BAY 1895344 + Chemotherapy for Lung Cancer

Recruiting at 22 trial locations

Overseen By Thorvardur R. Halfdanarson

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Uncontrolled illness, Psychiatric illness, others

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

Compensation: Varies

Number of Visits: 3

Duration: 14-21 days per cycle

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the safety and best dose of a new drug combined with chemotherapy in patients with advanced solid tumors. The goal is to see if this combination can slow tumor growth more effectively than chemotherapy alone. The new drug blocks enzymes needed for tumor growth, while the chemotherapy drugs kill or stop the tumor cells from dividing. The chemotherapy drugs used in this trial are known to be effective in treating various cancers.

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

The trial does not specify if you need to stop all current medications, but you must stop taking strong CYP3A4 inhibitors at least 1 week before starting irinotecan therapy. It's important to discuss your current medications with the trial team to ensure there are no interactions.

What evidence supports the effectiveness of the drug BAY 1895344 combined with chemotherapy for lung cancer?

Irinotecan, a component of the treatment, has shown promising results in improving survival rates for small-cell lung cancer when combined with other drugs like cisplatin. It has also demonstrated effectiveness as a single agent and in combination with radiation therapy for both small-cell and non-small-cell lung cancer. ^{1 2 3 4 5}

Is the combination of BAY 1895344 and chemotherapy safe for humans?

Irinotecan, a component of the treatment, has been studied in various cancers, including lung cancer. Common side effects include nausea, vomiting, and esophagitis (inflammation of the esophagus). In some studies, severe side effects were observed at higher doses, but these were less common at moderate doses. ^{1 2 3 6 7}

What makes the drug BAY 1895344 + Chemotherapy for Lung Cancer unique?

The combination of BAY 1895344 with chemotherapy drugs like Irinotecan Hydrochloride and Topotecan Hydrochloride is unique because it involves a novel approach that may enhance the effectiveness of existing chemotherapy treatments for lung cancer, potentially improving patient outcomes compared to standard therapies. ^{1 2 3 4 8}

Research Team

Thatcher Heumann

Principal Investigator

Yale University Cancer Center LAO

Eligibility Criteria

Adults with advanced solid tumors, specifically small cell lung cancer, neuroendocrine carcinoma, or pancreatic cancer that have worsened after standard treatment. Must be able to swallow pills and not have severe heart disease. Eligible even if HIV-positive or with treated hepatitis B/C as long as it's under control. Cannot join if pregnant/breastfeeding or on certain drugs affecting liver enzymes.

Inclusion Criteria

My cancer treatment includes irinotecan or topotecan.

My kidney function, measured by GFR, is normal or above 60.

I can swallow pills.

Exclusion Criteria

Breastfeeding women

You have had allergic reactions to drugs like BAY 1895344 or other drugs being used in the study.

Pregnant women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive elimusertib and irinotecan or topotecan in cycles, with regular imaging and blood sample collection

14-21 days per cycle

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Every 2 months

Treatment Details

Interventions

• BAY 1895344
• Irinotecan Hydrochloride
• Topotecan Hydrochloride

Trial Overview The trial is testing the effectiveness of adding a new anti-cancer drug called BAY 1895344 to usual chemotherapy (irinotecan or topotecan). The goal is to see if this combination can better halt tumor growth compared to standard chemotherapy alone in patients with specific advanced cancers.

Participant Groups

Group I: Cohort III (elimusertib, topotecan) Experimental Treatment 6 Interventions

Patients receive elimusertib PO QD on days 2 and 5 and topotecan IV over 30 minutes on days 1-5 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT and/or MRI throughout the study, tumor biopsy at screening and on study, and collection of blood samples at screening.

Group II: Cohort II (elimusertib, irinotecan) Experimental Treatment 6 Interventions

Patients receive elimusertib PO QD on days 2, 3, 9, 10, 16, and 17 of cycle 1 and 2, and on days 2, 3, 9, and 10 of each cycle thereafter. Patients receive irinotecan IV over 90 minutes on days 1, 8, and 15 of cycle 1 and 2, and on days 1 and 8 of each cycle thereafter. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT and/or MRI throughout the study, tumor biopsy at screening and on study, and collection of blood samples at screening.

Group III: Cohort I (elimusertib, irinotecan) Experimental Treatment 6 Interventions

Patients receive elimusertib PO BID on days 1 and 2 and irinotecan IV over 90 minutes on day 1 of each cycle. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT and/or MRI throughout the study, tumor biopsy at screening and on study, and collection of blood samples at screening.

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

Approved in United States as Camptosar for:

• Colorectal cancer
• Pancreatic cancer

Approved in European Union as Irinotecan for:

• Colorectal cancer
• Pancreatic cancer

Approved in Canada as Camptosar for:

• Colorectal cancer
• Pancreatic cancer

Approved in Japan as Irinotecan for:

• Colorectal cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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, 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 (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

Current status of irinotecan in lung cancer. [2018]

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

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

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

Irinotecan in combination with radiation therapy for small-cell and non-small-cell lung cancer. [2018]

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

Topoisomerase I inhibitors in small-cell lung cancer. The Japanese experience. [2018]

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

Topoisomerase I inhibitors in the combined-modality therapy of lung cancer. [2018]

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

Weekly irinotecan and concurrent radiation therapy for stage III unresectable NSCLC. [2018]

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

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

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

Phase I/II study of weekly irinotecan and paclitaxel in patients with SCLC. [2018]