HIPEC After Surgery for Ovarian Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Jill Whyte, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Northwell Health

Must be taking: Platinum-based chemotherapy

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

Stay on Your Current Meds

No Placebo Group

Approved in 4 Jurisdictions

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.

Trial 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 (Alkylating agents)

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Long Island Jewish Medical Center New Hyde Park, NY

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Patients Recruited

470,000+

Katie Oppo Research Fund

Collaborator

Trials

1

Patients Recruited

20+

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] To compare the results of the administration of HIPEC with Paclitaxel or Cisplatin after cytoreduction in patients with stage IIIC-IV ovarian cancer, especially focused on disease-free survival.

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

Extensive Peritonectomy is an Independent Risk Factor for Cisplatin HIPEC-Induced Acute Kidney Injury. [2023] Cisplatin (CDDP)-containing hyperthermic intraperitoneal chemotherapy (HIPEC) is frequently applied in selected patients with peritoneal malignancies derived from ovarian cancer, gastric cancer, and primary peritoneal mesothelioma. HIPEC with CDDP increases perioperative morbidity, in particular by inducing acute kidney injury (AKI). Factors contributing to occurrence of AKI after intraperitoneal perfusion with CDDP have not been sufficiently evaluated.

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] This phase I study tested the safety, feasibility, pharmacokinetics and pharmacodynamics of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion (HIPEC) in patients with platinum-sensitive recurrent epithelial ovarian cancer (EOC) undergoing secondary cytoreductive surgery followed by postoperative platinum-based intravenous chemotherapy. Twelve patients with operable, recurrent platinum-sensitive EOC (recurrence ≥6 months after first-line therapy) were included according to the classical 3+3 dose-escalation design at three dose levels-60, 80 and 100 mg/m(2). After surgical cytoreduction, a single dose of cisplatin was administered via HIPEC for 90 min at 41-43°C. Postoperatively, all patients were treated with standard intravenous platinum-based combination chemotherapy. One of six patients experienced a dose-limiting toxicity (grade 3 renal toxicity) at a dose of 100 mg/m(2). The remaining five patients treated with 100 mg/m(2) tolerated their treatment well. The recommended phase II dose was established at 100 mg/m(2). The mean peritoneal-to-plasma AUC ratio was 19·5 at the highest dose level. Cisplatin-induced DNA adducts were confirmed in tumor samples. Common postoperative grade 1-3 toxicities included fatigue, postoperative pain, nausea, and surgical site infection. The ability to administer standard intravenous platinum-based chemotherapy after HIPEC was uncompromised. Cisplatin administered as HIPEC at a dose of 100 mg/m(2) has an acceptable safety profile in selected patients undergoing secondary cytoreductive surgery for platinum-sensitive recurrent EOC. Favorable pharmacokinetic and pharmacodynamic properties of HIPEC with cisplatin were confirmed at all dose levels, especially at 100 mg/m(2). The results are encouraging to determine the efficacy of HIPEC as a complementary treatment in patients with EOC.

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] Hyperthermic intraperitoneal chemotherapy (HIPEC) is advised as a treatment option for epithelial ovarian cancer (EOC) with peritoneal carcinomatosis. This study was designed to define the pharmacokinetics of cisplatin (CDDP) and paclitaxel (PTX) administered together during HIPEC.

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] Hyperthermic intraperitoneal chemotherapy (HIPEC) is an important treatment for ovarian cancer. A certain portion of cisplatin exits the body via the perfusate at the end of HIPEC, so full-dose utilization cannot be achieved. Herein, we sought to explore how much cisplatin is actually utilized and its prognostic influence.

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] The efficiency of cis Platin (DDP) alone and in combination with Adriamycine (ADM) and Cyclophosphamid (CTX) were evaluated in a prospective randomized trial containing 173 pat. suffering from advanced ovarian cancer (FIGO III/IV). Therapeutic schedule and results: (table; see text) The most side effects concerned vomiting (WHO Grad 2) in 90%, nausea (WHO Grad 2) in 95% and alopecia in 50% out of all pat.

7. Switzerland pubmed.ncbi.nlm.nih.gov

A Dose-Finding Trial for Hyperthermic Intraperitoneal Cisplatin in Gynecological Cancer Patients Receiving Hyperthermic Intraperitoneal Chemotherapy. [2021] Background: To identify the maximum tolerated dose (MTD) of hyperthermic intraperitoneal cisplatin at 43°C among gynecological cancer patients. Methods: In this Phase I dose-finding trial, Bayesian optimal interval (BOIN) design was used. We sought to explore the MTD with a target dose-limiting toxicity (DLT) rate of 20%, 4 prespecified doses (70 mg/m2, 75 mg/m2, 80 mg/m2 and 85 mg/m2), and 30 patients. Results: Between 2019 and 2020, 30 gynecologic cancer patients were enrolled. No patients received bevacizumab in subsequent treatment. The most common adverse events related to cisplatin were nausea and vomiting (100%), followed by tinnitus (26.7%) and kidney injury (23.3%). Of the seven patients with kidney injury, four had persistent renal impairment, and finally progressed into chronic kidney injury. DLTs were noted only in the dose level 4 group (85 mg/m2) and included acute kidney injury, pulmonary embolism, anemia, and neutropenia. When cisplatin was given at dose level four (85 mg/m2), the isotonic estimate of the DLT rate (22%) was closest to the target DLT rate of 20%. Therefore, 85 mg/m2 was selected as the MTD, with a 51% probability that the toxicity probability was greater than the target DLT rate. Conclusions: For gynecological cancer patients who received HIPEC for peritoneal metastases, the MTD of cisplatin in HIPEC at 43°C was 85 mg/m2. Our findings apply to patients who do not receive bevacizumab (ChiCTR1900021555).

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

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013] Phase I study of cis-diamminedichloroplatinum(II) (CIS-DDP) was performed in 7 institution's clinical group using 40 patients with histologically proven urologic and gynecologic malignancies. The most characteristic adverse effects were nausea, vomiting, and anorexia. With the cessation of administration they disappeared within one or two days. Manifestation of hematopoietic and renal toxicities were found low. Hepatotoxicities were slight. In this study there were no cases who showed hearing disturbances and tinnitus, which were reported in rather high percentages. Acceptable doses of CIS-DDP for single and 5 days' consecutive administration were estimated 50 and 20 mg/m2/day respectively.