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

15 Participants Needed

Trial Summary

What is the purpose of this trial?

The majority of women diagnosed with ovarian, fallopian tube and primary peritoneal cancer present with advanced stage III and IV disease. Despite aggressive surgery and systemic chemotherapy, the majority of patients will relapse. Five year survival remains only 20-35% for patients diagnosed with bulky stage IIIC and IV cancers. Patients who are not candidates for an initial cytoreductive surgery at the time of diagnosis form a particularly poor prognosis group. These patients are treated with neoadjuvant chemotherapy (NACT) and will ultimately undergo cytoreductive surgery provided there is a response to chemotherapy. New therapies for this cohort of women are urgently needed. The investigators have designed a pilot study to evaluate the feasibility of heated intraoperative peritoneal chemotherapy (HIPEC) given at the time of interval cytoreductive surgery after 3 cycles of NACT. Patients undergoing NACT for ovarian, fallopian tube or primary peritoneal cancer will be evaluated after their third cycle of chemotherapy for trial participation. Patient meeting eligibility criteria will proceed with cytoreductive surgery. HIPEC will be administered in those patients in whom optimal tumor cytoreduction is achieved. Primary objective of this study is to evaluate the feasibility, toxicity and tolerability of HIPEC administered after NACT.

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 drug cisplatin when used in HIPEC for ovarian cancer?

Research shows that cisplatin used in HIPEC (a heated chemotherapy treatment applied directly to the abdomen) has an acceptable safety profile and favorable properties in patients with recurrent ovarian cancer. The treatment was well-tolerated at certain doses, and it allowed for standard chemotherapy to be given afterward, suggesting it could be a helpful addition to ovarian cancer treatment. ^{1 2 3 4 5}

Is HIPEC with cisplatin safe for treating ovarian cancer?

HIPEC with cisplatin has been found to have an acceptable safety profile in patients with ovarian cancer, though common side effects include nausea, vomiting, and potential kidney injury. Some studies noted that kidney injury could progress to chronic kidney issues, especially at higher doses. ^{2 3 6 7 8}

How does HIPEC differ from other treatments for ovarian cancer?

HIPEC (Hyperthermic Intraperitoneal Chemotherapy) is unique because it involves directly administering heated chemotherapy drugs, like cisplatin, into the abdominal cavity during surgery, which allows for higher drug concentrations at the tumor site and potentially better outcomes compared to standard intravenous chemotherapy. ^{1 2 3 4 5}

Research Team

Jill Whyte, MD

Principal Investigator

Northwell Health

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

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 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]

References

1. 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]

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

Extensive Peritonectomy is an Independent Risk Factor for Cisplatin HIPEC-Induced Acute Kidney Injury. [2023]

3. United States 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. [2019]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Calculating the dose of cisplatin that is actually utilized in hyperthermic intraperitoneal chemotherapy among ovarian cancer patients. [2021]

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. Switzerland pubmed.ncbi.nlm.nih.gov

A Dose-Finding Trial for Hyperthermic Intraperitoneal Cisplatin in Gynecological Cancer Patients Receiving Hyperthermic Intraperitoneal Chemotherapy. [2021]

8. Japan pubmed.ncbi.nlm.nih.gov

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