevas Marchante

PharmaMar

Chief Medical Officer since 2002

MD, University of Navarra

Findings from Research

Irinotecan, when combined with cisplatin, significantly improves survival rates in previously untreated patients with extensive-stage small-cell lung cancer, showing a median progression-free survival of 6.9 months compared to 4.8 months with standard treatment (etoposide/cisplatin).

The combination therapy also resulted in a median overall survival of 12.8 months versus 9.4 months for the standard treatment, indicating that irinotecan could be a promising new option for enhancing treatment outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan plus cisplatin in small-cell lung cancer. Sandler, A.[2018]

Irinotecan, a semisynthetic version of camptothecin, has shown promising activity in treating lung cancer, which has seen stagnant survival rates over the past 20 years.

The article reviews the mechanism of action and development history of irinotecan, highlighting its potential as a new treatment option for lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of irinotecan in lung cancer. Fukuoka, M.[2018]

A phase I study found that alternating weekly therapy with irinotecan/cisplatin and etoposide/cisplatin was well-tolerated by patients with small-cell lung cancer, indicating a favorable safety profile for this treatment regimen.

The combination of these drugs demonstrated significant antitumor activity, suggesting a potential clinical advantage for using this approach as a first-line therapy in small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-dense therapy with a novel irinotecan regimen for small-cell lung cancer. Johnson, FM., Kurie, JM., Peeples, BO., et al.[2018]

Belotecan showed a higher objective response rate (33%) compared to topotecan (21%) and a significantly longer median overall survival (13.2 months vs. 8.2 months), suggesting it may be a more effective treatment for sensitive-relapsed small-cell lung cancer (SCLC).

Patients receiving belotecan also had a higher completion rate of treatment cycles (53% vs. 35%), indicating better tolerability and potential for improved patient adherence compared to topotecan.

NCBI (Pubmed)

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. Kang, JH., Lee, KH., Kim, DW., et al.[2021]

In a study of 25 patients with refractory or relapsed small-cell lung cancer (SCLC), the combination of irinotecan (CPT-11) and etoposide resulted in a high overall response rate of 71%, with 14 partial responses and 3 complete responses, indicating its potential efficacy as a treatment option.

The treatment was associated with significant toxicities, including severe myelosuppression (56% experienced grade 3 to 4 neutropenia), highlighting the need for careful monitoring and management of side effects, but it still shows promise for further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of irinotecan and etoposide for treatment of refractory or relapsed small-cell lung cancer. Masuda, N., Matsui, K., Negoro, S., et al.[2018]

The maximum tolerated dose (MTD) of irinotecan hydrochloride (CPT-11) in combination with etoposide for patients with refractory advanced lung cancer was determined to be 40 mg/m2, but this regimen was associated with significant toxicity, including one treatment-related death due to pulmonary toxicity.

Out of the nine patients studied, only two achieved a partial response, indicating that while there may be some therapeutic efficacy, the treatment's safety profile raises concerns, particularly regarding pulmonary complications in patients with a history of cytotoxic treatment.

NCBI (Pubmed)

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. Fujishiro, M., Shinkai, T., Fukuda, M., et al.[2019]

Lurbinectedin has a manageable safety profile when used at the approved dose of 3.2 mg/m2 every 3 weeks, as shown in a pooled analysis of 554 patients with various advanced solid tumors, including small cell lung cancer and ovarian cancer.

The most common side effects were transient hematological abnormalities, particularly neutropenia (41%) and leukopenia (30%), along with non-hematological issues like fatigue (63%) and nausea (57%), indicating that while side effects are present, they are generally manageable for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours. Leary, A., Oaknin, A., Trigo, JM., et al.[2023]

Irinotecan (CPT-11) has demonstrated a broad range of antitumor activity across various cancer types, including lymphoma, leukemia, and several solid tumors, although most studies have focused on colorectal and gastrointestinal cancers.

Preliminary results indicate that irinotecan shows modest but reproducible activity in multiple cancers, suggesting the need for further well-designed clinical trials to better understand its efficacy and optimal use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in lymphoma, leukemia, and breast, pancreatic, ovarian, and small-cell lung cancers. Rosen, LS.[2018]

References

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

Irinotecan plus cisplatin in small-cell lung cancer. [2018]

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

Current status of irinotecan in lung cancer. [2018]

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

Dose-dense therapy with a novel irinotecan regimen for small-cell lung cancer. [2018]

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]

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

Combination of irinotecan and etoposide for treatment of refractory or relapsed small-cell lung cancer. [2018]

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]

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

Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours. [2023]

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

Irinotecan in lymphoma, leukemia, and breast, pancreatic, ovarian, and small-cell lung cancers. [2018]