What side effects are associated with this type of intervention?

Treatments for solid tumors using topoisomerase I inhibitors like topotecan are commonly associated with hematologic toxicities such as neutropenia, thrombocytopenia, and anemia. Non-hematologic side effects can include fatigue, nausea, diarrhea, and alopecia. Severe cases may also experience febrile neutropenia and infections due to immunosuppression.

What prior FDA approvals exist?

Topotecan, a topoisomerase I inhibitor, has been FDA-approved for the treatment of ovarian cancer, small cell lung cancer, and cervical cancer. Irinotecan, another topoisomerase I inhibitor, is approved for colorectal cancer. These drugs work by interfering with DNA replication in cancer cells, leading to cell death. Both belong to the camptothecin family, which targets topoisomerase I.

What other types of research exist?

Promising novel alternatives to FF-10850 for solid tumor patients include: 1) Immunotherapy agents such as pembrolizumab and nivolumab, which have shown efficacy in various solid tumors by targeting PD-1/PD-L1 pathways. 2) Targeted therapies like larotrectinib and entrectinib, which are effective in tumors with specific genetic alterations (e.g., NTRK gene fusions). 3) PARP inhibitors such as olaparib and rucaparib, particularly for tumors with BRCA mutations. 4) Antibody-drug conjugates like trastuzumab deruxtecan for HER2-positive cancers. These alternatives represent significant advancements in the treatment of solid tumors and are expected to be relevant in 2024.

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Topoisomerase I inhibitor

FF-10850 Topotecan Liposome Injection for Solid Tumors

Phase 1

Recruiting

Research Sponsored by Fujifilm Pharmaceuticals U.S.A., Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically or cytologically confirmed metastatic and/or unresectable solid tumor, relapsed or refractory to standard therapy, or for which no standard therapy is available that is expected to improve survival by at least 3 months

At least 3 weeks beyond the last chemotherapy (or 3 half-lives, whichever is shorter), radiotherapy, major surgery, or experimental treatment, and recovered from all acute toxicities (≤ Grade 1), prior to the first dose of FF-10850

Must not have

Active infection requiring intravenous (IV) antibiotic usage within the last week prior to study treatment

Patients who have not received standard/approved therapies expected to improve survival by at least 3 months

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 4 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects for FF-10850 aren't listed here, typical reactions to topotecan can include lowered blood cell counts leading to increased infection risk or bleeding tendencies, fatigue, hair loss, nausea and vomiting.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

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My kidney function, measured by creatinine levels or clearance, is within the required range.

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My blood counts are stable without needing transfusions.

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I can carry out all my self-care but cannot do heavy physical work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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I have not had a serious heart condition in the last 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 4 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Determine incidence of Treatment Emergent Adverse Events

Determine maximun tolerated dose (MTD) of FF-10850

Determine recommended Phase 2 dose (RP2D) FF-10850

+1 more

Secondary study objectives

Characterize the pharmacokinetics (PK) of FF-10850 in plasma: AUC

Characterize the pharmacokinetics (PK) of FF-10850 in plasma: CL

Characterize the pharmacokinetics (PK) of FF-10850 in plasma: Cmax

+9 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: Cohort E5: Treatment at Recommended Phase 2 Dose (RP2D)Experimental Treatment1 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 Treatment1 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 3Experimental Treatment1 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 2Experimental Treatment1 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 1Experimental Treatment1 Intervention

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

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Topotecan, a common treatment for solid tumors, inhibits the enzyme topoisomerase I, which is essential for DNA replication. By blocking this enzyme, topotecan induces DNA damage in cancer cells, leading to their death. This mechanism is crucial for solid tumor patients as it specifically targets rapidly dividing tumor cells. Liposomal formulations, such as FF-10850, improve drug delivery to the tumor and reduce systemic toxicity, potentially enhancing treatment efficacy and minimizing side effects.

Synergistic cytotoxicity with 2'-deoxy-5-azacytidine and topotecan in vitro and in vivo.Phase II trial of topotecan in advanced or metastatic adenocarcinoma of the pancreas.Topotecan-induced topoisomerase IIalpha expression increases the sensitivity of the CML cell line K562 to subsequent etoposide plus mitoxantrone treatment.