Surgery + HIPEC for Ovarian Cancer

Overseen By Aaron Shafer, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Investigational therapy

Disqualifiers: CNS metastases, Hypersensitivity to cisplatin, Uncontrolled illness, 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: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining surgery with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) can extend the lives of women with recurring primary mucinous ovarian cancer. The focus is on the effectiveness of this combined approach in improving survival after cancer recurrence. Women with a confirmed diagnosis of this specific type of ovarian cancer, who have experienced a recurrence, may be eligible for this trial. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, contributing to important advancements in cancer care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be more than 2 weeks from prior chemotherapy or radiation therapy, except for bevacizumab, which requires more than 6 weeks.

What prior data suggests that this surgery and HIPEC treatment is safe for ovarian cancer?

A previous study demonstrated that HIPEC (a type of heated chemotherapy applied directly inside the abdomen) is safe and reliable. While studies mainly focus on its impact on survival, they suggest that HIPEC is generally well-tolerated. No major safety concerns have been identified, but the long-term effects of the chemotherapy used in HIPEC remain unclear.

Research indicates that secondary surgery to remove ovarian cancer is generally safe. Complete tumor removal is often possible, and studies have not identified any major safety issues, suggesting that most patients handle the surgery well.

Both treatments have been tested in various studies and do not show significant safety problems. However, like any medical procedure, there can be risks. Always discuss possible side effects with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Hyperthermic Intraperitoneal Chemotherapy (HIPEC) combined with secondary cytoreductive surgery for ovarian cancer because it offers a unique approach compared to standard treatments. Unlike traditional chemotherapy, which circulates throughout the body, HIPEC delivers heated chemotherapy directly to the abdominal cavity immediately after surgery. This method allows for higher drug concentrations at the tumor site while minimizing systemic side effects. The heat may also enhance the effectiveness of the chemotherapy by increasing cancer cell sensitivity. This dual approach aims to improve outcomes by more effectively targeting residual cancer cells after surgical tumor removal.

What evidence suggests that surgery and HIPEC might be effective for ovarian cancer?

Research has shown that Hyperthermic Intraperitoneal Chemotherapy (HIPEC) might extend life when combined with surgery to remove advanced ovarian cancer. In one study, patients lived an average of about 54 months with HIPEC. However, other studies suggest that HIPEC's benefits for treating a first recurrence of ovarian cancer remain unclear.

In this trial, participants will undergo secondary cytoreductive surgery, which aims to remove as much cancer as possible. One study found that doctors removed all visible cancer in 75% of patients. Those who underwent this surgery lived longer, sometimes up to 42 months. Combining these treatments might improve outcomes for individuals with recurrent mucinous ovarian cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Aaron Shafer, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for women over 18 with recurrent primary mucinous ovarian cancer. They must have good organ and marrow function, be at least two weeks out from prior chemo or radiation (six weeks for bevacizumab), not pregnant or nursing, no history of HIPEC or intraperitoneal chemotherapy, and able to sign consent.

Inclusion Criteria

Your total bilirubin level should be less than 1.5 mg/dL.

I can take care of myself but might not be able to do heavy physical work.

Ability to understand and the willingness to sign a written informed consent document (either directly or via a legally authorized representative)

Exclusion Criteria

You are allergic to any of the ingredients in cisplatin.

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

I have had chemotherapy directly into my abdomen before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and HIPEC Treatment

Participants undergo secondary cytoreductive surgery followed by Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for recurrent mucinous ovarian cancer

1 week

Follow-up

Participants are monitored for progression-free survival, overall survival, and quality of life after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
• Secondary Cytoreductive Surgery

Trial Overview The study tests the effectiveness of secondary cytoreductive surgery combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in improving overall survival rates for women with this specific type of recurrent ovarian cancer.

How Is the Trial Designed?

Group I: Cytoreductive surgery Experimental Treatment 1 Intervention

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as HIPEC for:

• Appendix cancer
• Colorectal cancer
• Desmoplastic small round cell tumors
• Malignant ascites
• Mesothelioma
• Ovarian cancer
• Peritoneal cancer
• Stomach (gastric) cancer

Approved in European Union as HIPEC for:

• Appendix cancer
• Colorectal cancer
• Desmoplastic small round cell tumors
• Malignant ascites
• Mesothelioma
• Ovarian cancer
• Peritoneal cancer
• Stomach (gastric) cancer

Approved in Canada as HIPEC for:

• Appendix cancer
• Colorectal cancer
• Desmoplastic small round cell tumors
• Malignant ascites
• Mesothelioma
• Ovarian cancer
• Peritoneal cancer
• Stomach (gastric) cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In vitro studies showed that hyperthermic intraperitoneal chemotherapy (HIPEC) with temperatures above 40 °C significantly enhances the effectiveness of chemotherapy drugs like cisplatin and doxorubicin.

In a clinical setting, achieving and maintaining temperatures above 40 °C during HIPEC was associated with improved overall survival and progression-free survival in 68% of patients, highlighting the importance of temperature in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Temperature of 40 °C Appears to be a Critical Threshold for Potentiating Cytotoxic Chemotherapy In Vitro and in Peritoneal Carcinomatosis Patients Undergoing HIPEC. Schaaf, L., van der Kuip, H., Zopf, W., et al.[2016]

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment strategy for ovarian cancer that combines surgery with localized chemotherapy, aiming to improve outcomes for patients.

Current evidence from randomized trials on the effectiveness of HIPEC in ovarian cancer treatment is limited, highlighting the need for more comprehensive studies to assess its true impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperthermic intraperitoneal chemotherapy for the treatment of ovarian cancer: A brief overview of recent results. Roviello, F., Roviello, G., Petrioli, R., et al.[2016]

The study demonstrated the technical feasibility of performing hyperthermic intraperitoneal chemotherapy (HIPEC) using a laparoscopic approach in an animal model, specifically five adult pigs, indicating potential for less invasive treatment options.

The procedure successfully maintained adequate intraabdominal temperature and distribution of heated saline, suggesting that laparoscopic HIPEC could be a viable method for patients with minimal residual disease after surgery for stage III ovarian carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of laparoscopic peritonectomy followed by intra-peritoneal chemohyperthermia: an experimental study. Ferron, G., Gesson-Paute, A., Classe, JM., et al.[2015]

A study involving 584 patients with stage III epithelial ovarian cancer found that those who underwent primary cytoreductive surgery (PCS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) had a median survival time of 49.8 months, significantly longer than the 34.0 months for those who had PCS alone.

The 3-year overall survival rate was also higher for the PCS with HIPEC group at 60.3% compared to 49.5% for PCS alone, indicating that combining HIPEC with surgery can improve long-term outcomes for patients when complete surgical removal of the tumor is achievable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Stage III Epithelial Ovarian Cancer. Lei, Z., Wang, Y., Wang, J., et al.[2021]

Advanced haemodynamic monitoring and goal-directed fluid administration (GDFA) during hyperthermic intraperitoneal chemotherapy (HIPEC) are associated with significantly lower postoperative complications, shorter hospital stays, and reduced mortality compared to standard fluid administration, based on a review of existing studies.

The review indicates that there is considerable variability in intraoperative haemodynamic management practices for HIPEC, and that current renal protection protocols do not effectively reduce the risk of acute kidney injury (AKI).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haemodynamic management during hyperthermic intraperitoneal chemotherapy: A systematic review. Bezu, L., Raineau, M., Deloménie, M., et al.[2021]

In a study of 27 patients with recurrent ovarian cancer, 63% received hyperthermic intraperitoneal chemotherapy (HIPEC) after complete surgical cytoreduction, resulting in a high complete resection rate of 94% and no postoperative deaths.

The median disease-free survival after HIPEC was 11.9 months, and the median overall survival from diagnosis was 107.8 months, indicating that HIPEC is a feasible option with acceptable morbidity and promising survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Feasibility, morbidity and survival of surgery combined with HIPEC in the management of recurrent ovarian cancer]. Furet, E., Chéreau, E., Lambaudie, E., et al.[2013]

In a study of 10 patients undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery, 70% developed intra-abdominal adhesions during the closed-abdomen perfusion, which can hinder the effective distribution of the chemotherapy fluid.

The Laparoscopy-Enhanced HIPEC technique allows for early detection and division of these adhesions, potentially improving the treatment's efficacy by ensuring better circulation of the perfusion fluid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Onset of Intra-Abdominal Adhesions During Closed-Abdomen Hyperthermic Intraperitoneal Chemotherapy. Lotti, M., Giulii Capponi, M., Campanati, L., et al.[2018]

In patients with advanced epithelial ovarian cancer who underwent interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT), the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) significantly improved both progression-free survival (PFS) by 4.68 months and overall survival (OS) by 11.81 months compared to surgery alone, based on a review of 14 studies involving 1813 women.

However, in primary debulking surgery (PDS) and recurrent ovarian cancer (ROC), HIPEC did not show significant benefits in PFS or OS, and there was a slight increase in the risk of severe post-operative complications with the combined approach, indicating that while HIPEC can be beneficial in certain contexts, its role in other settings remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperthermic Intraperitoneal Chemotherapy (HIPEC): New Approaches and Controversies on the Treatment of Advanced Epithelial Ovarian Cancer-Systematic Review and Meta-Analysis. Della Corte, L., Conte, C., Palumbo, M., et al.[2023]

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]

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a safe treatment option for patients undergoing perioperative chemotherapy, ensuring safety for both patients and healthcare workers when standard protective measures are followed.

Current research indicates that various techniques for delivering intraperitoneal chemotherapy do not show significant differences in outcomes, suggesting that HIPEC is a reliable method among the available options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Techniques and Safety Issues for Intraperitoneal Chemotherapy. González-Moreno, S., Ortega-Pérez, G., Alonso-Casado, O., et al.[2018]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9456527/

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Complete PCS with HIPEC was associated with the best survival outcomes, with a median OS of 53.9 months and a 3-year OS rate of 65.9% [18,19].

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8750536/

Survival Outcomes after Hyperthermic Intraperitoneal ... Conclusions: There is no strong evidence to suggest efficacy of HIPEC in improving survival of patients treated for a first relapse of ovarian ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1015958424024886

Hyperthermic intraperitoneal chemotherapy: Ideal and reality The study found that multiple applications of HIPEC were safe and feasible and did not increase the incidence of postoperative complications. Therefore, we ...

4. mcgs.bcbsfl.com mcgs.bcbsfl.com/MCG?mcgId=01-96400-03&pv=false

Subject: Hyperthermic Intraperitoneal Chemotherapy (HIPEC) HIPEC is proposed to treat various abdominal cancers spreading to peritoneal lining like pseudomyxoma peritonei, mucinous adenocarcinoma of ...

5. gynecologiconcology-online.net gynecologiconcology-online.net/article/S0090-8258(25)00936-9/abstract

The role of hyperthermic intraperitoneal chemotherapy ... HIPEC might improve survival when combined with cytoreductive surgery in advanced ovarian cancer. · Evidence supports the efficacy of HIPEC in interval debulking ...

6. esmoopen.com esmoopen.com/article/S2059-7029(22)00216-2/fulltext

Hyperthermic intraperitoneal chemotherapy (HIPEC) for the ... HIPEC following neoadjuvant chemotherapy significantly increases 5-year overall survival in primary advanced ovarian cancer. •. HIPEC following ...

7. tandfonline.com tandfonline.com/doi/full/10.1080/02656736.2023.2165729

a systematic review and meta-analysis HIPEC-based regimens improved the clinical prognosis for primary advanced OC, whereas no significant value was elicited for recurrent OC.