Debio 0123 + Chemotherapy for Small Cell Lung Cancer

Recruiting at 15 trial locations

Overseen By Debiopharm International S.A

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Debiopharm International SA

Must not be taking: Investigational agents

Disqualifiers: Other malignancies, Cardiac issues, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

78 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary purpose of part 1 (dose escalation) of this study is to identify the recommended dose and to characterize the safety and tolerability of Debio 0123 in combination with carboplatin and etoposide. The primary purpose of part 2 (dose expansion) of this study is to characterize the safety and tolerability of Debio 0123 at the recommended dose when administered in combination with carboplatin and etoposide.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot have used an investigational agent or medical device within 28 days before starting the study treatment.

What data supports the effectiveness of the drug combination Debio 0123, carboplatin, and etoposide for treating small cell lung cancer?

Research shows that carboplatin and etoposide are effective in treating small cell lung cancer, with studies reporting high response rates and good tolerance. Adding paclitaxel to this combination has also shown increased efficacy, suggesting that similar combinations, like Debio 0123 with carboplatin and etoposide, could be promising. ^{1 2 3 4 5}

Is the combination of Debio 0123 and chemotherapy safe for humans?

The combination of carboplatin and etoposide, which are part of the treatment, has been shown to be generally well-tolerated in patients with small cell lung cancer, with manageable side effects like low blood cell counts and mild nausea. There were no life-threatening complications reported in the studies, indicating a moderate safety profile. ^{1 2 3 6 7}

What makes the drug combination of Debio 0123, Carboplatin, and Etoposide unique for treating small cell lung cancer?

The combination of Debio 0123 with Carboplatin and Etoposide is unique because Debio 0123 is a novel component that may enhance the effectiveness of the existing Carboplatin and Etoposide regimen, which is already known for its good tolerance and effectiveness in small cell lung cancer. This combination could potentially offer a new approach by incorporating Debio 0123, which might work differently from traditional chemotherapy drugs. ^{1 2 3 7 8}

Eligibility Criteria

Adults with small cell lung cancer that's come back or gotten worse after platinum-based therapy can join. They need a confirmed diagnosis, have had prior chemo, be in fairly good health (ECOG 0-1), and expect to live at least 3 more months. They must have measurable disease and not be dealing with major infections like HIV/HBV/HCV, significant heart issues, or other active cancers.

Inclusion Criteria

My tumor is not bleeding.

I am fully active or can carry out light work.

Life expectancy of at least 3 months in the best judgment of the Investigator

Exclusion Criteria

I have a stomach or intestine problem that affects how I absorb pills.

I am not allergic to Debio 0123, etoposide, carboplatin, or their ingredients, or I have successfully undergone desensitization for a carboplatin allergy.

I have or had Hepatitis B, C, or HIV but am cured if previously infected.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive Debio 0123 escalating doses, orally along with etoposide IV infusion and carboplatin IV infusion in 21-day cycles until disease progression or death or end of study

Variable (21-day cycles)

Dose Expansion

Participants receive Debio 0123 at the recommended dose, orally along with etoposide IV infusion and carboplatin IV infusion in 21-day cycles until disease progression or death or end of study

Variable (21-day cycles)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Carboplatin
• Debio 0123
• Etoposide

Trial Overview The trial is testing Debio 0123 combined with carboplatin and etoposide in two parts: first to find the safest dose (RP2D) and then to see how well patients tolerate it. It's for those whose cancer returned or progressed after initial treatment.

Participant Groups

Group I: Part 2: Dose Expansion: Debio 0123 + Etoposide + Carboplatin Experimental Treatment 3 Interventions

Participants will receive Debio 0123 recommended dose determined in Part 1 of the study, orally along with etoposide IV infusion and carboplatin IV infusion in 21-day cycles until disease progression or death or end of study.

Group II: Part 1: Dose Escalation: Debio 0123 + Etoposide + Carboplatin Experimental Treatment 3 Interventions

Participants will receive Debio 0123 escalating doses, orally along with etoposide IV infusion and carboplatin IV infusion in 21-day cycles until disease progression or death or end of study.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Debiopharm International SA

Lead Sponsor

Trials

53

Recruited

7,300+

Findings from Research

In a phase II trial involving 55 patients with limited-stage small cell lung cancer, the combination of paclitaxel, carboplatin, and etoposide showed promising efficacy, with 37.1% achieving a complete response and 51.4% a partial response.

The treatment was associated with moderate toxicity, primarily hematologic, but no life-threatening complications were reported, indicating that the regimen is tolerable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. Gatzemeier, U., Jagos, U., Kaukel, E., et al.[2015]

Carboplatin combined with etoposide (CarboEtop) shows a disease control rate of 74.5% in first-line treatment for advanced extra-pulmonary poorly-differentiated neuroendocrine carcinoma, indicating its effectiveness as a treatment option.

The treatment is generally well-tolerated, with myelosuppression being the most common severe side effect (49%), and no significant difference in toxicity between oral and intravenous etoposide, although there was a higher incidence of venous thromboembolism with oral etoposide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in Combination with Oral or Intravenous Etoposide for Extra-Pulmonary, Poorly-Differentiated Neuroendocrine Carcinomas. Frizziero, M., Spada, F., Lamarca, A., et al.[2020]

Carboplatin/etoposide is an effective treatment for small cell lung cancer, showing results comparable to the traditional cisplatin/etoposide combination, although it has not been directly compared in a randomized study.

This combination has a better safety profile, particularly in elderly patients, and lacks significant nonhematologic side effects, making it suitable for further studies involving dose escalation and bone marrow transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin/etoposide in small cell lung cancer. Bishop, JF.[2018]

In a phase III trial involving 614 patients with small-cell lung cancer, the combination of paclitaxel, etoposide, and carboplatin significantly improved overall survival and progression-free survival compared to the standard treatment of carboplatin, etoposide, and vincristine.

Patients receiving the experimental treatment experienced fewer severe hematologic toxicities, such as anemia and neutropenia, indicating a safer profile for the new combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase III trial of paclitaxel, etoposide, and carboplatin versus carboplatin, etoposide, and vincristine in patients with small-cell lung cancer. Reck, M., von Pawel, J., Macha, HN., et al.[2019]

In a study of 34 previously untreated patients with extensive small cell lung cancer, a combination of carboplatin and etoposide resulted in an objective response rate of 56%, with 16% achieving a complete response and 41% a partial response.

The treatment was generally well tolerated, with myelosuppression being the main side effect, but there were concerns about potential renal dysfunction and other side effects; however, the efficacy compared to the standard VP-16-cisplatin regimen remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VP-16 and carboplatin in previously untreated patients with extensive small cell lung cancer: a study of the National Cancer Institute of Canada Clinical Trials Group. Evans, WK., Eisenhauer, E., Hughes, P., et al.[2019]

A combination treatment of paclitaxel, carboplatin, and oral etoposide was found to be highly effective and well tolerated in 117 patients with small-cell lung cancer, showing promising results in both extensive and limited stages of the disease.

The regimen can be safely administered alongside thoracic radiation therapy, with only a few patients experiencing esophagitis, indicating a favorable safety profile compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, carboplatin, and extended-schedule oral etoposide for small-cell lung cancer. Hainsworth, JD., Hopkins, LG., Thomas, M., et al.[2015]

Carboplatin alone demonstrated a 20% response rate in previously untreated patients with advanced non-small cell lung cancer (NSCLC), indicating its effectiveness as a single-agent treatment.

The combination of carboplatin and etoposide showed a higher response rate of 26.7%, but it also resulted in significantly greater myelosuppressive toxicity, suggesting that while the combination is effective, it may come with increased side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II studies with carboplatin in non-small cell lung cancer. Gatzemeier, U., Heckmayr, M., Neuhauss, R., et al.[2018]

In a phase III trial involving 317 patients with small cell lung cancer, the carboplatin/etoposide/vincristine (CEV) regimen showed a significantly higher overall response rate of 79.8% compared to 59.8% for the etoposide/vincristine (EV) regimen (P < .001).

While the median survival was slightly longer for CEV-treated patients at 10 months versus 9 months for EV-treated patients, the difference was not statistically significant (P = .19), suggesting that patients with better prognostic factors should receive the more aggressive CEV treatment, while those with poorer factors may benefit from the less intensive EV regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide/vincristine-based chemotherapy with or without carboplatin in extensive-stage small cell lung cancer: a prospective randomized phase III trial. Gatzemeier, U., Pawel, JV., Laumen, R., et al.[2015]

References

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

Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. [2015]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Carboplatin in Combination with Oral or Intravenous Etoposide for Extra-Pulmonary, Poorly-Differentiated Neuroendocrine Carcinomas. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Carboplatin/etoposide in small cell lung cancer. [2018]

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

Randomized phase III trial of paclitaxel, etoposide, and carboplatin versus carboplatin, etoposide, and vincristine in patients with small-cell lung cancer. [2019]

5. England pubmed.ncbi.nlm.nih.gov

VP-16 and carboplatin in previously untreated patients with extensive small cell lung cancer: a study of the National Cancer Institute of Canada Clinical Trials Group. [2019]

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

Paclitaxel, carboplatin, and extended-schedule oral etoposide for small-cell lung cancer. [2015]

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

Phase II studies with carboplatin in non-small cell lung cancer. [2018]

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

Etoposide/vincristine-based chemotherapy with or without carboplatin in extensive-stage small cell lung cancer: a prospective randomized phase III trial. [2015]