Surgery + Chemotherapy for Ovarian Cancer

Recruiting at 3 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Disqualifiers: Extra-abdominal disease, Cardiac, Pulmonary, others

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

Compensation: Varies

Number of Visits: 4

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and how well surgery and heated chemotherapy with or without non-heated chemotherapy after surgery works in treating patients with ovarian, fallopian tube, uterine, or peritoneal cancer. Giving a dose of heated chemotherapy into the abdomen during surgery that is done to remove ovarian, fallopian tube, uterine, or peritoneal cancer may help lower the risk of the cancer coming back. Giving unheated chemotherapy drugs directly into the abdomen after surgery may kill more tumor cells.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on neoadjuvant chemotherapy, it must be stopped at least 3 weeks before surgery.

What evidence supports the effectiveness of the drug combination used in the clinical trial for ovarian cancer?

Research shows that combining paclitaxel with platinum-based drugs like cisplatin or carboplatin is effective for treating advanced ovarian cancer, leading to higher response rates and longer survival times compared to older treatments. Paclitaxel and carboplatin together have been found to be as effective as paclitaxel and cisplatin, but with less toxicity, making it a preferred regimen. ^{1 2 3 4 5}

Is the combination of surgery and chemotherapy safe for treating ovarian cancer?

The combination of surgery and chemotherapy, including drugs like carboplatin and paclitaxel, is generally considered safe for treating ovarian cancer, though it can cause side effects like neutropenia (low white blood cell count), neurotoxicity (nerve damage), and hypersensitivity reactions. These treatments are usually well-tolerated, but they are associated with significant toxicities, so they are best suited for patients who are in good health. ^{1 3 6 7 8}

How is the treatment of surgery plus chemotherapy for ovarian cancer different from other treatments?

This treatment combines surgery with chemotherapy using a mix of drugs like carboplatin, cisplatin, gemcitabine, and paclitaxel, which are known to be effective in treating ovarian cancer. The unique aspect is the combination of these specific drugs, which are being tested for their effectiveness in patients who may not respond to standard treatments, and the use of paclitaxel, which has shown promise in overcoming resistance to platinum-based drugs. ^{1 2 6 9 10}

Research Team

Thanh Dellinger

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for patients with stage III or IV ovarian, fallopian tube, uterine, or peritoneal cancer that's confined to the abdominal cavity. It includes those who've had neoadjuvant chemotherapy and surgery. Participants must be in good physical condition (ECOG <=1 or KPS >=70%), respond well to platinum-based treatments, have no active infections requiring antibiotics, and not be pregnant. They should also have adequate organ function and blood counts.

Inclusion Criteria

Provided informed consent

You have advanced or recurrent ovarian, fallopian tube, peritoneal, or uterine cancer that has spread within the abdomen.

You may need to have a major surgery to remove cancer, and your doctor thinks it's a good idea.

Exclusion Criteria

You have cancer in areas outside of the abdomen, such as in the chest with fluid buildup around the lungs. If you had this before but it's no longer there after treatment, you may still be able to join the study.

Pregnant, nursing, or of childbearing potential and refuse hysterectomy or bilateral salpingo-oophorectomy

Your surgery did not remove all of the unhealthy tissue.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and HIPEC Treatment

Patients undergo surgery and receive hyperthermic cisplatin intraperitoneally over 60 minutes

1 day

1 visit (in-person)

Postoperative Chemotherapy

Beginning at least 3 weeks after surgery, patients may receive additional chemotherapy (carboplatin, paclitaxel, pegylated liposomal doxorubicin hydrochloride, or gemcitabine hydrochloride) intraperitoneally or intravenously

Variable, based on treatment plan

Follow-up

Patients are monitored for safety and effectiveness after treatment

Up to 3 years

Follow-up visits at 3-6, 6-9, 9-12, and 12-15 months; every 3 months for 1 year; and then every 4 months for 1 year

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Gemcitabine Hydrochloride
• Paclitaxel
• Pegylated Liposomal Doxorubicin Hydrochloride
• Therapeutic Conventional Surgery

Trial Overview The study tests how effective heated chemotherapy during surgery is compared to adding non-heated chemo after surgery for certain cancers. The goal is to see if heated chemo can better prevent cancer from returning by killing more tumor cells when applied directly into the abdomen during surgical removal of the cancer.

Participant Groups

Group I: Treatment (surgery, HIPEC cisplatin) Experimental Treatment 8 Interventions

Patients undergo surgery and receive hyperthermic cisplatin IP over 60 minutes. Beginning at least 3 weeks after surgery, patients may receive carboplatin, paclitaxel, pegylated liposomal doxorubicin hydrochloride, or gemcitabine hydrochloride IP or IV at the discretion of the medical and gynecologic oncologists.

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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

Paclitaxel has been established as an effective treatment for newly diagnosed ovarian cancer patients, leading to its incorporation into primary chemotherapy regimens, particularly in combination with cisplatin as the new standard in the U.S.

Ongoing clinical trials are exploring various strategies to optimize paclitaxel-based chemotherapy, including comparisons of different platinum-based drugs and infusion schedules, as well as evaluating high-dose therapies with stem cell support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of advanced ovarian cancer: current status and future directions. Ozols, RF., Vermorken, JB.[2015]

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]

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 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]

The combination of carboplatin and 3-hour infusional paclitaxel was well-tolerated in a study of 92 women with advanced gynecologic cancers, showing a manageable toxicity profile with neutropenia being the most significant side effect.

In patients with ovarian cancer or primary peritoneal carcinoma, 74% experienced a significant decline in tumor marker levels after treatment, indicating strong antineoplastic activity of this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin plus paclitaxel in the treatment of gynecologic malignancies: the Cleveland Clinic experience. Markman, M., Kennedy, A., Webster, K., et al.[2015]

Combination chemotherapy is more effective than single-agent therapy for recurrent ovarian cancer, indicating a need for multi-drug approaches in treatment.

While intraperitoneal drug administration has shown improved survival in patients with small-volume stage III disease, it comes with significant toxicity, highlighting the need to balance efficacy and safety in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges for chemotherapy in ovarian cancer. Ozols, RF.[2020]

References

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

Treatment of ovarian cancer: current status. [2015]

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

Chemotherapy of advanced ovarian cancer: current status and future directions. [2015]

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

Taxane/platinum/anthracycline combination therapy in advanced epithelial ovarian cancer. [2015]

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

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

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

Current status of chemotherapy for ovarian cancer. [2015]

6. 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]

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

Carboplatin plus paclitaxel in the treatment of gynecologic malignancies: the Cleveland Clinic experience. [2015]

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

Taxol in epithelial ovarian cancer. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Challenges for chemotherapy in ovarian cancer. [2020]

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

Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. [2022]