FF-10850 Topotecan Liposome Injection for Solid Tumors

Recruiting at4 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.

Must not be taking: QTc prolonging drugs

Disqualifiers: Severe cardiac condition, Active CNS disease, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests a new form of a cancer drug called topotecan, which is packed in tiny fat bubbles to make it work better and be safer. It targets patients with advanced ovarian cancer and Merkel cell carcinoma who need new treatment options. The drug stops cancer cells from growing by attacking their DNA.

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

The trial protocol does not specify if you must stop all current medications. However, you cannot take medications that may cause QTc prolongation or induce Torsades de Pointes, unless they are essential for your care as determined by the Investigator.

What data supports the idea that FF-10850 Topotecan Liposome Injection for Solid Tumors is an effective drug?

The available research shows that FF-10850 Topotecan Liposome Injection, also known as Hycamtin, has demonstrated effectiveness in treating various types of cancer. For instance, in ovarian cancer, it showed a response rate of 20% compared to 13% for another drug, paclitaxel, and patients had a longer time before the disease progressed. In small cell lung cancer, it had a 39% response rate in patients who were sensitive to treatment. These results suggest that FF-10850 can be an effective option for certain cancers, with manageable side effects. ^{1 2 3 4 5}

What safety data is available for FF-10850 Topotecan Liposome Injection?

The safety data for topotecan, including its liposomal formulations, indicates that myelosuppression, primarily neutropenia, is the principal dose-limiting toxicity. Topotecan is generally well-tolerated with predictable and manageable side effects, mostly hematological. Liposomal formulations, such as PEGylated liposomal topotecan, have shown improved therapeutic efficiency and reduced toxicity compared to conventional formulations. However, further optimization and trials are needed to fully assess the safety and efficacy of these formulations. ^{1 3 5 6 7}

Is the drug FF-10850 Topotecan Liposome Injection a promising treatment for solid tumors?

Yes, FF-10850 Topotecan Liposome Injection shows promise as a treatment for solid tumors. It has been optimized to stay in the body longer, which can help it work better against cancer cells. Studies have shown it to be more effective than regular topotecan in treating certain cancers, like ovarian cancer, and it is being explored for use in other types of cancer as well. ^{1 2 4 6 8}

Research Team

Eligibility Criteria

Adults (≥18 years) with advanced solid tumors that are metastatic/unresectable, have failed standard treatments or have no better options. Participants must be recovered from previous therapies, have a life expectancy of ≥3 months, stable heart rhythm and adequate organ function. Pregnant/breastfeeding individuals, those with severe topotecan allergies, recent serious cardiac issues, active CNS malignancies or certain infections like HIV/HBV/HCV are excluded.

Inclusion Criteria

Hemoglobin (Hb) ≥ 9 g/dL

My cancer is advanced, cannot be surgically removed, and does not respond to standard treatments.

I have recovered from my last cancer treatment and it's been at least 3 weeks.

Exclusion Criteria

I have not used IV antibiotics for an infection in the last week.

I haven't had treatments known to extend life by 3 months.

Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation

Approximately 48 patients are planned for the dose-escalation phase to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of FF-10850.

3 years

Visits every 28 days

Cohort Expansion

Two additional cohorts are planned to be treated at the recommended Phase 2 dose (RP2D) for advanced ovarian cancer and Merkel cell carcinoma.

3 years

Visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up every 3 months to assess survival.

4 years

Treatment Details

Interventions

• FF-10850 Topotecan Liposome Injection (Topoisomerase I inhibitor)

Trial Overview The trial is testing FF-10850 Topotecan Liposome Injection to find the safest and most effective dose for treating advanced solid tumors. It aims to identify the maximum tolerated dose (MTD), any dose-limiting toxicities (DLTs), and recommend a Phase 2 dosage based on these findings.

Participant Groups

Group I: Cohort E5: Treatment at Recommended Phase 2 Dose (RP2D) Experimental Treatment 1 Intervention

For patients with advanced Merkel cell carcinoma: FF-10850 Topotecan Liposome Injection, RP2D administered intravenously (IV) on Days 1 and 15 of each 28-day cycle

Group II: Cohort E1: Treatment at Recommended Phase 2 Dose (RP2D) Experimental Treatment 1 Intervention

For patients with advanced ovarian cancer: FF-10850 Topotecan Liposome Injection, RP2D administered intravenously (IV) on Days 1 and 15 of each 28-day cycle

Group III: Cohort 3: Treatment at Dose Level 3 Experimental Treatment 1 Intervention

FF-10850 Topotecan Liposome Injection, Dose Level 3 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle

Group IV: Cohort 2: Treatment at Dose Level 2 Experimental Treatment 1 Intervention

FF-10850 Topotecan Liposome Injection, Dose Level 2 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle

Group V: Cohort 1: Treatment at Dose Level 1 Experimental Treatment 1 Intervention

FF-10850 Topotecan Liposome Injection, Dose Level 1 administered intravenously (IV) on Days 1 and 15 of each 28-day cycle

Who Is Running the Clinical Trial?

Fujifilm Pharmaceuticals U.S.A., Inc.

Lead Sponsor

Trials

9

Recruited

680+

No collaboration

Collaborator

Trials

3

Recruited

280+

Findings from Research

Topotecan, a topoisomerase-I inhibitor, was found to be highly effective against glioblastoma cell lines, showing no negative interaction when combined with ionizing radiation, indicating a potentially effective treatment strategy for this type of tumor.

In contrast, normal fibroblasts exhibited an antagonistic response to the combination of topotecan and radiation, suggesting that this treatment may be safer for normal tissues while still effectively targeting tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential response of tumor cells and normal fibroblasts to fractionated combined treatment with topotecan and ionizing radiation. Ohneseit, PA., Wildemann, A., Herskind, C., et al.[2013]

Topotecan is a promising topoisomerase I inhibitor that shows effectiveness in treating relapsed small-cell lung cancer (SCLC) and is being studied for first-line therapy in SCLC and non-small-cell lung cancer (NSCLC).

Current research is exploring the use of topotecan as a single agent and in combination therapies for various cancers, with a focus on developing a more convenient oral formulation and optimizing treatment regimens to improve patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future role of topotecan in the treatment of lung cancer. Schiller, JH.[2017]

Topotecan, a drug that targets topoisomerase I, has shown significant antitumor activity when combined with various chemotherapy agents like cisplatin and doxorubicin in both adult and pediatric patients with solid tumors.

The main side effect of these combination therapies is myelosuppression, particularly neutropenia, which limits the dosage; however, many early studies have reported major responses, indicating the potential effectiveness of these regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan in combination chemotherapy. Rowinsky, EK., Kaufmann, SH.[2017]

A retrospective study of 30 patients with recurrent ovarian cancer showed that long-term treatment with topotecan is feasible, with patients receiving an average of 14.4 cycles and a median time to treatment progression of 28 months.

Topotecan demonstrated a response rate of 53%, with manageable non-hematologic toxicity, suggesting it may provide a survival benefit for patients who continue treatment beyond six cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term topotecan therapy in recurrent or persistent ovarian cancer. Cormio, G., Loizzi, V., Gissi, F., et al.[2020]

Topotecan has demonstrated effectiveness in treating various cancers, including metastatic ovarian cancer and recurrent small cell lung cancer, with response rates of 20% in ovarian cancer compared to 13% for paclitaxel, and a notable median survival of 5.4 months in SCLC patients.

The drug is generally well-tolerated, with myelosuppression being the main side effect, but serious complications are rare, making it a manageable option for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan, an active new antineoplastic agent: review and current status. Carmichael, J., Ozols, RF.[2019]

An optimized liposomal formulation of topotecan, specifically using sphingomyelin/cholesterol (SM/Chol), showed significantly better drug retention and tolerability in mice compared to the previously used DSPC/cholesterol formulation.

This new formulation resulted in a 10-fold increase in plasma half-life and a 1000-fold increase in drug exposure over 24 hours, although it only modestly increased the lifespan of mice with neuroblastoma, indicating that further optimization may be needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of liposomal topotecan for use in treating neuroblastoma. Chernov, L., Deyell, RJ., Anantha, M., et al.[2022]

PEGylated liposomes (H-PEG) significantly enhance the effectiveness of topotecan against cancer cells, showing a 5-fold and 9-fold decrease in IC50 values for ovarian and colon cancer cells, respectively, compared to conventional liposomes.

In animal studies, H-PEG increased the accumulation of topotecan in tumors by 5.2 times compared to free topotecan and improved its therapeutic efficiency while reducing toxicity, suggesting that PEG-modified liposomes are a promising delivery system for this anti-cancer drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-vitro cytotoxicity, in-vivo biodistribution and anti-tumour effect of PEGylated liposomal topotecan. Hao, YL., Deng, YJ., Chen, Y., et al.[2018]

The newly developed liposomal nanoparticle formulation of topotecan, called Topophore C, achieved over 98% drug loading efficiency and significantly improved pharmacokinetics, with a 10-fold increase in plasma half-life and a 22-fold increase in area under the curve (AUC) compared to free topotecan.

Topophore C demonstrated enhanced anti-tumor activity against ovarian cancer models, being 2 to 3 times more toxic than free topotecan but showing better efficacy at doses that did not cause observable toxic effects, making it a promising candidate for further development, especially in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topophore C: a liposomal nanoparticle formulation of topotecan for treatment of ovarian cancer. Patankar, NA., Waterhouse, D., Strutt, D., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Differential response of tumor cells and normal fibroblasts to fractionated combined treatment with topotecan and ionizing radiation. [2013]

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

Future role of topotecan in the treatment of lung cancer. [2017]

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

Topotecan in combination chemotherapy. [2017]

4. Singapore pubmed.ncbi.nlm.nih.gov

Long-term topotecan therapy in recurrent or persistent ovarian cancer. [2020]

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

Topotecan, an active new antineoplastic agent: review and current status. [2019]

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

Optimization of liposomal topotecan for use in treating neuroblastoma. [2022]

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

In-vitro cytotoxicity, in-vivo biodistribution and anti-tumour effect of PEGylated liposomal topotecan. [2018]

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

Topophore C: a liposomal nanoparticle formulation of topotecan for treatment of ovarian cancer. [2021]