Peposertib + Chemotherapy for Ovarian Cancer

Recruiting at 13 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

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

Compensation: Varies

Number of Visits: 30

Duration: Up to 3 years

54 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of peposertib when given together with pegylated liposomal doxorubicin hydrochloride in treating patients with high or low grade ovarian cancer that has come back after a period of improvement (recurrent). Peposertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving peposertib and pegylated liposomal doxorubicin hydrochloride may work better in treating patients with ovarian cancer compared to pegylated liposomal doxorubicin hydrochloride alone.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications and herbal supplements that interact with the study drug peposertib. Specifically, you must discontinue strong inducers/inhibitors of certain enzymes and proton-pump inhibitors at least 5 days before starting the trial. It's important to discuss your current medications with the study doctor to determine if they need to be stopped.

What data supports the effectiveness of the drug Peposertib + Chemotherapy for Ovarian Cancer?

Research shows that pegylated liposomal doxorubicin, a component of the treatment, is effective in treating ovarian cancer, especially in cases where the cancer is resistant to other treatments. It has been shown to have good activity against ovarian cancer with a favorable safety profile. ^{1 2 3 4 5}

What safety data exists for Peposertib + Chemotherapy in humans?

Pegylated liposomal doxorubicin (a form of chemotherapy) has been studied and found to have a better safety profile than its conventional form, with lower risks of myelosuppression (reduced bone marrow activity), cardiotoxicity (heart damage), and alopecia (hair loss). However, it may cause palmar-plantar erythrodysesthesia (PPE, a skin reaction on the hands and feet), so careful monitoring is recommended. ^{2 3 6 7 8}

What makes the drug Peposertib + Chemotherapy unique for ovarian cancer treatment?

The combination of Peposertib with pegylated liposomal doxorubicin (a form of chemotherapy) is unique because it aims to enhance the effectiveness of treatment while potentially reducing side effects compared to traditional doxorubicin. Pegylated liposomal doxorubicin is designed to improve delivery to cancer cells and reduce toxicity, making it a promising option for patients with recurrent or resistant ovarian cancer. ^{3 4 5 6 9}

Research Team

Rachel N Grisham

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Eligibility Criteria

This trial is for women with recurrent ovarian, fallopian tube, or primary peritoneal cancer. Participants must have had at least one prior platinum-based chemotherapy and can be of any age above 18. They should not be pregnant or breastfeeding and must agree to use contraception. People with certain heart conditions, uncontrolled illnesses, or those unable to take oral medication are excluded.

Inclusion Criteria

I have chronic hepatitis B but it's under control with treatment.

Your total bilirubin level should be no more than 1.5 times the upper limit of normal at the medical facility where you are being treated.

I have another cancer type, but it won't affect this treatment's safety or results.

Exclusion Criteria

Pregnant or breastfeeding women

Psychiatric illness/social situations that would limit compliance with study requirements

I have allergies to medications similar to peposertib or pegylated liposomal doxorubicin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive peposertib orally twice daily and pegylated liposomal doxorubicin intravenously on day 1. Cycles repeat every 28 days.

Up to 3 years

Every 28 days (in-person), CT/MRI every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

4 weeks

1 visit (in-person)

Long-term follow-up

Participants undergo ECHO or MUGA scan every 2 cycles starting in cycle 13 and are monitored for progression-free survival

Up to 3 years

Treatment Details

Interventions

• Pegylated Liposomal Doxorubicin Hydrochloride
• Peposertib

Trial Overview The study is testing the combination of a new drug called Peposertib with standard chemotherapy (pegylated liposomal doxorubicin hydrochloride) against ovarian cancer that has returned after treatment. The goal is to find out if this combo is more effective than the standard chemo alone.

Participant Groups

Group I: Treatment (peposertib, PLD) Experimental Treatment 7 Interventions

Patients receive peposertib PO BID on days 1-21, days 1-28, or days 1-7 (depending on dose level) and pegylated liposomal doxorubicin hydrochloride IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI during screening and every 8 weeks and after 6 months of study treatment, every 12 weeks. Patients undergo ECHO during screening and every 6 months. Starting in cycle 13, patients undergo ECHO or MUGA scan every 2 cycles. Additionally, patients undergo blood sample collection throughout the study.

Pegylated Liposomal Doxorubicin Hydrochloride is already approved in United States, European Union for the following indications:

Approved in United States as Doxil for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma

Approved in European Union as Caelyx for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma
• Breast cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase II trial involving 29 women with platinum-resistant or refractory epithelial ovarian cancer, Lipo-Dox demonstrated an overall response rate of 23.1%, with a median response duration of 11.6 weeks, indicating its efficacy in this challenging patient population.

The treatment was generally well-tolerated, with most side effects being mild (Grade 1/2), including hand-foot skin reactions (4.5%) and nausea (14.2%), suggesting a favorable safety profile for Lipo-Dox in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (Lipo-Dox) for platinum-resistant or refractory epithelial ovarian carcinoma: a Taiwanese gynecologic oncology group study with long-term follow-up. Chou, HH., Wang, KL., Chen, CA., et al.[2018]

In a phase II study involving 63 patients with ovarian cancer, pegylated liposomal doxorubicin (Doxil) showed a response rate of 19% in patients with measurable disease and a median overall survival of 10 months, indicating its efficacy in a heavily pretreated population.

Doxil was well tolerated, with manageable side effects; serious toxicities were relatively low, and nausea and vomiting were uncommon, suggesting a favorable safety profile compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of liposomal doxorubicin in advanced gynecologic cancers. Israel, VP., Garcia, AA., Roman, L., et al.[2013]

Pegylated liposomal doxorubicin (Doxil/Caelyx) showed a 26% objective response rate in pretreated ovarian cancer patients, leading to further studies confirming its effectiveness.

In a phase III trial comparing Caelyx to topotecan, both drugs demonstrated equivalent response rates and survival outcomes, but they differed in toxicity profiles, suggesting Caelyx could be integrated into first-line treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III data on Caelyx in ovarian cancer. Muggia, F., Hamilton, A.[2019]

This study analyzed over 7.5 million reports from the FDA Adverse Event Reporting System and found that conventional doxorubicin (DOX) has a higher incidence of adverse events compared to liposomal formulations, particularly in terms of myelosuppression and cardiotoxicity.

Liposomal DOX, especially the PEGylated version, showed lower reporting odds ratios for serious side effects like myelosuppression and cardiotoxicity, but a higher risk for palmar-plantar erythrodysesthesia (PPE), indicating the need for careful monitoring when using these formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system. Fukuda, A., Tahara, K., Hane, Y., et al.[2022]

In a phase I study involving 26 patients with advanced solid tumors, the combination of pegylated liposomal doxorubicin (Caelyx) and paclitaxel was found to be feasible, with a maximum tolerated dose established at 15 mg/m2 for Caelyx and 115 mg/m2 for paclitaxel, administered every two weeks.

The treatment regimen showed acceptable toxicity levels, with mild hematologic side effects and no significant cardiotoxicity, while achieving a complete response in one patient and partial responses in four, particularly among breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of paclitaxel (taxol) and pegylated liposomal doxorubicin (caelyx) administered every 2 weeks in patients with advanced solid tumors. Mavroudis, D., Kouroussis, Ch., Kakolyris, S., et al.[2018]

References

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

Treatment of patients with ovarian carcinoma with pegylated liposomal doxorubicin: analysis of toxicities and predictors of outcome. [2013]

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

Pegylated liposomal doxorubicin (Lipo-Dox) for platinum-resistant or refractory epithelial ovarian carcinoma: a Taiwanese gynecologic oncology group study with long-term follow-up. [2018]

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

Phase II study of liposomal doxorubicin in advanced gynecologic cancers. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin in the treatment of cancers of the breast and ovary. [2019]

5. Poland pubmed.ncbi.nlm.nih.gov

["Hand-foot" syndrome--after liposomal pegylated doxorubicin in patients with the ovarian cancer recurrence (own experiences)]. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Phase III data on Caelyx in ovarian cancer. [2019]

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

Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Phase I study of paclitaxel (taxol) and pegylated liposomal doxorubicin (caelyx) administered every 2 weeks in patients with advanced solid tumors. [2018]

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

GE11-Directed Functional Polymersomal Doxorubicin as an Advanced Alternative to Clinical Liposomal Formulation for Ovarian Cancer Treatment. [2019]