HIPEC After Surgery for Ovarian Cancer

Overseen By Jill S Whyte, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Northwell Health

Must be taking: Platinum-based chemotherapy

Disqualifiers: Active second malignancy, Uncontrolled illness, Pregnant, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for women with advanced ovarian, fallopian tube, or primary peritoneal cancer. Researchers aim to determine if heated chemotherapy (HIPEC) during surgery can improve outcomes after initial chemotherapy. The trial uses Cisplatin, a chemotherapy drug, as part of the HIPEC procedure. It targets women whose cancer is confined to the abdomen and who have responded well to initial chemotherapy. The goal is to assess the treatment's safety and tolerability. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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 prior data suggests that HIPEC is safe for ovarian cancer patients?

Research has shown that using cisplatin in a heated chemotherapy treatment during surgery, known as HIPEC, has been safe for patients. Studies have found that adding HIPEC with cisplatin to surgery can extend the lives of patients with advanced ovarian cancer. Patients have generally tolerated this treatment well, managing any side effects.

Although some patients might experience side effects, the treatment is considered safe enough for testing in this trial. Cisplatin, a chemotherapy drug already approved by the FDA for other uses, offers some reassurance about its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike standard treatments for ovarian cancer, which often involve standard chemotherapy delivered intravenously, the use of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with Cisplatin delivers heated chemotherapy directly into the abdominal cavity. This method allows for a high concentration of the drug to target cancer cells more directly and intensively right after surgical tumor removal. Researchers are excited about this approach because it has the potential to improve drug penetration and effectiveness against any remaining cancer cells, thus possibly enhancing survival rates and reducing cancer recurrence.

What evidence suggests that HIPEC is effective for ovarian cancer?

Research has shown that HIPEC, a treatment where heated chemotherapy is applied directly to the abdomen, can improve outcomes for ovarian cancer patients. One study found that patients who received HIPEC after surgery lived for a median of 45.7 months, compared to 33.9 months for those who only had surgery. Another study discovered that using HIPEC after initial chemotherapy to shrink tumors can lead to better results in early cases. In this trial, participants will receive HIPEC with cisplatin, which may help extend life and reduce the chance of cancer recurrence. These findings offer hope for those with advanced ovarian cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Jill Whyte, MD

Principal Investigator

Northwell Health

Are You a Good Fit for This Trial?

This trial is for women over 18 with ovarian, fallopian tube, or peritoneal cancer who've had a positive response to initial chemotherapy. They must be in good heart and lung health, not pregnant or breastfeeding, without other cancers or severe illnesses that could interfere with the study.

Inclusion Criteria

My treatment is working as shown by tests or scans.

Your white blood cell count, neutrophil count, and platelet count are normal.

Your albumin levels are at least 2.5 mg/dL.

Exclusion Criteria

I have had chemotherapy or radiation for ovarian, fallopian tube, or peritoneal cancer.

I have another active cancer besides the one being studied.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive 3 cycles of neoadjuvant chemotherapy to assess response and eligibility for cytoreductive surgery

9 weeks

Interval Cytoreductive Surgery and HIPEC

Participants undergo interval cytoreductive surgery followed by heated intraperitoneal chemotherapy (HIPEC) with Cisplatin if optimal cytoreduction is achieved

1 week

Follow-up

Participants are monitored for safety, effectiveness, and adverse events after treatment

12 months

Monthly visits

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin

Trial Overview The trial tests heated intraoperative peritoneal chemotherapy (HIPEC) after three cycles of neoadjuvant chemotherapy (NACT) and surgery in patients whose tumors can potentially be completely removed. The focus is on feasibility and safety of HIPEC post-NACT.

How Is the Trial Designed?

Group I: HIPEC Experimental Treatment 1 Intervention

Patient will receive HIPEC in the form of Cisplatin 100mg/m2. 5. HIPEC will be provided at completion of surgical cytoreduction. The chemotherapy will be ordered by the treating gynecologic oncologist. It will be prepared in the chemotherapy pharmacy and delivered to the operating room once the surgeon confirms optimal cytoreduction and eligibility. Patients undergoing bowel resection will be left with bowel in discontinuity during the HIPEC infusion cycle. The abdomen will be temporarily closed with skin staples to prevent spillage of the perfusate. HIPEC will be delivered using the closed technique as has been well described.

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

Katie Oppo Research Fund

Collaborator

Trials

1

Recruited

20+

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 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]

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]

Cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion (HIPEC) at a dose of 100 mg/m² is safe and well-tolerated in patients with platinum-sensitive recurrent epithelial ovarian cancer, with only one out of six patients experiencing significant toxicity.

The study demonstrated favorable pharmacokinetics, with a mean peritoneal-to-plasma AUC ratio of 19.5, and confirmed the presence of cisplatin-induced DNA adducts in tumor samples, suggesting potential efficacy for HIPEC as a complementary treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIPEC ROC I: a phase I study of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion followed by postoperative intravenous platinum-based chemotherapy in patients with platinum-sensitive recurrent epithelial ovarian cancer. Zivanovic, O., Abramian, A., Kullmann, M., et al.[2019]

The maximum tolerated dose (MTD) of hyperthermic intraperitoneal cisplatin at 43°C for gynecological cancer patients was determined to be 85 mg/m2, based on a Phase I trial involving 30 patients.

Common adverse effects included nausea and vomiting in all patients, with significant risks of kidney injury and other dose-limiting toxicities observed at the highest dose level, indicating the need for careful monitoring of renal function during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Dose-Finding Trial for Hyperthermic Intraperitoneal Cisplatin in Gynecological Cancer Patients Receiving Hyperthermic Intraperitoneal Chemotherapy. Chan, CY., Li, H., Wu, MF., et al.[2021]

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]

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 Phase I study involving 40 patients with urologic and gynecologic cancers, cis-diamminedichloroplatinum(II) (CIS-DDP) was found to have manageable side effects, primarily nausea, vomiting, and anorexia, which resolved quickly after stopping the treatment.

The study indicated low levels of hematopoietic and renal toxicities, with no reported cases of hearing disturbances or tinnitus, suggesting a favorable safety profile for CIS-DDP at doses of 50 mg/m2 for single administration and 20 mg/m2/day for five consecutive days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2835694

Cisplatin- or Paclitaxel-Based HIPEC for Advanced ... These results could indicate that paclitaxel-based HIPEC is a safe and effective alternative to cisplatin for older patients, patients with ...

2. 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11898962/

Evaluating the Impact of Hyperthermic Intraperitoneal ... This narrative review evaluated the effectiveness of HIPEC combined with surgery and investigated its potential to improve survival, reduce recurrence, and ...

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

Hyperthermic Intraperitoneal Chemotherapy in Ovarian ... The median overall survival was 33.9 months in the surgery group and 45.7 months in the surgery-plus-HIPEC group. The percentage of patients who ...

5. mayoclinic.org mayoclinic.org/medical-professionals/obstetrics-gynecology/news/hipec-and-cytoreductive-surgery-do-not-improve-outcomes-over-cytoreductive-surgery-alone-in-patients-with-platinum-sensitive-recurrent-ovarian-cancer/mac-20525074

HIPEC and cytoreductive surgery do not improve ... A recently published multicenter, randomized phase 2 study failed to demonstrate benefit of HIPEC with carboplatin for platinum-sensitive recurrent ovarian ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05415709

Hyperthermic Intraperitoneal Chemotherapy With Cisplatin ... Giving hyperthermic intraepithelial chemotherapy with cisplatin after surgery or cisplatin before surgery may kill more tumor cells compared to usual care.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39878269/

Feasibility and safety of hyperthermic intra-peritoneal ... This study aimed to compare perioperative outcomes and progression-free and overall survival in patients with chronic kidney disease (CKD) versus those without