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

3 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment HIPEC for recurrent ovarian cancer?

Research suggests that hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin, used during surgery for recurrent ovarian cancer, may improve outcomes. Studies indicate that HIPEC can provide a survival benefit without causing excessive short-term complications. ^{1 2 3 4 5}

Is HIPEC with carboplatin safe for treating recurrent ovarian cancer?

HIPEC with carboplatin has been studied for safety in treating ovarian cancer, showing some short-term risks like acute kidney injury, especially when combined with extensive surgery. However, it is generally considered safe enough to be used in clinical settings, with ongoing research to better understand and manage these risks. ^{1 2 6 7 8}

How is the HIPEC treatment for recurrent ovarian cancer different from other treatments?

HIPEC for recurrent ovarian cancer is unique because it involves delivering heated chemotherapy directly into the abdominal cavity during surgery, which can enhance the effectiveness of the drug carboplatin by increasing its absorption and targeting cancer cells more directly compared to traditional intravenous chemotherapy. ^{1 2 3 6 9}

What is the purpose of this trial?

This is a phase I prospective study with the primary objective to compare the efficacy and safety of Surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment of recurrent ovarian, primary peritoneal or fallopian tube cancers. Eligible patients consenting to this protocol will undergo their scheduled surgical procedure. After surgical cytoreduction to a residual disease ≤ 2.5 mm, a single dose of carboplatin (800 mg/m2) will be administered in normal saline via intraperitoneal hyperthermic perfusion using the closed-abdomen. HIPEC will be continued for 90 minutes in the hyperthermic phase (41°C-43°C). At 4-6 weeks after CRS, patients will go on to receive 6 cycles of standard IV platinum-based chemotherapy. The proportion of patients who are without evidence of recurrence will be assessed at 6, 9, 12 and 18 months after the day of surgery.

Research Team

Mazdak Momeni, MD

Principal Investigator

Loma Linda University Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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 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]

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]

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]

References

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

Morbidity after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with carboplatin used for ovarian, tubal, and primary peritoneal cancer. [2019]

2. United States 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. [2023]

3. United States 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. [2022]

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

Calculating the dose of cisplatin that is actually utilized in hyperthermic intraperitoneal chemotherapy among ovarian cancer patients. [2021]

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

Hyperthermic intraperitoneal chemoperfusion as a component of multimodality therapy for ovarian and primary peritoneal cancer. [2018]

6. England 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. [2018]

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

Intraperitoneal hyperthermic chemotherapy using carboplatin: a phase I analysis in ovarian carcinoma. [2013]

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

Extensive Peritonectomy is an Independent Risk Factor for Cisplatin HIPEC-Induced Acute Kidney Injury. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Survival Outcomes after Hyperthermic Intraperitoneal Chemotherapy for a First Ovarian Cancer Relapse: A Systematic Evidence-Based Review. [2022]