What is the mechanism of action of this treatment?

Common treatments for Fallopian Tube Carcinoma often involve agents that inhibit tumor cell growth by targeting essential enzymes or cellular pathways. For example, pegylated SN-38 conjugate PLX038 works by blocking enzymes necessary for cell growth, thereby preventing tumor proliferation. Other treatments, such as platinum-based chemotherapies (e.g., carboplatin) and taxanes (e.g., paclitaxel), disrupt DNA replication and cell division. These mechanisms are crucial for patients because they directly target the rapid and uncontrolled growth of cancer cells, aiming to reduce tumor size and spread, ultimately improving patient outcomes.

What side effects are associated with this type of intervention?

Common treatments for Fallopian Tube Carcinoma, such as pegylated liposomal doxorubicin (PLD) and similar agents, often result in side effects including gastrointestinal issues (nausea, vomiting, mucositis), hematologic toxicities (anemia, neutropenia), and fatigue. Specific to PLD, patients may experience hand-foot syndrome, where the skin on the palms and soles becomes red and painful. Additionally, neurotoxicity, such as peripheral neuropathy, is a notable side effect, particularly with agents like paclitaxel. These side effects can vary in severity and impact the patient's quality of life.

What prior FDA approvals exist?

For the treatment of Fallopian Tube Carcinoma, several FDA-approved drugs target tumor cell growth by inhibiting essential enzymes. Notably, pegylated liposomal doxorubicin (PLD) and topotecan have been used in this context. PLD works by intercalating DNA and inhibiting topoisomerase II, leading to disrupted DNA replication and cell death. Topotecan inhibits topoisomerase I, preventing DNA unwinding necessary for replication. These treatments share a similar mechanism with the investigational agent Pegylated SN-38 Conjugate PLX038, which also aims to block enzymes critical for tumor cell growth.

What other types of research exist?

Promising novel alternatives to Pegylated SN-38 Conjugate PLX038 for Fallopian Tube Carcinoma patients include: 1) Bevacizumab combined with platinum-based chemotherapy followed by maintenance Bevacizumab, which inhibits angiogenesis. 2) PARP inhibitors such as Olaparib, especially for patients with BRCA mutations, which block DNA repair enzymes. 3) Combination therapies involving Bevacizumab and other agents like Topotecan or Pegylated Liposomal Doxorubicin, which have shown efficacy in recurrent ovarian cancer. These alternatives offer different mechanisms of action that may be beneficial for patients.

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Topoisomerase I inhibitor

PLX038 for Ovarian Cancer

Phase 2

Recruiting

Led By Scott H. Kaufmann, M.D., Ph.D.

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

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

Must have

Recurrent high grade serous ovarian cancer that was initially platinum sensitive (i.e., had at least one platinum-free interval of at least 6 months before progression) is now platinum resistant

Age >= 18 years NOTE: Because no dosing or adverse event data are currently available on the use of PLX038 in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials

Must not have

Histology other than high grade serous carcinoma

Chemotherapy =< 4 weeks prior to registration

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests PLX038, a drug that stops cancer cell growth, in patients with advanced ovarian, primary peritoneal, and fallopian tube cancers. The drug aims to shrink tumors by blocking enzymes needed for cancer cells to multiply.

Who is the study for?

This trial is for adults with high-grade serous ovarian, primary peritoneal, or fallopian tube cancer that's spread and resistant to platinum-based therapy. Participants need measurable disease, a life expectancy of at least 12 weeks, decent physical function (ECOG PS 0-2), acceptable blood counts and organ function. They must not have had more than one prior treatment for resistant disease and be willing to undergo biopsies.

What is being tested?

The trial is testing PLX038, a pegylated SN-38 conjugate designed to shrink tumors in metastatic cancers by blocking enzymes needed for cell growth. It includes CT scans and biospecimen collection like blood draws and tumor biopsies to study the drug's effects.

What are the potential side effects?

While specific side effects of PLX038 are not listed here, similar chemotherapy drugs can cause fatigue, nausea, diarrhea, low blood counts increasing infection risk; liver enzyme changes; allergic reactions; hair loss; mouth sores.

Eligibility Criteria

Inclusion Criteria

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

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My ovarian cancer came back and no longer responds to platinum-based treatments.

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I am 18 years old or older.

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I am able to care for myself and perform daily activities.

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My condition allows for two tissue samples to be safely taken.

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I have been diagnosed with a specific type of ovarian cancer.

Exclusion Criteria

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

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My cancer is not high grade serous carcinoma.

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I haven't had chemotherapy in the last 4 weeks.

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I do not have severe heart issues, uncontrolled diseases, or infections like HIV or hepatitis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 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

Proportion of confirmed tumor responses

Secondary study objectives

Incidence of adverse event rates

Overall survival (OS)

Progression-free survival (PFS)

Other study objectives

Correlative analyses

Gut microbiome analysis

Homologous recombination (HR) status

+2 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (pegylated SN-38 conjugate PLX038)Experimental Treatment4 Interventions

Patients receive PLX038 IV over 1 hour on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, biopsy, as well as blood and stool sample collection during screening and on the trial.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biopsy

2014

Completed Phase 4

~1090

Computed Tomography

2017

Completed Phase 2

~2740

Biospecimen Collection

2004

Completed Phase 3

~2020

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

Common treatments for Fallopian Tube Carcinoma often involve agents that inhibit tumor cell growth by targeting essential enzymes or cellular pathways. For example, pegylated SN-38 conjugate PLX038 works by blocking enzymes necessary for cell growth, thereby preventing tumor proliferation. Other treatments, such as platinum-based chemotherapies (e.g., carboplatin) and taxanes (e.g., paclitaxel), disrupt DNA replication and cell division. These mechanisms are crucial for patients because they directly target the rapid and uncontrolled growth of cancer cells, aiming to reduce tumor size and spread, ultimately improving patient outcomes.

Paclitaxel, Carboplatin and 1,25-D3 Inhibit Proliferation of Endometrial Cancer Cells In Vitro.Endometrial Cancers Harboring Mutated Fibroblast Growth Factor Receptor 2 Protein Are Successfully Treated With a New Small Tyrosine Kinase Inhibitor in an Orthotopic Mouse Model.Preclinical antitumor activity of a nanoparticulate SN38.