HIPEC for Recurrent Ovarian Cancer

Overseen By Mazdak Momeni, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Loma Linda University

Must be taking: Platinum-based chemotherapy

Disqualifiers: Invasive malignancies, Coronary artery disease, Hepatitis, Pulmonary disease, others

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

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called HIPEC, which involves bathing the inside of the abdomen with a warm chemotherapy solution, to determine its effectiveness in treating recurrent ovarian cancer. The trial aims to assess whether this method, combined with surgery and further chemotherapy, can effectively prevent cancer recurrence. Suitable candidates are those whose ovarian cancer has returned at least six months after their last platinum-based chemotherapy (such as Carboplatin) and are scheduled for another surgery. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this method is safe for treating recurrent ovarian cancer?

Research has shown that Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a safe treatment for ovarian cancer. In a study with 617 patients, most tolerated HIPEC well, experiencing no serious side effects. Another study also confirmed HIPEC's safety, reporting no major safety issues.

The HIPEC treatment in this trial uses carboplatin, a drug already approved for other cancers, indicating its general safety and well-known side effects. The treatment involves administering a heated solution of carboplatin into the abdomen to directly target cancer cells. While this might cause some discomfort, past studies suggest it is manageable.

Overall, evidence indicates that the HIPEC treatment in this trial is likely safe for participants. However, as with any treatment, individuals may experience different side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the HIPEC treatment for recurrent ovarian cancer because it introduces a unique delivery method. Unlike standard chemotherapy, which is typically administered intravenously, HIPEC bathes the abdominal cavity directly with a warm solution of anti-cancer drugs, such as carboplatin. This targeted approach allows for higher concentrations of the drug to be in direct contact with cancer cells, potentially improving effectiveness while reducing systemic side effects. Additionally, the heat used in HIPEC may enhance the cancer-fighting properties of the chemotherapy, offering a promising new angle for battling stubborn ovarian cancer recurrences.

What evidence suggests that HIPEC is effective for recurrent ovarian cancer?

Research shows that Hyperthermic Intraperitoneal Chemotherapy (HIPEC), combined with surgery, might help people with advanced ovarian cancer live longer. Some studies suggest that this combination can improve survival rates. However, results are mixed; other research has not found a clear benefit of HIPEC for recurrent ovarian cancer. Overall, while HIPEC appears promising, its effectiveness for recurrent ovarian cancer remains uncertain, with studies showing varying results on its impact on survival. ^{2 6 7 8 9}

Who Is on the Research Team?

Mazdak Momeni, MD

Principal Investigator

Loma Linda University Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 21 with recurrent ovarian, primary peritoneal, or fallopian tube cancers after initial platinum-based chemotherapy. They must have minimal residual disease post-surgery and be in good physical condition. Excluded are those with prior abdominal radiation, other recent cancers, low malignant potential tumors, heart disease, acute hepatitis, severe lung issues, compromised immune systems, known allergies to carboplatin or cisplatin, metastatic disease outside the abdomen or a life expectancy under 3 months.

Inclusion Criteria

My ovarian, peritoneal, or fallopian tube cancer has returned more than 6 months after platinum chemotherapy.

My organs are functioning properly.

My surgery left 2.5 mm or less of the disease.

Exclusion Criteria

My tumor is considered to be low-grade.

I have active heart artery disease.

I have been diagnosed with acute hepatitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Cytoreduction and HIPEC

Eligible patients undergo surgical cytoreduction followed by a single dose of carboplatin administered via intraperitoneal hyperthermic perfusion

1 day

1 visit (in-person)

Chemotherapy

Patients receive 6 cycles of standard IV platinum-based chemotherapy starting 4-6 weeks after CRS

18 weeks

Follow-up

Participants are monitored for recurrence-free survival with surveillance CT scans and serum CA-125 levels

18 months

4 visits (in-person) at 6, 9, 12, and 18 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Trial Overview

The study tests the effectiveness of combining surgical cytoreduction (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) using Carboplatin in patients with recurrent ovarian cancer. After surgery leaving ≤2.5 mm residual disease and HIPEC treatment at high temperatures for 90 minutes follows standard IV platinum-based chemotherapy cycles.

How Is the Trial Designed?

Group I: HIPEC Experimental Treatment 2 Interventions

A procedure in which the internal parts of your abdomen are bathed in a warm solution of anti-cancer medications for 90 minutes.

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?

Loma Linda University

Lead Sponsor

Trials

322

Recruited

267,000+

Published Research Related to This Trial

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]

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]

A systematic review of 23 studies on hyperthermic intraperitoneal chemotherapy (HIPEC) for first ovarian cancer relapse found that while median overall survival varied widely (23.5 to 63 months), the evidence supporting its efficacy is weak due to low-quality data.

Only 5 out of 8 case control studies showed significantly better overall survival for patients treated with HIPEC compared to those who were not, indicating that more rigorous research is needed to confirm its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Outcomes after Hyperthermic Intraperitoneal Chemotherapy for a First Ovarian Cancer Relapse: A Systematic Evidence-Based Review. Classe, JM., Asselain, B., Campion, L., et al.[2022]

In a study of 62 ovarian cancer patients undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin, the actual utilized dose (AD) of cisplatin was found to be 75.8 mg, representing a utility rate of 79.2% of the total dose administered.

Despite being able to predict the actual utilized dose of cisplatin using a regression equation, the study found that this dose did not have a significant impact on progression-free survival or overall survival for the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calculating the dose of cisplatin that is actually utilized in hyperthermic intraperitoneal chemotherapy among ovarian cancer patients. Wang, WY., Wu, MF., Wu, DB., et al.[2021]

The study of 96 patients undergoing cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemoperfusion (HIPEC) showed promising median overall survival rates of 78 months from diagnosis and 38 months post-procedure, indicating a potential survival benefit for patients with ovarian peritoneal metastases and primary peritoneal cancer.

While CRS-HIPEC demonstrated effectiveness, it also carried a risk of significant morbidity, with 23.4% of patients experiencing severe complications (Clavien-Dindo grade 3/4) and three patients dying within 60 days post-surgery, highlighting the need for careful patient selection and further prospective studies to define optimal treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperthermic intraperitoneal chemoperfusion as a component of multimodality therapy for ovarian and primary peritoneal cancer. Magge, D., Ramalingam, L., Shuai, Y., et al.[2018]

In a phase II study involving 98 patients with recurrent ovarian cancer, hyperthermic intraperitoneal chemotherapy (HIPEC) using carboplatin was found to be well tolerated, with no perioperative mortality and similar postoperative toxicity compared to standard treatment.

However, HIPEC did not demonstrate superior clinical outcomes, as the median progression-free survival was shorter in the HIPEC group (12.3 months) compared to the standard treatment group (15.7 months), leading to the conclusion that HIPEC with carboplatin is not recommended during secondary cytoreductive surgery for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study. Zivanovic, O., Chi, DS., Zhou, Q., et al.[2023]

In a study of 63 patients undergoing cisplatin (CDDP)-containing hyperthermic intraperitoneal chemotherapy (HIPEC), 66.1% experienced acute kidney injury (AKI), with the extent of parietal peritonectomy being a significant predictor of this complication.

Preclinical rat models showed that bilateral anterior parietal peritonectomy increased systemic absorption of CDDP by 1.6 to 2-fold, suggesting that careful consideration of CDDP dosage and concentration is crucial to minimize systemic toxicity and AKI risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extensive Peritonectomy is an Independent Risk Factor for Cisplatin HIPEC-Induced Acute Kidney Injury. Liesenfeld, LF., Quiring, E., Al-Saeedi, M., et al.[2023]

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]

The maximum tolerated dose (MTD) of carboplatin for intraperitoneal hyperthermic chemotherapy (IPHC) was established at 1000 mg/m², as higher doses led to significant toxicity.

Patients who received IPHC at the MTD were able to complete standard systemic chemotherapy afterward, and repeat IPHC was safely performed during second look surgeries without severe toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal hyperthermic chemotherapy using carboplatin: a phase I analysis in ovarian carcinoma. Lentz, SS., Miller, BE., Kucera, GL., et al.[2013]

Citations

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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].

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Use of HIPEC in recurrent ovarian cancer did not provide any survival advantage (5-year OS: 218 patients, RR = 0.85; 95% CI 0.45-1.62; P value = ...

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The most recent data also substantiates the effectiveness of HIPEC in recurrent ovarian cancer (ROC), resulting in an improvement of survival outcomes.

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

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Hyperthermic intraperitoneal chemotherapy (HIPEC) for the ...

Conversely, our results (from 617 randomized patients) indicate at level I evidence that HIPEC is a safe therapeutic modality, in any setting of ovarian cancer, ...

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The current study shows that HIPEC is a safe and reliable technique. But we don't know whether long-term exposure to low or even very low doses of chemotherapy ...

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HIPEC-based regimens improved the clinical prognosis for primary advanced OC, whereas no significant value was elicited for recurrent OC.

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Hyperthermic intraperitoneal chemotherapy (HIPEC) for the ...

Secondary outcomes are disease-free survival (DFS) for primary and PFS for recurrent ovarian cancer measured at consecutive time points, as well ...