HIPEC + Surgery for Ovarian Cancer

(CRS/HIPEC Trial)

Overseen By Mary Caitlin King

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Mercy Medical Center

Disqualifiers: Other cancers, Hepatitis, HIV, Infection, 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: 11

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment approach for women with advanced ovarian, fallopian tube, or primary peritoneal cancer. Researchers aim to assess the safety and effectiveness of combining surgery with heated chemotherapy delivered directly inside the abdomen (known as Hyperthermic Intraperitoneal Chemotherapy), followed by standard chemotherapy. The goal is to determine if this method can improve outcomes compared to the usual treatment. Women who haven't received any prior treatment for these cancers and have stage III or IV disease might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking advancements in cancer care.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on full-dose warfarin, you may need to maintain a specific blood test range. It's best to discuss your medications with the trial team.

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

Research shows that combining cancer-removal surgery (CRS) with a special heated chemotherapy treatment (HIPEC) can be effective for advanced ovarian cancer. Previous studies have found that patients generally tolerate this treatment combination well.

In HIPEC, the chemotherapy drug carboplatin is used. Studies suggest that adding this heated chemotherapy to surgery can extend patients' lives. Participants in these studies did not experience significantly more severe side effects compared to surgery alone.

Overall, the combination of CRS and HIPEC appears safe, with no major safety issues reported in past research. Some minor side effects, such as temporary discomfort, might occur, but these are common with chemotherapy treatments.

Patients considering joining a trial can feel reassured that similar treatments have been studied and found to be safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) using carboplatin for ovarian cancer. Unlike standard treatments, which typically involve intravenous (IV) or intraperitoneal (IP) chemotherapy alone, this approach delivers heated chemotherapy directly into the abdomen during surgery. This method aims to target residual cancer cells more effectively and may enhance the penetration of the drug into tissues. Additionally, the use of HIPEC allows for a higher concentration of chemotherapy agents directly at the tumor site, potentially improving outcomes. This novel delivery method could offer a significant advantage over traditional chemotherapy regimens.

What evidence suggests that this trial's treatments could be effective for ovarian cancer?

This trial will compare two treatment approaches for advanced ovarian cancer. One group will undergo cytoreductive surgery (CRS) with adjuvant IV/IP chemotherapy, while another group will receive CRS combined with hyperthermic intraperitoneal chemotherapy (HIPEC) using carboplatin, followed by adjuvant IV chemotherapy. Studies have shown that combining surgery with HIPEC, a heated chemotherapy treatment, can extend the lives of patients with advanced ovarian cancer. Research indicates that patients who undergo both surgery and HIPEC experience longer periods without cancer recurrence compared to those who have surgery alone. In one study, survival rates were significantly higher for those receiving HIPEC, with a 33% increase in overall survival. Previous findings also show that using HIPEC with carboplatin is safe and can effectively enhance standard chemotherapy. Overall, the evidence suggests that this approach may lead to better outcomes for patients with advanced ovarian cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Armando Sardi, M.D.

Principal Investigator

Mercy Medical Center

Teresa Diaz-Montes, M.D., M.P.H

Principal Investigator

Mercy Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced stage (III/IV) ovarian, fallopian tube, or primary peritoneal cancer who haven't had treatment yet. They should be physically able to handle the procedures and have good organ function. Pregnant women, those with certain heart conditions, prior strokes or other cancers in the last 3 years are excluded.

Inclusion Criteria

My condition is in stage III or IV.

I haven't had treatment or major surgery for ovarian, fallopian tube, or peritoneal cancer, but diagnostic laparoscopy is okay.

My health allows me to receive chemotherapy after surgery.

Exclusion Criteria

I am currently on IV antibiotics for an infection.

I had a heart attack or other heart issue in the last 6 months.

I have moderate to severe heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cytoreductive Surgery (CRS) with/without HIPEC

Participants undergo cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy

1 week

1 visit (in-person)

Adjuvant Chemotherapy

Participants receive 6 cycles of adjuvant chemotherapy with either IV/IP or systemic IV combination chemotherapy

18 weeks

6 cycles, every 21 days

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

5 years

Baseline, 4 weeks post-operative, upon completion of chemotherapy, and annually up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Adjuvant Chemotherapy
• Carboplatin
• Cisplatin
• Cytoreductive Surgery (CRS)
• Hyperthermic intraperitoneal chemotherapy
• Paclitaxel

Trial Overview The study tests how safe and effective it is to combine cytoreductive surgery (CRS) with heated chemotherapy directly in the abdomen (HIPEC), followed by standard chemo. It's a phase II trial where patients are randomly assigned to treatments at a community hospital.

How Is the Trial Designed?

Group I: CRS/HIPEC with adjuvant IV chemotherapy Experimental Treatment 6 Interventions

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) administered using carboplatin for 90 minutes. Adjuvant systemic IV combination chemotherapy with carboplatin and paclitaxel (Carboplatin AUC 6, Paclitaxel 175mg/m2) will be given every 21 days for a total of 6 cycles. Administration of quality of life questionnaires throughout study duration of follow-up

Group II: CRS with adjuvant IV/IP chemotherapy Active Control 5 Interventions

Patients undergo cytoreductive surgery (CRS) alone with IV/IP combination adjuvant chemotherapy. Day 1: IV paclitaxel (135 mg/m2), day 2: IP cisplatin (75 mg/m2), and day 8: IP paclitaxel (60 mg/m2) given every 21 days for a total of 6 cycles. Standard of care treatment. Administration of quality of life questionnaires throughout study duration of follow-up

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Mercy Medical Center

Lead Sponsor

Trials

22

Recruited

4,400+

Published Research Related to This Trial

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) using cisplatin and paclitaxel is feasible for treating advanced epithelial ovarian cancer, with a high rate of complete cytoreduction (87%) observed in a study of 54 patients.

The procedure has an acceptable safety profile, with no intraoperative deaths and a median overall survival time of 32.91 months, although 61.1% of patients experienced disease recurrence during follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study. Coccolini, F., Campanati, L., Catena, F., et al.[2022]

In a study of 32 patients undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreductive surgery (CRS) for endometrial and epithelial ovarian cancer, the procedure showed a low operative mortality rate of 3% and a severe morbidity rate of 12%, indicating it is relatively safe.

Among the 30 patients with epithelial ovarian cancer, the 1-year overall survival rate was 69.7%, and for the platinum-resistant subgroup, the median overall survival was 14 months, suggesting that HIPEC can provide promising short-term outcomes even in challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Clinical Analysis of Hyperthermic Intraperitoneal Chemotherapy in Gynecological Cancers: Technical Details, Tolerability, and Efficacy. Minareci, Y., Tosun, OA., Sozen, H., et al.[2022]

In a study involving 13 women with epithelial ovarian cancer, hyperthermic intraperitoneal chemotherapy (HIPEC) using cisplatin and paclitaxel resulted in high drug concentrations in the peritoneal tissue while maintaining low levels in the bloodstream, indicating a favorable pharmacokinetic profile.

The treatment was associated with some surgical complications, with four patients experiencing grade 3-4 complications, but overall, HIPEC was deemed feasible and showed potential for effective localized treatment after cytoreductive surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer. Ansaloni, L., Coccolini, F., Morosi, L., et al.[2018]

The combination of paclitaxel and carboplatin showed an overall response rate of 42% in 73 patients with advanced ovarian cancer who had previously undergone platinum-based chemotherapy, indicating its efficacy as a treatment option.

While myelosuppression was the most common severe side effect, with significant rates of neutropenia, the therapy was generally well-tolerated, with only one case of febrile neutropenia and manageable levels of other toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the paclitaxel and carboplatin combination in patients with previously treated advanced ovarian carcinoma. A multicenter GINECO (Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens) phase II study. Guastalla, JP., Pujade-Lauraine, E., Weber, B., et al.[2020]

In a multicenter phase-I study involving 30 patients with initially unresectable ovarian cancer, the recommended dose of cisplatin for hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant chemotherapy was determined to be 70 mg/m², as higher doses led to significant dose-limiting toxicities (DLTs).

The study found that at the highest dose of 80 mg/m², there were serious adverse events including renal failure and hemorrhage, highlighting the importance of careful dose selection to minimize toxicity while maximizing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a multicenter phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer. Gouy, S., Ferron, G., Glehen, O., et al.[2022]

Carboplatin-based intraperitoneal (IP) chemotherapy is feasible for patients with ovarian cancer after surgery, with 73.7% of patients completing six or more cycles.

This regimen resulted in prolonged progression-free survival (26.6 months) compared to standard intravenous chemotherapy (20.7 months), while showing lower rates of gastrointestinal, neurologic, and metabolic toxicities compared to cisplatin-based IP chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The feasibility of carboplatin-based intraperitoneal chemotherapy in ovarian cancer. Kim, SW., Paek, J., Nam, EJ., et al.[2022]

In a study of 25 patients with advanced-stage ovarian cancer, cytoreductive surgery combined with carboplatin HIPEC showed no deaths or severe adverse events (grade 4-5), indicating a favorable safety profile.

While 44% of patients experienced at least one grade 3 adverse event, primarily infections and neutropenia, the overall morbidity was considered acceptable, supporting the feasibility of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morbidity after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with carboplatin used for ovarian, tubal, and primary peritoneal cancer. Mikkelsen, MS., Christiansen, T., Petersen, LK., et al.[2019]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12071377/

An Updated Meta-Analysis on Long-Term Outcomes ... We found that hyperthermic intraperitoneal chemotherapy improves outcomes when used following neoadjuvant chemotherapy in primary cases and could lead to ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2835694

Cisplatin- or Paclitaxel-Based HIPEC for Advanced ... The present study found that the use of HIPEC with paclitaxel was associated with similar outcomes as cisplatin, and thus, it may be a valuable ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8330970/

Secondary Cytoreduction and Carboplatin Hyperthermic ... HIPEC with cisplatin at 100 mg/m2 has been shown to be safe and cost effective and results in superior PFS and OS in patients with stage III ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1708618

Hyperthermic Intraperitoneal Chemotherapy in Ovarian ... The median recurrence-free survival was 10.7 months in the surgery group and 14.2 months in the surgery-plus-HIPEC group. At a median follow-up ...

5. jenci.springeropen.com jenci.springeropen.com/articles/10.1186/s43046-025-00286-y

Efficacy and safety of cytoreductive surgery combined with ... From 15 studies involving 1982 participants, OS analysis showed significantly higher survival in the CRS + HIPEC group (HR = 0.67, p < 0.0004).

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e17579

Evaluating the efficacy and safety of hyperthermic ... HIPEC as an adjunct to surgery demonstrates a significant survival benefit as compared to surgery alone in patients with advanced ovarian cancer.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0748798325008522

Hyperthermic intraperitoneal chemotherapy (HIPEC) for ... Therefore, we performed an updated meta-analysis of RCTs evaluating the efficacy and safety of cytoreductive surgery (CRS) with HIPEC compared to CRS without ...