Surgery + HIPEC for Ovarian Cancer

No longer recruiting at 11 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Platinum-based chemotherapy

Must not be taking: Antineoplastic anti-hormonal therapy

Disqualifiers: Radiotherapy, Hepatitis, 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: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat ovarian cancer called HIPEC, which stands for hyperthermic intraperitoneal chemotherapy. After surgery to remove cancer, heated chemotherapy is applied directly inside the abdomen to target and kill remaining cancer cells. The trial compares patients receiving this treatment to those undergoing only surgery, aiming to determine if the heated chemotherapy makes a significant difference. This trial suits individuals with ovarian, fallopian tube, or primary peritoneal cancer that has returned more than six months after their last platinum-based chemotherapy treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does mention that certain anti-hormonal therapies are not allowed. It's best to discuss your specific medications with the trial team.

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

Research has shown that using carboplatin in heated chemotherapy (HIPEC) is generally safe for treating ovarian cancer. When heated and applied directly to the abdomen, carboplatin is usually well-tolerated. Blood-related side effects are manageable at the usual dose.

The FDA has already approved carboplatin for treating ovarian, fallopian tube, or primary peritoneal cancer, indicating it has been tested and found safe for these cancers, albeit in a different manner. In past studies, patients who received HIPEC with carboplatin did not experience unexpected side effects. While some side effects may occur, they are typically similar to those expected with chemotherapy, such as changes in blood cell counts.

Overall, evidence suggests that using carboplatin in HIPEC is a safe option for those considering this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining surgery with HIPEC (Hyperthermic Intraperitoneal Chemotherapy) for ovarian cancer because it offers a new way to directly target cancer cells in the abdomen. Unlike the usual systemic chemotherapy that circulates throughout the body, HIPEC delivers heated chemotherapy straight into the abdominal cavity during surgery. This unique approach allows for higher concentrations of the drug to reach the cancer cells with potentially fewer systemic side effects. Additionally, heating the chemotherapy can enhance its effectiveness in killing cancer cells. This method holds promise for improving outcomes for patients with recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer.

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

This trial will compare the effectiveness of secondary cytoreductive surgery with and without HIPEC for ovarian cancer. Research has shown that using HIPEC, which involves heated chemotherapy applied directly in the abdomen with the drug carboplatin, can improve outcomes for ovarian cancer when used after surgery. One study found that adding HIPEC increased the time patients lived without cancer returning from 10.7 months to 14.2 months. However, not all research indicates that HIPEC is superior in every situation, especially for recurrent cancers. Meanwhile, secondary cytoreductive surgery, which involves removing as much of the cancer as possible, has improved survival when no tumor remains, with complete removal achieved in 75% of patients. Both treatments in this trial aim to enhance survival and quality of life for ovarian cancer patients. ^{2 3 4 6 7}

Who Is on the Research Team?

Dennis Chi, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 21 with certain types of ovarian, fallopian tube, or primary peritoneal cancer that came back more than 6 months after platinum-based chemo. They should be healthy enough for surgery and more chemo, have a good performance status (able to care for themselves), and not have had other recent cancers or serious health issues like heart disease.

Inclusion Criteria

I am able to care for myself but may not be able to do active work.

My cancer returned within 30 months after treatment.

My bilirubin levels are within normal limits.

Exclusion Criteria

Patients with other concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or places them at an unacceptable risk for participation in the study

I have heart failure that affects my daily activities.

I have a significant immune deficiency, like AIDS or due to immunosuppressive medication after an organ transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and HIPEC

Secondary cytoreductive surgery with or without carboplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC)

1 week

1 visit (in-person)

Systemic Chemotherapy

Standard platinum-based systemic chemotherapy postoperatively (5 cycles in arm A and 6 cycles in arm B)

15-18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
• Platinum-based systemic chemotherapy postoperatively
• Secondary Cytoreductive Surgery

Trial Overview The study tests if adding heated chemotherapy directly into the abdomen (HIPEC) during surgery helps treat cancer better. Patients will get this treatment with carboplatin followed by standard platinum-based chemo. Researchers want to see if HIPEC improves outcomes compared to just having surgery and regular chemo.

How Is the Trial Designed?

Group I: Secondary Cytoreductive Surgery without HIPEC Experimental Treatment 2 Interventions

secondary cytoreductive surgery (CRS) with or without carboplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) followed by systemic combination chemotherapy for recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer. Patients will be randomized intraoperatively to undergo CRS with HIPEC (arm A) or CRS only (arm B) in a manner 1:1. Both arms will receive a standard platinum-based systemic chemotherapy postoperatively (5 cycles in arm A and 6 cycles in arm B).

Group II: Secondary Cytoreductive Surgery with HIPEC Experimental Treatment 3 Interventions

secondary cytoreductive surgery (CRS) with or without carboplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) followed by systemic combination chemotherapy for recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer. Patients will be randomized intraoperatively to undergo CRS with HIPEC (arm A) or CRS only (arm B) in a manner 1:1. Both arms will receive a standard platinum-based systemic chemotherapy postoperatively (5 cycles in arm A and 6 cycles in arm B). In some patients randomized to HIPEC at MSKCC only , peritoneal fluid and blood samples will be drawn before, during and after the HIPEC procedure.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Baptist Health South Florida

Collaborator

Trials

54

Recruited

8,100+

Hartford HealthCare

Collaborator

Trials

9

Recruited

1,300+

Published Research Related to This Trial

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]

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 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]

The study demonstrated that hyperthermic intraperitoneal carboplatin (HIPEC-carboplatin) is feasible and well-tolerated in 10 patients with recurrent, platinum-sensitive ovarian cancer following secondary cytoreductive surgery, with no intra-operative complications reported.

Post-operative adverse effects were mostly mild, with grade 1/2 nausea being the most common, and the majority of planned chemotherapy doses were successfully delivered, suggesting that HIPEC-carboplatin can be safely integrated into treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperthermic intraperitoneal chemotherapy with carboplatin for optimally-cytoreduced, recurrent, platinum-sensitive ovarian carcinoma: a pilot study. Argenta, PA., Sueblinvong, T., Geller, MA., et al.[2013]

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]

Carboplatin desensitisation therapy was successful in 93.4% of scheduled cycles, allowing patients with hypersensitivity reactions to continue receiving treatment for gynaecological cancer.

The therapy resulted in an 82.6% therapeutic response rate and a 95.7% disease control rate, demonstrating its efficacy and safety, as no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Adverse Events of Carboplatin Desensitisation Therapy for Gynaecological Cancer: A Retrospective Study. Yamamoto, A., Kamoi, S., Matsuda, S., 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8330970/

Secondary Cytoreduction and Carboplatin Hyperthermic ... HIPEC with carboplatin was well tolerated but did not result in superior clinical outcomes. This study does not support the use of HIPEC with ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1708618

Hyperthermic Intraperitoneal Chemotherapy in Ovarian ... The median recurrence-free survival was 10.7 months in the surgery group and 14.2 months in the surgery-plus-HIPEC group. At a median follow-up ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02124421

HOT: HIPEC in Ovarian Cancer as Initial Treatment Patients who meet study criteria will be randomized into one of two treatment arms: 1) cytoreductive surgery (CRS) with carboplatin-based hyperthermic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12071377/

An Updated Meta-Analysis on Long-Term Outcomes ... We found that hyperthermic intraperitoneal chemotherapy improves outcomes when used following neoadjuvant chemotherapy in primary cases and could lead to ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0748798325008522

Hyperthermic intraperitoneal chemotherapy (HIPEC) for ... HIPEC improved survival in primary ovarian cancer, especially after neoadjuvant chemotherapy. · No benefit from HIPEC in recurrent cases or without neoadjuvant ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7829861/

Pharmacokinetics and toxicity of carboplatin used for ... Carboplatin has a favorable pharmacokinetic profile for 90 min HIPEC administration, and the hematological toxicity was acceptable at dose 800 mg/m 2.

7. mayo.edu mayo.edu/research/clinical-trials/cls-20273187

Clinical Trials The drug used for HIPEC will be carboplatin, a Food and Drug Administration (FDA) approved drug for use in ovarian, fallopian tube or primary peritoneal cancer.