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

Trial Summary

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. ^{1 2 3 4 5}

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. ^{2 3 4 6 7}

What makes hyperthermic intraperitoneal chemotherapy unique for ovarian cancer treatment?

Hyperthermic intraperitoneal chemotherapy (HIPEC) is unique because it involves heating chemotherapy drugs like carboplatin and cisplatin and delivering them directly into the abdominal cavity during surgery, which can enhance their effectiveness against ovarian cancer cells. ^{8 9 10 11 12}

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.

Research Team

Floor Backes, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

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.

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

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
• 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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

References

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

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

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

Treatment of ovarian cancer: current status. [2015]

3. England 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. [2020]

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

Carboplatin versus cisplatin in ovarian cancer. [2015]

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

Current status of chemotherapy for ovarian cancer. [2015]

6. Ireland pubmed.ncbi.nlm.nih.gov

The feasibility of carboplatin-based intraperitoneal chemotherapy in ovarian cancer. [2022]

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

Paclitaxel (175 mg/m2 over 3 hours) with cisplatin or carboplatin in previously untreated ovarian cancer: an interim analysis. [2015]

8. 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]

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

Intraperitoneal hyperthermic chemotherapy using carboplatin: a phase I analysis in ovarian carcinoma. [2013]

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

Treatment of ovarian cancer with paclitaxel- or carboplatin-based intraperitoneal hyperthermic chemotherapy during secondary surgery. [2015]

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

Hyperthermic intraperitoneal chemotherapy with carboplatin for optimally-cytoreduced, recurrent, platinum-sensitive ovarian carcinoma: a pilot study. [2013]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Cytotoxic effect of hyperthermia and chemotherapy with platinum salt on ovarian cancer cells: results of an in vitro study. [2013]