PLX038 for Ovarian Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: UGT1A1 inhibitors

Disqualifiers: Pregnancy, Heart disease, HIV, Hepatitis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Up to 18 weeks (6 cycles)

43 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether PLX038 (Pegylated SN-38 Conjugate) can shrink tumors in women with ovarian, primary peritoneal, or fallopian tube cancers that have spread. PLX038 blocks enzymes necessary for cancer cell growth. The trial seeks women whose ovarian cancer has returned and did not respond to platinum-based treatments after initially being sensitive to them. Participants should have undergone only one previous treatment for this type of cancer recurrence. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you require treatment with UGT1A1 inhibitors during the trial.

Is there any evidence suggesting that PLX038 is likely to be safe for humans?

Research shows that PLX038, the treatment under study, has been tested in other situations. One study found that PLX038 posed a low risk of causing serious side effects, particularly in the stomach and intestines, which are often a concern with cancer treatments. Patients who had already tried other treatments generally tolerated it well.

Although detailed safety data from the current study is not yet available, ongoing research suggests that PLX038 is manageable for most patients. For those considering joining a trial, this treatment appears to have a promising safety record based on past studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian cancer?

Unlike the standard treatments for ovarian cancer, which typically include surgery, chemotherapy, and targeted therapies, PLX038 uses a novel approach by delivering a pegylated SN-38 conjugate. This treatment is unique because it utilizes pegylation, a process that enhances the drug's stability and circulation time in the body, potentially leading to more effective targeting of cancer cells. Researchers are excited about PLX038 because it offers a new mechanism of action that could improve outcomes for patients who may not respond well to existing therapies.

What evidence suggests that PLX038 might be an effective treatment for ovarian cancer?

Research has shown that the drug PLX038, which participants in this trial will receive, might help shrink tumors in people with advanced ovarian and related cancers. PLX038 blocks certain proteins that cancer cells need to grow. Other studies have found that similar drugs can slow down or even stop tumor growth. Early results suggest that PLX038 could reduce tumor size and prevent cancer from spreading. Although some side effects like nausea and tiredness have been reported, the drug's potential to affect tumor growth remains promising. ^{1 2 4 6 7}

Who Is on the Research Team?

Andrea E. Wahner Hendrickson, M.D.

Principal Investigator

Mayo Clinic in Rochester

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

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Provide written informed consent

You are expected to live for at least 12 more weeks.

Women who could become pregnant must have a negative pregnancy test within 7 days before joining the study.

Exclusion Criteria

I have not had immunotherapy in the last 4 weeks.

Persons of childbearing potential who are unwilling to employ adequate contraception

I have not had radiotherapy in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive PLX038 intravenously over 1 hour on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Up to 18 weeks (6 cycles)

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and every 6 months for up to 5 years.

5 years

1 visit at 30 days, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Pegylated SN-38 Conjugate PLX038

Trial Overview 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.

How Is the Trial Designed?

Group I: Treatment (pegylated SN-38 conjugate PLX038) Experimental Treatment 4 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.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

CT-2103, a new drug combining paclitaxel and poly-L-glutamic acid, showed a 10% response rate in heavily pretreated patients with recurrent ovarian cancer, indicating some efficacy, especially in those with fewer prior treatments.

The treatment was associated with a notable incidence of neuropathy (30% of patients), which was higher than expected, suggesting the need for careful monitoring of side effects in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of CT-2103 in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Sabbatini, P., Aghajanian, C., Dizon, D., et al.[2017]

SN-38, a highly potent metabolite of irinotecan, has been successfully formulated into nanoparticles using a folate-conjugated polymer, enhancing its solubility and stability for potential clinical use.

These folate-targeted nanoparticles demonstrated significantly greater cytotoxicity against HT-29 cancer cells compared to non-targeted nanoparticles, suggesting they could be an effective delivery system for SN-38 in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation and in vitro evaluation of actively targetable nanoparticles for SN-38 delivery against HT-29 cell lines. Ebrahimnejad, P., Dinarvand, R., Sajadi, A., et al.[2022]

In a clinical trial involving 115 patients with ovarian, fallopian tube, and peritoneal cancer, PLD demonstrated a confirmed overall response rate (ORR) of 37.4%, indicating its efficacy in treating patients who experienced cancer progression after platinum-based therapy.

PLD was associated with a low frequency of severe adverse events, with only 3% of patients experiencing grade 3 or higher side effects, suggesting it is a safe treatment option that maintains a high quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin in patients with epithelial ovarian cancer. Yuan, Z., Zhang, Y., Cao, D., et al.[2023]

The study developed three antibody-drug conjugates (T-SN38 A, B, and C) that link the potent drug SN-38 to the anti-HER2 antibody trastuzumab, showing 2 to 3 times greater cytotoxicity against ovarian cancer cells compared to SN-38 alone.

In vivo tests revealed that all T-SN38 conjugates had significantly higher anti-ovarian cancer effectiveness than trastuzumab, with T-SN38 B demonstrating the best potency, indicating strong potential for treating HER2-positive ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis, characterization and targeting chemotherapy for ovarian cancer of trastuzumab-SN-38 conjugates. Yao, Y., Yu, L., Su, X., et al.[2018]

The new PEG-SN38 conjugate significantly improves the water solubility of SN38, increasing it by 400- to 1000-fold, which allows for better administration and potential effectiveness in treating cancer.

In preclinical tests, PEG-SN38 demonstrated anticancer activity comparable to native SN38 and superior efficacy compared to CPT-11 in a mouse model, making it a promising candidate for further development in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel prodrugs of SN38 using multiarm poly(ethylene glycol) linkers. Zhao, H., Rubio, B., Sapra, P., et al.[2022]

In a study of 30 patients with advanced ovarian cancer who had a complete response to initial chemotherapy, pegylated liposomal doxorubicin (PLD) was found to be a feasible consolidation therapy, with 79% of patients completing all four treatment cycles.

The treatment showed promising outcomes, with a median overall survival of 31 months and 47% of patients remaining disease-free at 4 years, although palmar-plantar erythrodysesthesia was the most common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin consolidation therapy after platinum/paclitaxel-based chemotherapy for suboptimally debulked, advanced-stage epithelial ovarian cancer patients. Rocconi, RP., Straughn, JM., Leath, CA., et al.[2018]

Labetuzumab govitecan (IMMU-130) significantly enhances the delivery of the active drug SN-38 to human colonic tumor xenografts, achieving up to 300-fold more SN-38 in tumors compared to irinotecan, while also minimizing exposure in normal tissues.

In preclinical studies with mice, IMMU-130 maintained higher serum levels of SN-38 over time and demonstrated a gradual release of the drug, indicating a more effective and potentially safer treatment option for targeting CEA-producing tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective and Concentrated Accretion of SN-38 with a CEACAM5-Targeting Antibody-Drug Conjugate (ADC), Labetuzumab Govitecan (IMMU-130). Sharkey, RM., Govindan, SV., Cardillo, TM., et al.[2020]

The bioconjugate ONCOFID-S, which links the drug SN-38 to hyaluronan, effectively targets ovarian cancer cells via the CD44 receptor, showing comparable tumor growth inhibition to free SN-38 in vitro.

In a mouse model, ONCOFID-S demonstrated improved therapeutic efficacy and better tolerability than the standard drug CPT-11, without causing inflammation, suggesting it could be a promising strategy for treating ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug conjugation to hyaluronan widens therapeutic indications for ovarian cancer. Montagner, IM., Merlo, A., Carpanese, D., et al.[2020]

Pegylated liposomal doxorubicin (PLD) has been an effective treatment for platinum-sensitive recurrent ovarian cancer, with clinical trials showing overall mean survival times of up to 29 months.

Combining PLD with carboplatin has shown similar effectiveness to other platinum-based therapies but with a better safety profile, and ongoing trials are exploring combinations with other innovative therapies to enhance its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of pegylated liposomal doxorubicin in the management of platinum-sensitive recurrent ovarian cancer: current concepts. Rakowski, JA., Ahmad, S., Holloway, RW.[2018]

The combination of trabectedin and pegylated liposomal doxorubicin (PLD) is effective for treating patients with partially platinum-sensitive recurrent ovarian cancer, especially those who have had multiple prior platinum-based treatments.

A case study of a 64-year-old woman showed that this combination therapy led to a sustained clinical response and good tolerance over more than two years, highlighting its potential as a viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance with Trabectedin in the Treatment of Platinum-Sensitive Recurrent Ovarian Cancer. Guerra Alía, EM., Sempere Ortega, C., Cortés Salgado, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05465941

Study Details | NCT05465941 | PLX038 for Treatment of ... This phase II trial tests whether pegylated SN-38 conjugate PLX038 (PLX038) works to shrink tumors in patients with ovarian, primary peritoneal, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3839288/

Phase I Dose-Escalation Study of EZN-2208 (PEG-SN38), a ... The most commonly reported drug-related adverse events were nausea (51%), diarrhea (46%), fatigue (41%), alopecia (29%), neutropenia (24%), and vomiting (22%).

3. withpower.com withpower.com/trial/phase-2-fallopian-tube-neoplasms-7-2022-5609d

PLX038 for Ovarian Cancer This trial tests PLX038, a drug that stops cancer cell growth, in patients with advanced ovarian, primary peritoneal, and fallopian tube cancers.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-04925

PLX038 for the Treatment of Patients with Metastatic ... This phase II trial tests whether pegylated SN-38 conjugate PLX038 (PLX038) works to shrink tumors in patients with ovarian, primary peritoneal, and fallopian ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00236

Dendrimer-Nanoparticle (DEP) Delivery of Topoisomerase ... This early-phase study evaluated safety/tolerability, pharmacokinetics, and preliminary efficacy of dendrimer-nanoparticle delivery platform ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04209595

PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors ... In this study, we use a new form of chemotherapy called PLX038 (PEGylated SN38) to see if it can be safely combined with PARP inhibitors to shrink tumors.

7. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/ProtocolDetails.aspx?id=2020-C-0013

NIH Clinical Center: Search the Studies To find a safe combination of PLX038 and rucaparib, and to see if this mix will cause tumors to shrink. Eligibility: People age 18 and older with solid tumors, ...