FF-10850 Topotecan Liposome Injection for Solid Tumors

Not currently recruiting at 6 trial locations

Overseen By FPHU Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 56

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called FF-10850, a special form of chemotherapy, to determine its safety and the optimal dose for treating advanced solid tumors like Merkel Cell Carcinoma. Researchers aim to assess the treatment's effectiveness and the maximum dose patients can tolerate without serious side effects. The trial includes different groups to test various doses. It suits those with advanced solid tumors who have tried other treatments without success and have been off chemotherapy or major treatments for at least three weeks. As a Phase 1 trial, this research focuses on understanding how FF-10850 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that FF-10850 Topotecan Liposome Injection is likely to be safe for humans?

Research shows that FF-10850, a new version of the drug topotecan, is being tested for safety in patients with advanced solid tumors. Topotecan already treats some cancers but can cause blood-related side effects. FF-10850, a liposome version, is designed to remain in the body longer and might reduce these side effects.

Earlier studies suggest that FF-10850 may work better for ovarian cancer than paclitaxel. However, detailed safety information from these studies is not yet publicly available. As the current trial is in its early stages, researchers are closely monitoring the treatment's safety. Participants might experience side effects similar to those of the original topotecan, but the hope is that this liposome version will be gentler on the body.

Prospective participants should discuss the possible risks and benefits with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about FF-10850 Topotecan Liposome Injection because it offers a new approach to treating certain solid tumors, like advanced ovarian cancer and Merkel cell carcinoma. Unlike standard chemotherapy, which often affects healthy cells, this treatment uses a liposome delivery system that targets cancer cells more precisely, potentially reducing side effects. Additionally, it delivers topotecan, a potent cancer-fighting drug, directly to the tumor site, which might enhance its effectiveness compared to traditional methods. The innovative combination of targeted delivery and a well-established anticancer agent could improve outcomes for patients with these challenging conditions.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that FF-10850, a special form of the drug topotecan, yields promising results in treating solid tumors. In earlier studies with ovarian cancer patients, this treatment reduced tumors in 20% of cases, compared to 13% with the common drug paclitaxel. More patients experienced tumor shrinkage with FF-10850. Additionally, patients using FF-10850 had a longer period before their cancer worsened. The special formulation of this drug targets the tumor more effectively and reduces side effects. Early findings suggest it may work well with other treatments, such as carboplatin or PARP inhibitors, to enhance its cancer-fighting effects. Participants in this trial will receive FF-10850 Topotecan Liposome Injection at various dose levels or the recommended phase 2 dose, depending on their assigned cohort. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• FF-10850 Topotecan Liposome Injection

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.

How Is the Trial Designed?

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

FF-10850 Topotecan Liposome Injection is already approved in European Union, United States for the following indications:

Approved in European Union as Hycamtin for:

• Ovarian cancer
• Cervical cancer
• Small cell lung cancer

Approved in United States as Hycamtin for:

• Ovarian cancer
• Cervical cancer
• Small cell lung cancer

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04047251

NCT04047251 | A Study of FF-10850 Topotecan Liposome ... Accrual for the dose-escalation and expansion phases is expected to be approximately 3 years, with patients followed every 3 months from the last dose of study ...

2. trials.braintumor.org trials.braintumor.org/trials/NCT04047251

A Study of FF-10850 Topotecan Liposome Injection in ... A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors Including Merkel Cell Carcinoma. Study Purpose. To determine the safety profile, ...

3. withpower.com withpower.com/trial/phase-1-neoplasms-10-2019-eeaa6

FF-10850 Topotecan Liposome Injection for Solid Tumors 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 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37683276/

FF-10850, a Novel Liposomal Topotecan Achieves ... FF-10850 significantly enhanced antitumor activity in combination with carboplatin or PARP inhibitor without detrimental effects on body weight ...

5. cancer.gov cancer.gov/clinicaltrials/NCI-2019-07108

A Study of FF-10850 Topotecan Liposome Injection in ... A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors Including Merkel Cell Carcinoma.

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-07108

A Study of FF-10850 Topotecan Liposome Injection in ... To determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended Phase 2 dose (RP2D) of FF-10850 (topotecan ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10690090/

FF-10850, a Novel Liposomal Topotecan Achieves Superior ... Topotecan, an approved treatment for refractory or recurrent ovarian cancer, has clinical limitations such as rapid clearance and hematologic toxicity.