Peposertib + Chemotherapy for Ovarian Cancer

Not currently recruiting at 13 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anthracyclines, PPIs, Sorivudine, others

Disqualifiers: Uncontrolled illness, Cardiac issues, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of a new drug, peposertib, with the chemotherapy drug pegylated liposomal doxorubicin to determine its effectiveness in treating ovarian cancer that has returned after treatment. The trial aims to find the optimal dose, understand any side effects, and assess whether this combination is more effective than the chemotherapy drug alone. Women whose ovarian cancer has recurred after treatment and who have undergone at least one round of platinum-based chemotherapy may be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug combination.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that peposertib is generally safe for people. In a study involving patients with advanced solid tumors, no major harmful effects appeared when peposertib was used alone. Another study found that peposertib was safe up to certain doses when combined with avelumab. The most common side effects were mild, such as tiredness and nausea.

Pegylated liposomal doxorubicin hydrochloride, a chemotherapy drug, has been in use for over 30 years and received FDA approval. Research has shown it is generally safe for patients with ovarian cancer, though it can cause side effects like skin reactions and mouth sores. Most of the time, these side effects can be managed.

Both treatments have a history of relative safety, but any concerns or questions should be discussed with a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of peposertib and pegylated liposomal doxorubicin hydrochloride (PLD) for ovarian cancer because it offers a novel approach compared to current treatments. While most standard therapies, like carboplatin and paclitaxel, focus on directly attacking cancer cells, peposertib targets the DNA damage response pathway, potentially enhancing the effectiveness of chemotherapy. Additionally, PLD is a unique formulation that allows the chemotherapy drug to circulate in the body longer, improving drug delivery to the tumor. This combination could lead to more effective treatment outcomes with potentially fewer side effects.

What evidence suggests that peposertib combined with chemotherapy might be an effective treatment for ovarian cancer?

In this trial, participants will receive a combination of peposertib and pegylated liposomal doxorubicin hydrochloride (PLD). Research has shown that combining peposertib with PLD may enhance ovarian cancer treatment. Peposertib blocks tumor growth, potentially increasing the effectiveness of PLD compared to its use alone. One study showed that this combination significantly reduced tumor growth, achieving a tumor control rate of 7.7%. PLD is already a well-known treatment for recurrent ovarian cancer, as it helps kill cancer cells and prevents their spread. Using these two treatments together could offer a stronger approach to managing ovarian cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Rachel N Grisham

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

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 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 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4049787/

Pegylated liposomal doxorubicin in the management of ... We performed a systematic review and metaanalysis to evaluate impact of PLD-based compared with no-PLD-based regimens in the ovarian cancer treatment.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2426807/

Pegylated liposomal doxorubicin in ovarian cancer - PMC This article reviews the mechanistic actions of this formulation, the Phase II and Phase III data that helped define the role of pegylated liposomal doxorubicin ...

3. bmjoncology.bmj.com bmjoncology.bmj.com/content/4/1/e000573

Thirty years from FDA approval of pegylated liposomal ... While PLD has gained a strong foothold in relapsed ovarian cancer and metastatic breast cancer, it has not been extensively tested in primary ( ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)37873-1/fulltext

Pegylated liposomal doxorubicin HCL (PLD; Caelyx/Doxil®) In this report, we describe the toxicity and outcome of 16 patients with gynecological cancer selected for having exceeded 1 year of maintenance treatment with ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2001.19.14.3312

A Randomized Phase III Study of Pegylated Liposomal ... A phase II study assessed the efficacy of pegylated liposomal doxorubicin in 89 patients with recurrent ovarian cancer who were unsuccessfully treated with ...

6. academic.oup.com academic.oup.com/oncolo/article/30/1/oyae194/7874888

Pegylated liposomal doxorubicin in partially platinum ... This study evaluated the efficacy and safety of pegylated liposomal doxorubicin for patients with partially platinum-sensitive, ...