Lurbinectedin + Irinotecan for Cancer

No longer recruiting at 25 trial locations

Overseen By Pharma Mar Clinical Oncology

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: PharmaMar

Must not be taking: Topoisomerase inhibitors

Disqualifiers: Heart disease, Uncontrolled infection, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, Lurbinectedin and Irinotecan (also known as Camptosar or CPT-11), to determine their effectiveness in treating various advanced cancers. It seeks to identify the right doses and assess the treatment's efficacy. The trial is open to individuals with specific types of advanced cancers, such as glioblastoma, soft-tissue sarcoma, and small cell lung cancer, who have undergone a certain number of previous treatments. Participants should have experienced disease progression after their last therapy and must meet other health criteria. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants a chance to contribute to groundbreaking cancer research.

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

The trial protocol does not specify if you need to stop taking your current medications. However, there is a requirement to wait at least three weeks after your last anticancer therapy before starting the trial, and certain exceptions apply for specific drugs. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown lurbinectedin to be safe. It was tested on patients with extensive-stage small cell lung cancer (ES-SCLC) and proved both safe and effective. Most patients tolerated it well, and any safety issues were manageable.

Safety checks for irinotecan have revealed some risks. Serious outcomes, such as hospitalizations and deaths, occurred in some cases. However, many patients experienced stable or improved health. Common side effects included a low white blood cell count and delayed diarrhea.

Since the current trial is in an early phase, researchers are still determining the right doses and safety of these drugs when used together. Early phase trials primarily focus on ensuring treatments are safe for people, so they closely monitor participants for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment combining Lurbinectedin and Irinotecan for cancer because it offers a potentially novel approach compared to existing options like chemotherapy and targeted therapies. Lurbinectedin is particularly intriguing as it targets transcription processes vital for cancer cell survival, which is different from the typical mechanisms of standard chemotherapies that primarily attack cell division. This combination also uses a specific dosing schedule to optimize the effectiveness of each drug, potentially enhancing their cancer-fighting capabilities while minimizing side effects. By exploring these unique mechanisms and administration strategies, researchers hope to improve treatment outcomes for patients with cancer.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that Lurbinectedin can help fight tumors, especially when combined with other treatments. This trial will administer different combinations of Lurbinectedin and Irinotecan to participants. In patients who received Lurbinectedin, 23.1% experienced a tumor response. Studies have found Irinotecan response rates between 14% and 22%. It has helped patients live longer and shrink tumors, even for those previously treated with chemotherapy. Both treatments show promise in fighting cancer, and using them together might enhance their effectiveness. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

Adults with certain advanced solid tumors who've had a break from cancer treatments for at least three weeks, are in fairly good health (ECOG ≤ 1), and have a life expectancy of over three months. They must not be pregnant or breastfeeding and should use effective contraception. Excluded are those with active COVID-19, prior significant bone marrow treatments, known brain metastases, or allergies to study drugs.

Inclusion Criteria

At least three weeks since the last anticancer therapy, (including immunotherapy, investigational drugs and radiotherapy), and at least six weeks since nitrosoureas and mitomycin C (systemic)

Voluntarily signed and dated written informed consent prior to any specific-study procedure

Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1

Exclusion Criteria

Active Coronavirus disease (COVID-19) (this includes positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal/oropharyngeal swabs or nasal swabs by PCR)

Prior bone marrow or stem cell transplantation, or radiation therapy in more than 35% of bone marrow

Women who are pregnant or breast feeding and fertile patients (men and women) who are not using an effective method of contraception

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Dose Escalation

Patients with selected advanced solid tumors are divided into three groups for dose escalation to determine the Maximum Tolerated Dose (MTD).

3 weeks per cycle

Multiple visits per cycle for dose administration and monitoring

Phase II Expansion

Tumor-specific expansion cohorts are treated at the Recommended Dose (RD) to evaluate efficacy in specific tumor types.

66 months

Regular visits for treatment and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months after the inclusion of the last evaluable patient

What Are the Treatments Tested in This Trial?

Interventions

• Irinotecan
• Lurbinectedin

Trial Overview

This is an early-phase trial testing the combination of two cancer drugs: Lurbinectedin and Irinotecan. It's divided into two parts: first finding the right doses (Phase I) and then expanding to more patients at that dose (Phase II).

How Is the Trial Designed?

Group I: Lurbinectedin Escalation Group Experimental Treatment 2 Interventions

Irinotecan 75 mg/m\^2 as a 90-min (-5-min/+30-min) intravenous (i.v.) infusion, followed by Lurbinectedin with starting dose of 1.0 mg/m\^2 as a 60-min (-5-min/+20-min) i.v. infusion followed by Irinotecan alone on Day 8 (at the same dose as Day 1 and as a 90-min \[-5-min/+30-min\] i.v. infusion)

Group II: Irinotecan Escalation Group Experimental Treatment 2 Interventions

Starting dose of Irinotecan 15 mg/m\^2 as a 90-min (-5-min/+30-min) i.v. infusion, followed by Lurbinectedin 3.0 mg/m\^2 as a 60-min (-5-min/+20-min) i.v. infusion followed by Irinotecan alone on Day 8 (at the same dose as Day 1 and as a 90-min \[-5-min/+30-min\] i.v. infusion).

Group III: Intermediate Escalation Group Experimental Treatment 2 Interventions

Starting dose of Irinotecan 50 mg/m\^2 as a 90-min (-5-min/+30-min) i.v. infusion, followed by Lurbinectedin 2.6 mg/m\^2 as a 60-min (-5-min/+20-min) i.v. infusion. No Irinotecan dose will be administered on Day 8 in this group.

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

Published Research Related to This Trial

Irinotecan, a derivative of camptothecin, shows promise when used in combination with fluorouracil (5-FU) for preoperative treatment of advanced rectal cancer, potentially enhancing treatment effectiveness.

The review discusses how both fluoropyrimidines and camptothecin can sensitize cancer cells to radiation, supporting the rationale for using these drugs together in combined-modality therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in preoperative combined-modality therapy for locally advanced rectal cancer. Mitchell, EP.[2018]

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]

Irinotecan is an approved treatment for colorectal cancer that does not respond to fluorouracil, highlighting its role in managing difficult cases of this disease.

The review addresses the drug's toxicity and management strategies, indicating that while irinotecan is effective, careful monitoring and handling of side effects are crucial for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Use of Irinotecan: Current Status and Future Considerations. Saltz, LB.[2019]

Irinotecan has shown significant activity against advanced colorectal cancer when combined with traditional chemotherapy agents like fluorouracil, leading to clinical responses including complete remissions in patients.

The combination therapies have acceptable toxicity profiles, with neutropenia and delayed diarrhea being the most common side effects, indicating that irinotecan could be a safe option for treatment, although further large-scale phase III studies are needed to confirm its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European experience with irinotecan plus fluorouracil/folinic acid or mitomycin. Khayat, D., Gil-Delgado, M., Antoine, EC., et al.[2018]

In a study of 61 patients with metastatic non-small-cell lung cancer (NSCLC), the combination of irinotecan (CPT-11) and etoposide (VP-16) resulted in a modest overall response rate of 21.3%, with a median survival time of 10 months.

The treatment was associated with manageable toxicities, including significant hematologic side effects like leukopenia and neutropenia in 23% and 39% of patients, respectively, but was comparable in efficacy to standard cisplatin-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of irinotecan and etoposide in patients with metastatic non-small-cell lung cancer. Oshita, F., Noda, K., Nishiwaki, Y., et al.[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]

Irinotecan has been extensively evaluated since its approval in 1996, with recent studies focusing on its use in combination chemotherapy regimens for treating colorectal and other gastrointestinal cancers, as well as lung cancers.

Research over the past five years has provided valuable insights into irinotecan's pharmacology, metabolism, and mechanisms of resistance, enhancing our understanding of how to optimize its use in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan (CPT-11): recent developments and future directions--colorectal cancer and beyond. Rothenberg, ML.[2019]

Irinotecan (CPT-11) demonstrated activity in treating recurrent malignant gliomas, with 15% of patients showing a confirmed partial response and 55% achieving stable disease for over 12 weeks, based on a study of 60 patients.

The treatment was associated with limited toxicity, primarily mild side effects like neutropenia and nausea, but the low plasma concentrations of the drug suggest that concurrent use of anticonvulsants and dexamethasone may reduce its effectiveness by enhancing drug clearance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan therapy in adults with recurrent or progressive malignant glioma. Friedman, HS., Petros, WP., Friedman, AH., et al.[2022]

Irinotecan is approved as a second-line treatment for metastatic colorectal cancer and has shown promising single-agent activity in Phase II studies for first-line treatment, with response rates comparable to standard regimens.

Due to its high cost and lack of definitive evidence showing superiority over current first-line treatments, routine use of irinotecan as a single agent may not be justified, although combination therapies with fluorouracil and molecular markers could help identify suitable patients for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in the first-line treatment of colorectal cancer. Saltz, LB.[2018]

Xiao-Chai-Hu-Tang (XCHT) effectively alleviates irinotecan (CPT-11)-induced diarrhea by reducing inflammation and improving the abundance of beneficial gut bacteria, as shown in a study with treated mice.

The active ingredient baicalein from XCHT selectively inhibits β-glucuronidase (β-GUS), a key enzyme linked to diarrhea caused by CPT-11, suggesting it could be a promising candidate for managing this side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insight into the mechanism of Xiao-Chai-Hu-Tang alleviates irinotecan-induced diarrhea based on regulating the gut microbiota and inhibiting Gut β-GUS. Wang, C., Teng, X., Wang, C., et al.[2023]

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sciencedirect.com

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The results showed that high rates of tumor response (82.6% in patients receiving the six cycles) and of liver metastasis resection (80.7%) could be achieved, ...

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cancernetwork.com/view/irinotecan-may-extend-survival-people-metastatic-colorectal-cancer

Irinotecan May Extend Survival in People With Metastatic ...

At 1 year, the overall survival rates were 45% in the irinotecan arm vs 32% in the 5-FU arm (P = .035). Quality-of-life analysis did not show a difference ...

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esmoopen.com

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pmc.ncbi.nlm.nih.gov/articles/PMC12184384/

Safety evaluation of irinotecan - PubMed Central

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pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/10211088/

Clinical activity and benefit of irinotecan (CPT-11) in ...

There was weight stabilisation or gain in 81% (73/90) of patients, a favourable outcome in PS in 91% (82/90) (improvement of WHO PS 2 or stabilisation of PS 0-1) ...

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/0959804996002936

Characterisation and Clinical Management of CPT-11 ...

In a pivotal French study in which CPT-11 350 mg/m 2 was administered once every 3 weeks, neutropenia and delayed diarrhoea were the major adverse events.