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

32 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment HIPEC + Surgery for Ovarian Cancer?

Research shows that combining cytoreductive surgery (removal of as much cancer as possible) with hyperthermic intraperitoneal chemotherapy (HIPEC, a heated chemotherapy treatment applied directly inside the abdomen) using drugs like cisplatin and paclitaxel can lead to favorable outcomes in treating advanced ovarian cancer. ^{1 2 3 4 5}

Is the combination of HIPEC and surgery for ovarian cancer safe?

The combination of paclitaxel and carboplatin, used in ovarian cancer treatment, is generally considered safe but can cause side effects like neutropenia (low white blood cell count), neurotoxicity (nerve damage), and fatigue. Replacing cisplatin with carboplatin reduces neurotoxic effects, making the treatment better tolerated and suitable for outpatient care. ^{6 7 8 9 10}

How does the HIPEC + Surgery treatment for ovarian cancer differ from other treatments?

The HIPEC + Surgery treatment for ovarian cancer is unique because it combines surgery with heated chemotherapy directly applied inside the abdomen, which has shown to significantly improve survival rates compared to other chemotherapy methods. This approach, using drugs like cisplatin and paclitaxel, is particularly effective for advanced stages of the disease. ^{1 3 5 11 12}

What is the purpose of this trial?

Community hospital based phase II (prospective randomized) study to evaluate the toxicity of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in newly diagnosed, otherwise untreated, advanced stage (stage III/IV) epithelial ovarian, fallopian tube, and primary peritoneal cancer.

Research Team

Armando Sardi, M.D.

Principal Investigator

Mercy Medical Center

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

Principal Investigator

Mercy Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 (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 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 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]

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]

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]

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]

References

1. 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]

2. Germany pubmed.ncbi.nlm.nih.gov

Neoadjuvant intraperitoneal chemotherapy with paclitaxel for the radical surgical treatment of peritoneal carcinomatosis in ovarian cancer: a prospective pilot study. [2015]

3. 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]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study. [2022]

5. 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]

6. England 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. [2020]

7. Ireland pubmed.ncbi.nlm.nih.gov

The feasibility of carboplatin-based intraperitoneal chemotherapy in ovarian cancer. [2022]

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

Taxane/platinum/anthracycline combination therapy in advanced epithelial ovarian cancer. [2015]

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

Treatment of ovarian cancer: current status. [2015]

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

Paclitaxel/carboplatin for the initial treatment of advanced ovarian cancer. [2015]

11. China pubmed.ncbi.nlm.nih.gov

Intraperitoneal chemotherapy for ovarian cancer with peritoneal metastases, systematic review of the literature and focused personal experience. [2021]

12. Turkey pubmed.ncbi.nlm.nih.gov

A Retrospective Clinical Analysis of Hyperthermic Intraperitoneal Chemotherapy in Gynecological Cancers: Technical Details, Tolerability, and Efficacy. [2022]