Surgery + Chemotherapy for Ovarian Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how surgery combined with heated chemotherapy, and possibly additional unheated chemotherapy, can treat ovarian, fallopian tube, uterine, or peritoneal cancer. The researchers aim to determine if heating the chemotherapy during surgery can reduce the chance of cancer returning and assess its safety and effectiveness. This trial suits individuals with advanced or recurring cancer confined to the abdomen who might benefit from surgery to remove most of the cancer. Participants should have shown some response to previous chemotherapy, such as a drop in tumor markers or reduced tumor size. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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.

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

Research shows that the treatments in this trial have been studied before and exhibit varying levels of safety.

Studies suggest that hyperthermic cisplatin, which involves heating the drug and delivering it into the abdomen, is becoming a standard treatment for advanced ovarian cancer and is generally well-tolerated.

Carboplatin, another chemotherapy drug used for ovarian cancer, can cause side effects like mild numbness or tingling in the hands and feet, but this occurs in a small percentage of patients.

Paclitaxel is also widely used in cancer treatments and has a safety profile that doctors can manage, allowing them to handle any side effects that arise.

Some studies note that pegylated liposomal doxorubicin, a type of chemotherapy with a protective coating, does not cause hair loss or heart problems, suggesting it is fairly safe.

Gemcitabine is considered well-tolerated, with ongoing studies combining it with other drugs for ovarian cancer showing promising safety results.

Overall, these treatments have been studied for safety in various settings, and while side effects can occur, they are often manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of surgery and chemotherapy for ovarian cancer because it includes a unique approach called hyperthermic intraperitoneal chemotherapy (HIPEC). This method involves directly applying heated cisplatin into the abdominal cavity during surgery, which may enhance the drug's effectiveness against cancer cells while minimizing systemic exposure. Additionally, the flexibility in post-surgery chemotherapy options allows treatment to be tailored to the patient's needs, potentially improving outcomes. This innovative use of localized, heated chemotherapy represents a promising advancement over traditional systemic treatments.

What evidence suggests that surgery and chemotherapy might be an effective treatment for ovarian cancer?

In this trial, participants will undergo surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin. Studies have shown that HIPEC with cisplatin, administered after surgery, can improve outcomes for ovarian cancer patients, extending overall survival to about 46 months and delaying cancer progression to 14.2 months. After surgery, participants may also receive additional chemotherapy options, including carboplatin, which significantly enhances survival, and paclitaxel, which is particularly effective when combined with carboplatin. Gemcitabine and pegylated liposomal doxorubicin are also beneficial, especially for recurrent or hard-to-treat ovarian cancer. These treatments effectively kill cancer cells, improving patient outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Thanh Dellinger

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8063137/

Efficacy and Safety of First-line Single-Agent Carboplatin ... At the data cutoff date, 76 patients (63%) had died, most (56 of 76 [74%]) from ovarian cancer. Median OS was not reached (95% CI, 21.0-32.2 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2667005424000255

Efficacy and safety of paclitaxel liposome versus ... The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of paclitaxel and carboplatin regarding therapeutic efficacy.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1505067

Weekly vs. Every-3-Week Paclitaxel and Carboplatin for ... In conclusion, our data suggest that weekly paclitaxel did not prolong progression-free survival, as compared with paclitaxel administered every ...

4. academic.oup.com academic.oup.com/jnci/article/96/22/1682/2521076

Phase III Randomized Trial of Docetaxel–Carboplatin Versus ... Results: After a median follow-up of 23 months, both groups had similar progression-free survival (medians of 15.0 months for docetaxel–carboplatin and 14.8 ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)31482-4/fulltext

First line chemotherapy with carboplatin plus paclitaxel in ... Only about 4% of patients received more than 6 courses without difference between treatment arms and only 8 patients switched from cisplatin to carboplatin due ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/carboplatin-intravenous-route/description/drg-20062578

Carboplatin (intravenous route) - Side effects & uses Carboplatin is used in combination with other cancer medicines to treat advanced ovarian cancer. It is also used alone to treat ovarian cancer ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4683379/

Limitations to the use of carboplatin-based therapy in ... The safety data from OVA-301 show that trabectedin + PLD can be considered as a treatment option at any relapse of ovarian cancer, including fully platinum- ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2004/20452scs001_paraplatin_lbl.pdf

PARAPLATIN (carboplatin aqueous solution) INJECTION ... *Use with Cyclophosphamide for Initial Treatment of Ovarian Cancer: Data are based on the experience of 393 patients with ovarian cancer (regardless of baseline.

9. labeling.pfizer.com labeling.pfizer.com/showlabeling.aspx?id=4379

carboplatin injection, solution Hospira, Inc. Peripheral neuropathies have been observed in 4% of the patients receiving carboplatin (6% of pretreated ovarian cancer patients) with mild paresthesias ...

10. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2778657

Efficacy and Safety of First-line Single-Agent Carboplatin ... At the data cutoff date, 76 patients (63%) had died, most (56 of 76 [74%]) from ovarian cancer. Median OS was not reached (95% CI, 21.0-32.2 ...