Hyperthermic Intraperitoneal Chemotherapy for Ovarian Cancer

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Ohio State University Comprehensive Cancer Center

Must be taking: Carboplatin, Paclitaxel

Disqualifiers: Breast cancer, Inflammatory bowel disease, others

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

Compensation: Varies

Number of Visits: 5

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment for advanced ovarian, fallopian tube, or peritoneal cancer using heated chemotherapy (Hyperthermic Intraperitoneal Chemotherapy). The researchers aim to determine if combining heated chemotherapy with surgery can more effectively kill cancer cells compared to standard treatments. Participants will receive chemotherapy drugs like carboplatin and paclitaxel, with some also receiving heated chemotherapy with cisplatin during surgery. This trial suits those newly diagnosed with stage III or IV ovarian-type cancers who are already undergoing chemotherapy before surgery. It seeks to improve outcomes and identify potential side effects. As an Early Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants a chance to be among the first to experience this innovative approach.

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.

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

Research shows that treatments using carboplatin, paclitaxel, and cisplatin are generally well-tolerated. Studies have found that administering carboplatin every three weeks is a practical and relatively safe option. However, about 30% of patients may experience anemia, which means having fewer red blood cells, as a side effect.

For patients undergoing surgery combined with hyperthermic intraepithelial chemotherapy (HIPEC), studies suggest that using cisplatin and paclitaxel in this manner is safe and effective. This method circulates heated chemotherapy drugs in the abdomen during surgery and has been linked to better outcomes in treating advanced ovarian cancer.

Overall, these treatments have been used in various situations and are considered to have a manageable safety profile. While there are possible risks, as with any treatment, evidence suggests they are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for ovarian cancer because they incorporate a unique technique called Hyperthermic Intraperitoneal Chemotherapy (HIPEC). Unlike standard chemotherapy, which is administered intravenously, HIPEC delivers heated chemotherapy drugs directly into the abdominal cavity during surgery. This direct application allows for higher concentrations of the drug to target cancer cells more effectively while minimizing systemic side effects. The combination of HIPEC with cisplatin in this trial is particularly promising, as it could enhance the drug's ability to kill cancer cells and improve patient outcomes.

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

Research has shown that hyperthermic intraperitoneal chemotherapy (HIPEC) holds promise for ovarian cancer treatment. In this trial, some participants will receive HIPEC alongside surgery. One study found that patients who received HIPEC had an 83.3% chance of surviving for five years, which is very encouraging. HIPEC involves heating chemotherapy drugs, such as cisplatin, and circulating them in the abdomen during surgery. This process can enhance the drugs' effectiveness. The goal is to kill more cancer cells by using both heat and chemotherapy together. Early results suggest that combining HIPEC with surgery might better control cancer spread compared to traditional methods. ^{6 7 8 9 10}

Who Is on the Research Team?

Floor Backes, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Cytoreductive Surgery
• Hyperthermic Intraperitoneal Chemotherapy
• Paclitaxel

Trial Overview The 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.

How Is the Trial Designed?

Group I: Arm II (carboplatin, paclitaxel, CRS, HIPEC, cisplatin) Experimental Treatment 9 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 Treatment 8 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

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Published Research Related to This Trial

The maximum tolerated dose (MTD) of carboplatin for intraperitoneal hyperthermic chemotherapy (IPHC) was established at 1000 mg/m², as higher doses led to significant toxicity.

Patients who received IPHC at the MTD were able to complete standard systemic chemotherapy afterward, and repeat IPHC was safely performed during second look surgeries without severe toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal hyperthermic chemotherapy using carboplatin: a phase I analysis in ovarian carcinoma. Lentz, SS., Miller, BE., Kucera, GL., et al.[2013]

Two large trials showed that the combination of paclitaxel and cisplatin is more effective than cisplatin and cyclophosphamide in treating advanced ovarian cancer, leading to higher response rates and longer survival times.

The combination of carboplatin and paclitaxel has similar efficacy to cisplatin and paclitaxel but with reduced toxicity, making it the preferred treatment regimen for ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin in the treatment of ovarian cancer. Ozols, RF.[2015]

Combining hyperthermia with chemotherapy significantly reduces the lethal dose required to kill ovarian cancer cells, indicating a potentiated cytotoxic effect.

The study found that maintaining a temperature around 40 °C is optimal for enhancing the effectiveness of chemotherapy, while higher temperatures require increased drug concentrations to achieve similar results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxic effect of hyperthermia and chemotherapy with platinum salt on ovarian cancer cells: results of an in vitro study. Muller, M., Chérel, M., Dupré, PF., et al.[2013]

A prospective randomized trial showed that the combination of paclitaxel and cisplatin significantly improved response rates, time to progression, and median survival (37.5 months) compared to cisplatin plus cyclophosphamide (24.4 months) in patients with advanced ovarian cancer.

Paclitaxel combined with carboplatin has also been found to be effective in previously untreated patients, leading to the adoption of paclitaxel-based regimens as the new standard treatment for advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of chemotherapy for ovarian cancer. Ozols, RF.[2015]

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]

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 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]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

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]

A large meta-analysis involving over 2,000 patients showed that carboplatin is as effective as cisplatin for treating advanced ovarian cancer, but with significantly less toxicity, making it a safer option for patients.

The combination of carboplatin and cyclophosphamide is recognized as an effective therapy, and ongoing clinical trials are exploring various regimens to optimize treatment strategies for advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin versus cisplatin in ovarian cancer. Alberts, DS.[2015]

In a randomized phase III study involving 145 patients with untreated epithelial ovarian cancer, the carboplatin regimen was associated with lower rates of nausea, vomiting, and neurotoxicity compared to the cisplatin regimen.

However, the carboplatin regimen resulted in higher myelotoxicity, indicating a trade-off in side effects between the two treatment options, with cisplatin requiring hospital admission while carboplatin can be given to outpatients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (175 mg/m2 over 3 hours) with cisplatin or carboplatin in previously untreated ovarian cancer: an interim analysis. Neijt, JP., Engelholm, SA., Witteveen, PO., et al.[2015]

In a study of 96 patients with advanced ovarian cancer, intraperitoneal hyperthermic chemotherapy (IPHC) using paclitaxel showed a 5-year survival rate of 84.6%, significantly higher than the 32.8% survival rate in the control group receiving conventional therapy.

Both IPHC-paclitaxel and IPHC-carboplatin significantly reduced the risk of disease progression and death, indicating that these treatments could be effective options for improving outcomes in advanced ovarian cancer during secondary surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer with paclitaxel- or carboplatin-based intraperitoneal hyperthermic chemotherapy during secondary surgery. Bae, JH., Lee, JM., Ryu, KS., et al.[2015]

Citations

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Hyperthermic intraperitoneal chemotherapy with cisplatin ... The 5-year overall survival was 83.3%, although one patient died shortly after 5 years. Baratti [23] published a phase 2 study in 2016 that assessed adjuvant ...

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and mitomycin C-based hyperthermic intraperitoneal ... Our results demonstrated that oxaliplatin- and MMC-based HIPEC procedures are both temperature- and duration-dependent in an in vivo tumor model.

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Hyperthermic intraperitoneal chemotherapy using a ... Here we show the efficacy of the 3-drug combination of mitomycin C (MMC), 5-fluorouracil (5FU), and oxaliplatin (OHP) in an in vitro simulation of HIPEC.

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Efficacy and Safety of Intraoperative Hyperthermic ... This phase 3 randomized clinical trial assesses locoregional control rates after hyperthermic intraperitoneal chemotherapy with mitomycin C

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Hyperthermic intraperitoneal chemotherapy (HIPEC) for ... In this HIPEC the dose of oxaliplatin is reduced to 200 mg/m2. However, in order to maximally utilize heat and to maximally utilize the effects of chemotherapy ...

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Comparison of the Efficacy of Cisplatin/Paclitaxel Versus ... A study reported that 30% of individuals receiving carboplatin for advanced ovarian cancer experienced anemia as an adverse effect [36]. However ...

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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 ...

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A phase I study evaluating the safety and pharmacokinetics ... The combination of carboplatin given every 3 weeks at an AUC of 5 and 1-h weekly paclitaxel at 80 mg/m2 is a feasible and reasonably well-tolerated regimen and ...

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Survival outcome and perioperative complication related to ... This systematic review and meta-analysis suggests that NACT-IDS with carboplatin and paclitaxel does not negatively impact the survival of women with advanced ...

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Efficacy and Safety of First-line Single-Agent Carboplatin ... This randomized clinical trial compares the feasibility, efficacy, and safety of single-agent carboplatin every 3 weeks, ...