Hyperthermic Intraperitoneal Chemotherapy for Ovarian Cancer
Recruiting in Palo Alto (17 mi)
Overseen byFloor Backes, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Ohio State University Comprehensive Cancer Center
Must be taking: Carboplatin, Paclitaxel
Disqualifiers: Breast cancer, Inflammatory bowel disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
This phase I trial studies the side effects of hyperthermic intraepithelial chemotherapy with cisplatin after surgery or cisplatin before surgery in treating patients with stage III or IV ovarian, fallopian tube or peritoneal cancer receiving chemotherapy before surgery. Hyperthermic intraepithelial chemotherapy involves the infusion of heated cytotoxic chemotherapy that circulates into the abdominal cavity at the time of surgery. Chemotherapy drugs, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving hyperthermic intraepithelial chemotherapy with cisplatin after surgery or cisplatin before surgery may kill more tumor cells compared to usual care.
Do I need to stop my current medications for the trial?
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 Hyperthermic Intraperitoneal Chemotherapy for Ovarian Cancer?
Research shows that the combination of paclitaxel and carboplatin is effective in treating advanced ovarian cancer, with higher response rates and longer survival compared to other regimens. Paclitaxel is particularly active in patients resistant to platinum-based treatments, and carboplatin is preferred for its lower toxicity compared to cisplatin.12345
Is Hyperthermic Intraperitoneal Chemotherapy (HIPEC) safe for treating ovarian cancer?
Carboplatin and cisplatin, used in HIPEC, have been shown to be effective in treating ovarian cancer, with carboplatin generally causing fewer side effects like nausea and nerve damage compared to cisplatin. Paclitaxel, often combined with these drugs, is also effective but can cause side effects like low white blood cell counts and nerve damage. Overall, carboplatin is considered to have a more acceptable safety profile than cisplatin.23467
What makes hyperthermic intraperitoneal chemotherapy unique for ovarian cancer treatment?
Eligibility Criteria
This trial is for adults over 18 with stage III or IV ovarian, fallopian tube, or peritoneal cancer who've had some chemo but still need surgery. They should be fit for major surgery and have a good performance status score (0-2). People can't join if they have inflammatory bowel disease, recent other cancers except certain skin cancers and cervical carcinoma in situ, allergies to the drugs used here, or uncontrolled illnesses like heart failure.Inclusion Criteria
Your white blood cell count is higher than 3.5 billion cells per liter.
I can take care of myself and am up and about more than half of the day.
Your body has enough infection-fighting white blood cells.
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Exclusion Criteria
I haven't had cancer, except for certain skin cancers or cervical pre-cancer, in the last 5 years.
I do not have any uncontrolled illnesses like infections or heart problems.
I am not eligible if my surgery cannot remove or reduce my cancer significantly.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Neoadjuvant Chemotherapy
Participants receive carboplatin IV and paclitaxel IV on day 1, repeated every 3 weeks for 3-4 cycles
9-12 weeks
3-4 visits (in-person)
Interval Cytoreductive Surgery
Participants undergo interval debulking surgery, with randomization to receive cisplatin IV the day prior or HIPEC with cisplatin during surgery
1 day
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, including stool sample collection and diagnostic imaging
30 days
1-2 visits (in-person)
Long-term Follow-up
Participants are monitored for recurrence free survival and overall survival
3-5 years
Treatment Details
Interventions
- Carboplatin (Alkylating agents)
- Cisplatin (Alkylating agents)
- Cytoreductive Surgery (Other)
- Hyperthermic Intraperitoneal Chemotherapy (Other)
- Paclitaxel (Other)
Trial OverviewThe study tests two approaches: giving heated chemotherapy with cisplatin during surgery versus standard cisplatin before surgery. The goal is to see which method might kill more tumor cells effectively. Participants will also complete quality-of-life questionnaires to assess how these treatments impact their well-being.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm II (carboplatin, paclitaxel, CRS, HIPEC, cisplatin)Experimental Treatment9 Interventions
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients undergo HIPEC and receive cisplatin IV over 90 minutes at the time of CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
Group II: Arm I (carboplatin, paclitaxel, CRS, cisplatin)Experimental Treatment8 Interventions
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients receive cisplatin IV the day prior to CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Ohio State University Comprehensive Cancer CenterColumbus, OH
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Who Is Running the Clinical Trial?
Ohio State University Comprehensive Cancer CenterLead Sponsor
References
Paclitaxel plus carboplatin in the treatment of ovarian cancer. [2015]Two large, prospective randomized trials by the Gynecologic Oncology Group and the European Organization for Research and Treatment of Cancer have demonstrated the superiority of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/cisplatin compared with cisplatin/cyclophosphamide in previously untreated patients with advanced ovarian cancer. Patients receiving the paclitaxel combination had a higher overall response rate, a longer time to disease progression, and prolonged median survival. In an effort to reduce toxicity, investigators developed combinations of carboplatin/paclitaxel that were found by phase I/II trials to have activity comparable to cisplatin/paclitaxel but with less toxicity. Prospective randomized trials of paclitaxel/cisplatin versus paclitaxel/carboplatin were completed by the Gynecologic Oncology Group and by European investigators and preliminary results identify no differences in efficacy. Clinical trials of new combinations of paclitaxel/carboplatin with oral etoposide, gemcitabine, or epirubicin have recently begun. Additional studies of high-dose chemotherapy regimens of paclitaxel/carboplatin in untreated patients with optimal stage III ovarian cancer also are in progress. The Gynecologic Oncology Group has completed a randomized comparison of three versus six cycles of paclitaxel/carboplatin in early stage disease. This study will be followed by a trial in which all patients with poor-prognosis, early stage ovarian cancer receive three cycles of paclitaxel/carboplatin followed by randomization to no further treatment or to weekly paclitaxel. The combination of paclitaxel/carboplatin is currently the preferred regimen for the treatment of ovarian cancer.
Treatment of ovarian cancer: current status. [2015]Cytoreductive surgery followed by platinum-based combination chemotherapy has been standard therapy for patients with advanced epithelial ovarian cancer. Despite advances in surgery and in the development of a less toxic platinum compound (carboplatin), most patients with advanced ovarian cancer are not cured. Current clinical trials focus on dose-intense chemotherapy, routes and schedules of administration, and the role of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ). This novel agent has been shown to be highly active in patients with platinum-resistant ovarian cancer. Paclitaxel together with platinum (ie, cisplatin or carboplatin) combinations are now being tested in prospective randomized trials and in pilot studies in previously untreated patients with advanced disease.
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. [2020]Platinum compounds are the most active drugs in ovarian cancer treatment; cisplatin and carboplatin demonstrated similar efficacies but different toxicity profiles. Paclitaxel combined with cisplatin as first-line treatment improved overall survival when compared to a cisplatin-cyclophosphamide combination, but generated higher rates of neutropenia, febrile neutropenia and neurotoxicity. The paclitaxel-carboplatin combination may be better tolerated than cisplatin-paclitaxel.
Carboplatin versus cisplatin in ovarian cancer. [2015]The predominant data from clinical trials of advanced ovarian cancer have documented that carboplatin is equivalent to cisplatin in activity and causes considerably less ototoxicity, neurotoxicity, and nephrotoxicity. A large meta-analysis of over 2,000 patients entered into phase III clinical studies showed that patients with advanced ovarian cancer had virtually identical survival durations when treated with carboplatin- versus cisplatin-containing regimens. Furthermore, in the recent National Institutes of Health Consensus Conference on Ovarian Cancer, it was concluded that "data from mature randomized clinical trials have indicated that the combination of carboplatin and cyclophosphamide is effective therapy" and that "the substitution of carboplatin for cisplatin leads to more acceptable toxicity." Cisplatin appears to be the analog of choice for intraperitoneal therapy, which has proven superior to intravenous (IV) therapy in a recently completed intergroup study. Thus, both analogs are likely to play an important role in therapy of curative intent for patients with stage III, optimal disease. Now that paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has proven to be an essential first-line agent in combination with cisplatin or carboplatin in the management of previously untreated, advanced disease, several new strategies have been developed. In the setting of phase III clinical trials by the Gynecologic Oncology Group (GOG) and the Southwest Oncology Group's (SWOG) Gynecologic Cancer Committee, for example, GOG-114/SWOG-9227 compares the standard IV paclitaxel/cisplatin regimen to a dose-intensive regimen incorporating two courses of carboplatin (area under the concentration-time curve = 9 mg/mL/min) plus intraperitoneal cisplatin/IV paclitaxel. The planned GOG replacement for this study will compare the standard IV paclitaxel (24-hour infusion)/cisplatin regimen to a paclitaxel (3-hour infusion)/carboplatin regimen. In the SWOG, two different high-dose regimens followed by autologous bone marrow transplantation are being evaluated in the setting of a phase II randomized trial. These regimens include high-dose carboplatin/cyclophosphamide/mitoxantrone and high-dose cisplatin/cyclophosphamide/thiotepa. The results of these and other GOG and SWOG trials will dictate the management of advanced ovarian cancer through the end of the century.
Current status of chemotherapy for ovarian cancer. [2015]Standard treatment for patients with advanced ovarian cancer has been cytoreductive surgery followed by combination chemotherapy. Until recently, platinum-based chemotherapy was considered optimal and patients were treated with regimens built around either cisplatin or carboplatin. Recently, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been shown to be a highly active agent in refractory ovarian cancer patients. Subsequently, the Gynecologic Oncology Group performed a prospective randomized trial of paclitaxel plus cisplatin compared with cisplatin plus cyclophosphamide in suboptimal stage III and IV ovarian cancer patients. Based on higher response rates, longer time to progression, and marked improvement in median survival (37.5 months compared with 24.4 months), the Gynecologic Oncology Group currently considers paclitaxel plus cisplatin to be the new standard regimen for patients with advanced disease. More recently, paclitaxel plus carboplatin also has been evaluated in previously untreated patients. Using area under the curve dosing for carboplatin, it was demonstrated that this agent could be combined with paclitaxel (175 mg/m2 in a 3-hour infusion) with acceptable toxicity. All current Gynecologic Oncology Group protocols for untreated patients with ovarian cancer use a paclitaxel-based regimen. These clinical trials are evaluating the relative efficacy of carboplatin plus paclitaxel versus cisplatin plus paclitaxel as well as differences in dose and schedule and number of cycles of treatment. Investigational studies are continuing with high-dose chemotherapy that requires hematologic support as well as with intraperitoneal therapy (cisplatin or paclitaxel).
The feasibility of carboplatin-based intraperitoneal chemotherapy in ovarian cancer. [2022]To reduce toxicities in cisplatin-based intraperitoneal (IP) chemotherapy, we substituted carboplatin for cisplatin. The purpose of this study was to provide preliminary toxicity data of carboplatin-based IP chemotherapy and to evaluate the feasibility of this chemotherapy regimen in patients with ovarian cancer after primary debulking surgery.
Paclitaxel (175 mg/m2 over 3 hours) with cisplatin or carboplatin in previously untreated ovarian cancer: an interim analysis. [2015]The side effects of cisplatin (75 mg/m2) in combination with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (175 mg/m2 over 3 hours) are expected to be more severe and frequent than those of carboplatin (area under the concentration-time curve of 5) in combination with the same dose of paclitaxel, but the combinations are expected to be equally effective. A disadvantage of the cisplatin-based regimen is that patients need to be admitted to the hospital. The carboplatin regimen can be administered to outpatients. We tested both combinations administered every 3 weeks in a randomized phase III study in patients with previously untreated epithelial ovarian cancer. An interim analysis for toxicity was performed in 145 patients shortly after study closure. We observed a difference in the incidence of nausea, vomiting, and neurotoxicity favoring the women treated with the carboplatin regimen, but this regimen caused more myelotoxicity. Maturation of the study is awaited before survival data can be analyzed and final conclusions can be drawn.
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.
Intraperitoneal hyperthermic chemotherapy using carboplatin: a phase I analysis in ovarian carcinoma. [2013]Cyclic platinum-based intraperitoneal chemotherapy has proven to be effective after optimal surgical cytoreduction in ovarian carcinoma. Hyperthermia is directly cytotoxic and enhances chemotherapy tumoricidal effects. This study was designed to determine the maximum tolerated dose (MTD) of carboplatin used intraoperatively as intraperitoneal hyperthermic chemotherapy (IPHC), the effect on postoperative systemic chemotherapy administration, and the potential for repeat IPHC at second look surgery.
Treatment of ovarian cancer with paclitaxel- or carboplatin-based intraperitoneal hyperthermic chemotherapy during secondary surgery. [2015]We aimed to evaluate the efficacy and feasibility of treating advanced ovarian cancer with paclitaxel or carboplatin in intraperitoneal hyperthermic chemotherapy (IPHC) during secondary surgery.
Hyperthermic intraperitoneal chemotherapy with carboplatin for optimally-cytoreduced, recurrent, platinum-sensitive ovarian carcinoma: a pilot study. [2013]We aimed to evaluate the feasibility and tolerability of hyperthermic intraperitoneal carboplatin (HIPEC-carboplatin) following secondary cytoreduction for recurrent, platinum-sensitive ovarian cancer.
Cytotoxic effect of hyperthermia and chemotherapy with platinum salt on ovarian cancer cells: results of an in vitro study. [2013]Hyperthermic intraperitoneal chemotherapy is continuously under evaluation in ovarian cancer. The purpose of the present study was to evaluate the effect of chemotherapy, drug concentration and temperature.