HIPEC with Surgery for Ovarian Cancer

(OVHIPEC-2 Trial)

Recruiting at 29 trial locations

Overseen By Lot Aronson

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: The Netherlands Cancer Institute

Disqualifiers: Previous malignancies, Stage IV disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

538 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding a heated chemotherapy treatment, called HIPEC, to surgery can more effectively treat stage III ovarian cancer. HIPEC involves applying heated chemotherapy directly to the abdomen during surgery. The researchers compare this method to standard surgery without HIPEC to determine which is more effective. Women with stage III epithelial ovarian, fallopian tube, or extra-ovarian cancer who are candidates for surgery might be suitable participants. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that using cisplatin with HIPEC, a heated chemotherapy treatment applied directly into the abdomen during surgery, is generally safe. One study found that even with multiple treatments, this approach did not increase post-surgery complications. Another study confirmed its safety and practicality, indicating no unexpected risks.

Cisplatin, a long-used chemotherapy drug, has well-known side effects. Most patients tolerate it well when combined with HIPEC, experiencing no severe side effects. However, as with any treatment, some negative effects may occur, which medical professionals closely monitor. Prospective trial participants should discuss any concerns with the healthcare team involved. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with surgery for ovarian cancer because it offers a unique approach by directly applying heated chemotherapy (cisplatin) to the abdominal cavity during surgery. This method allows for a higher concentration of the drug to target cancer cells more effectively, potentially reducing the side effects compared to traditional intravenous chemotherapy. Additionally, heating the chemotherapy enhances its cancer-killing effects, which may improve outcomes for patients with ovarian cancer. Unlike conventional surgeries that don't include HIPEC, this innovative approach could lead to better survival rates and has researchers hopeful for a significant advancement in treatment.

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

This trial will compare two treatment approaches for ovarian cancer: primary cytoreductive surgery with HIPEC using cisplatin, and conventional surgery without HIPEC. Studies have shown that applying HIPEC, which involves heated chemotherapy directly into the abdomen, with cisplatin after surgery can extend the lives of ovarian cancer patients. Research indicates that this combination increases the likelihood of living five more years for those with advanced ovarian cancer compared to surgery alone. HIPEC allows heated cisplatin to penetrate cancer cells more effectively, potentially enhancing its power. Several studies support the benefit of adding HIPEC to primary surgery in increasing survival rates. Overall, evidence suggests that HIPEC with cisplatin is a promising treatment option for advanced ovarian cancer. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with stage III epithelial ovarian, fallopian tube, or primary peritoneal cancer who are candidates for initial surgery to remove the tumor. They must not have had any other cancers in the past 5 years and should not have received prior treatment for their current cancer.

Inclusion Criteria

I am a candidate for major surgery to remove cancer.

My cancer is in stage III and started in the ovary, fallopian tube, or nearby areas.

Exclusion Criteria

My cancer is at the most advanced stage (stage IV).

I have received treatment for my current cancer.

I have not had any other cancers in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo primary cytoreductive surgery with or without HIPEC

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Long-term follow-up

Participants are monitored for long-term outcomes and cost evaluation

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
• Primary Cytoreductive Surgery

Trial Overview The study is testing whether adding hyperthermic intraperitoneal chemotherapy (HIPEC), which involves heating chemotherapy drugs and delivering them directly into the abdominal cavity, improves outcomes when combined with standard surgery compared to surgery alone.

How Is the Trial Designed?

Group I: HIPEC Experimental Treatment 1 Intervention

Primary cytoreductive surgery with HIPEC with cisplatin

Group II: conventional surgery Active Control 1 Intervention

Primary cytoreductive surgery without HIPEC

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

The Netherlands Cancer Institute

Lead Sponsor

Trials

308

Recruited

216,000+

Published Research Related to This Trial

In a study of 111 patients with stage IIIC-IV ovarian cancer, the use of HIPEC with either Paclitaxel or Cisplatin after cytoreduction did not show significant differences in disease-free survival outcomes, with median survival times of 27 months for Paclitaxel and 33 months for Cisplatin.

Factors such as incomplete cytoreduction and a higher Peritoneal Cancer Index (PCI >11) were identified as significant independent predictors of reduced disease-free survival, indicating that the effectiveness of HIPEC may be more influenced by surgical outcomes than by the choice of chemotherapy agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperthermic intraperitoneal chemotherapy with paclitaxel or cisplatin in patients with stage III-C/IV ovarian cancer. Is there any difference? Cascales-Campos, P., López-López, V., Gil, J., et al.[2022]

In a study of 41 patients with recurrent platinum-sensitive ovarian cancer, the combination of cytoreductive surgery (CRS) and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) was found to be a safe treatment, with a complication rate of 34.8% but no intraoperative deaths or deaths within 30 days post-surgery.

The treatment resulted in promising survival outcomes, with a median disease-free survival (DFS) of 24 months and overall survival (OS) of 38 months, indicating that CRS plus HIPEC significantly improves survival rates compared to standard chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIPEC in recurrent ovarian cancer patients: morbidity-related treatment and long-term analysis of clinical outcome. Fagotti, A., Costantini, B., Vizzielli, G., et al.[2022]

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 randomized trial involving 173 patients with advanced ovarian cancer, the combination of cisplatin (DDP) with Adriamycin (ADM) and Cyclophosphamide (CTX) was evaluated for its effectiveness.

The study reported high rates of side effects, with 90% of patients experiencing vomiting, 95% experiencing nausea, and 50% experiencing hair loss (alopecia), indicating that while the treatment may be effective, it also has significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness of cisplatin alone and in combination within the scope of primary therapy of ovarian cancer. Results of a prospective multicenter study]. Richter, P., Krafft, W., Müller, U., et al.[2013]

Cis-diamminedichloroplatinum (also known as cisplatin) is highly effective for treating stage III and IV ovarian cancers, suggesting it should be included in chemotherapy regimens.

The drug is particularly beneficial as a first-line treatment following surgical reduction of tumors in stage III ovarian cancer, enhancing the overall treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The value of cis-diamminedichloroplatinum (cis-platinum) CDDP in the treatment of stage III and IV cancers of the ovary (author's transl)]. Amiel, JL., Droz, JP., Tursz, T., et al.[2013]

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]

Cisplatinumdiamminodichloride (CPDD) showed significant effectiveness in treating various cancers, including embryonic carcinoma of the testes, ovarian carcinoma, melanoma, and epidermoid carcinoma, particularly in the head and cervix.

Due to its toxicity primarily affecting the digestive and renal systems, CPDD is recommended for use only in hospitalized patients and is indicated for combination therapy with other treatments for the specified tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatinumdiamminodichloride (CPDD) in chemotherapy of cancers: a phase II therapeutic trial. Hayat, M., Brulé, G., Cappelaere, P., et al.[2019]

Different platinum-based chemotherapeutic agents (CDDP, CBDCA, and CHIP) show varying effectiveness against different types of human ovarian cancers in a study using nude mice, highlighting the importance of personalized treatment based on tumor type.

For instance, while OVA-1 did not respond to CDDP, it was effectively treated with CBDCA and CHIP, indicating that selecting the right platinum analog is crucial for effective ovarian cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antitumor activity of platinum analogs against human ovarian tumors heterotransplanted into nude mice]. Sawada, M., Ozaki, M., Hongo, J., et al.[2013]

In a study of 16 patients with primary peritoneal carcinoma treated with a combination of paclitaxel and cisplatin, the chemotherapy resulted in significant tumor responses, including one complete pathologic response and three partial responses after initial cytoreductive surgery.

The findings suggest that the treatment regimen of paclitaxel and cisplatin is effective for primary peritoneal carcinoma, similar to its use in ovarian cancer, indicating a potential for similar therapeutic approaches in both conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically documented responses to paclitaxel and cisplatin in patients with primary peritoneal carcinoma. Menzin, AW., Aikins, JK., Wheeler, JE., et al.[2019]

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 of 350 patients undergoing cytoreductive surgery with cisplatin-based hyperthermic intrathoracic chemotherapy (HITOC), 12% experienced postoperative renal insufficiency, with a higher risk associated with high-dose cisplatin treatment.

The study found that patients receiving high-dose cisplatin were 2.7 times more likely to develop renal insufficiency compared to those receiving low-dose cisplatin, indicating that while the risk exists, it remains within an acceptable range.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperthermic Intrathoracic Chemotherapy (HITOC) after Cytoreductive Surgery for Pleural Malignancies-A Retrospective, Multicentre Study. Ried, M., Kovács, J., Markowiak, T., et al.[2021]

The combination of paclitaxel and cisplatin shows superior efficacy compared to standard therapy, leading to higher overall response rates and improved survival outcomes.

Adding cyclophosphamide to the paclitaxel/cisplatin regimen further enhances treatment results, and performing interval debulking surgery along with intraperitoneal therapy significantly improves overall survival in patients with residual disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Steps in the treatment of ovarian cancer]. Markowska, J.[2017]

In a study of 87 optimally debulked advanced ovarian cancer patients, TP therapy (cisplatin plus paclitaxel) did not show a significant survival advantage over CP therapy (cisplatin plus cyclophosphamide) for patients with a tumor rest of 2 cm or less.

While there was a non-significant trend suggesting a benefit of TP therapy in patients with larger tumor remnants (>2 cm), the overall findings indicate that a randomized trial is needed to further investigate the efficacy of these treatments given the high costs associated with TP therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is platinum-based chemotherapy with paclitaxel effective in optimally debulked patients with advanced ovarian cancer? Roovers, JP., Sijmons, EA., van Leeuwen, JH., et al.[2019]

Cis-dichlorodiammineplatinum(II) (cis-platinum) demonstrated response rates of 33% and 52% in 82 patients with advanced ovarian carcinoma when administered at doses of 30 mg/m2 and 100 mg/m2, respectively, indicating its efficacy as a treatment option.

In a randomized study of 58 previously untreated patients, a combination of chlorambucil and cis-platinum showed complete response rates of 32%, while adding Adriamycin increased the rate to 41%, with median remission durations exceeding 15 months for both regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer of the ovary: a summary of experience with cis-dichlorodiammineplatinum(II) at the Royal Marsden Hospital. Wiltshaw, E., Subramarian, S., Alexopoulos, C., et al.[2013]

Citations

1. 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12534361/

Intraperitoneal Perfusion with Cisplatin or Mitomycin C ... CRS-HIPEC has been shown to increase survival compared with CRS alone in studies in ovarian and colorectal cancer, but negative results have ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0960740424000859

A Clinician's perspective on the role of hyperthermic ... The application of HIPEC may potentially enhance the survival rates of patients with OC, as indicated by a recent publication of high-quality prospective data.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11671569/

Pharmacokinetics of cisplatin in the systemic versus ... The current study demonstrated that, in the perfusate, AUC0–24h and Cmax of cisplatin was significantly higher in the group of HITHOC compared ...

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24895230/

HIPEC ROC I: a phase I study of cisplatin administered as ... This phase I study tested the safety, feasibility, pharmacokinetics and pharmacodynamics of cisplatin administered as hyperthermic intraoperative ...

7. 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 ...