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

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 with Surgery for Ovarian Cancer?

Research shows that combining cytoreductive surgery (removal of as much of the tumor as possible) with hyperthermic intraperitoneal chemotherapy (HIPEC) using cisplatin has favorable outcomes for advanced ovarian cancer. Additionally, cisplatin is effective in treating advanced stages of ovarian cancer, improving survival rates when used after surgery. ^{1 2 3 4 5}

Is HIPEC with surgery for ovarian cancer safe for humans?

The treatment involving cisplatin, used in HIPEC with surgery, has shown some side effects such as vomiting, nausea, and hair loss, and can affect the digestive and kidney systems. In a study, 12% of patients experienced kidney issues, with a small percentage needing temporary dialysis, but these risks were considered within an acceptable range. ^{6 7 8 9 10}

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

HIPEC with Surgery for ovarian cancer is unique because it combines surgery to remove as much of the tumor as possible (cytoreductive surgery) with heated chemotherapy (HIPEC) directly applied inside the abdomen, which may enhance the effectiveness of the chemotherapy and target cancer cells more directly compared to traditional intravenous chemotherapy. ^{3 11 12 13 14}

What is the purpose of this trial?

This trial tests if combining surgery with heated chemotherapy improves outcomes for patients with stage III ovarian cancer compared to surgery alone. Heated chemotherapy has shown improved disease-free and overall survival in patients with stage III ovarian cancer when combined with surgery to remove as much of the tumor as possible.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 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]

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]

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]

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]

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 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 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]

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]

References

1. Poland pubmed.ncbi.nlm.nih.gov

[Steps in the treatment of ovarian cancer]. [2017]

2. France 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)]. [2013]

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

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

4. Ireland pubmed.ncbi.nlm.nih.gov

Is platinum-based chemotherapy with paclitaxel effective in optimally debulked patients with advanced ovarian cancer? [2019]

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

Surgically documented responses to paclitaxel and cisplatin in patients with primary peritoneal carcinoma. [2019]

6. Germany 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]. [2013]

7. Germany pubmed.ncbi.nlm.nih.gov

Cisplatinumdiamminodichloride (CPDD) in chemotherapy of cancers: a phase II therapeutic trial. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Hyperthermic Intrathoracic Chemotherapy (HITOC) after Cytoreductive Surgery for Pleural Malignancies-A Retrospective, Multicentre Study. [2021]

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

Cancer of the ovary: a summary of experience with cis-dichlorodiammineplatinum(II) at the Royal Marsden Hospital. [2013]

10. Japan pubmed.ncbi.nlm.nih.gov

[Antitumor activity of platinum analogs against human ovarian tumors heterotransplanted into nude mice]. [2013]

11. Turkey pubmed.ncbi.nlm.nih.gov

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

12. Netherlands 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? [2022]

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

HIPEC in recurrent ovarian cancer patients: morbidity-related treatment and long-term analysis of clinical outcome. [2022]

14. Switzerland 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. [2023]