Surgery + HIPEC with Chemotherapy for Uterine Cancer

Overseen By Kristen Ganjoo, M.D.

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Gemcitabine, Dacarbazine

Disqualifiers: Active infection, Metastatic liver disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether administering a heated dose of chemotherapy directly into the abdomen immediately after surgery can help prevent the recurrence of uterine leiomyosarcoma, a type of uterine cancer. The treatment involves cytoreductive surgery to remove as much cancer as possible, followed by heated chemotherapy with gemcitabine, and additional chemotherapy with dacarbazine. Women with a confirmed diagnosis of recurrent uterine leiomyosarcoma who can undergo major surgery might be suitable candidates for this study. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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 a stable dose of therapeutic warfarin or low molecular weight heparin, you may continue as long as your INR is in range.

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

Research has shown that a treatment plan involving surgery to remove as much cancer as possible, followed by heated chemotherapy with gemcitabine and additional treatment with dacarbazine, is safe. Early study results suggest that patients tolerate this treatment well, with no major safety issues reported.

The surgery aims to remove as much cancer as possible. Heated chemotherapy is then applied directly to the abdomen to target any remaining cancer cells. Finally, patients receive dacarbazine, a chemotherapy drug, to help prevent the cancer from returning.

Studies indicate that this combination of treatments does not cause unexpected side effects and appears promising for people with recurrent uterine sarcoma, a type of cancer that starts in the uterus. The goal is to manage the disease with minimal risk. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of cytoreductive surgery with HIPEC and systemic chemotherapy using dacarbazine for treating uterine cancer because it offers a novel approach that could enhance treatment effectiveness. Unlike standard treatments, which typically involve surgery followed by regular chemotherapy, this method uses hyperthermic intraperitoneal chemotherapy (HIPEC) with gemcitabine. HIPEC involves directly washing the abdominal cavity with heated chemotherapy, potentially targeting cancer cells more effectively. Additionally, the use of dacarbazine as postoperative systemic chemotherapy might offer a new therapeutic option, aiming to reduce recurrence rates and improve patient outcomes. This innovative combination is being studied to determine if it can provide better results than existing treatments.

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

This trial will evaluate the combination of cytoreductive surgery and a special heated chemotherapy treatment called HIPEC, using the drug gemcitabine, followed by postoperative systemic chemotherapy with dacarbazine. Studies have shown that HIPEC with gemcitabine can benefit patients with certain cancers, such as uterine sarcoma. Specifically, patients who received HIPEC lived an average of 43.8 months, compared to 35.9 months for those who underwent regular surgery. Early results suggest this treatment is safe and feasible for individuals with cancer spread in the abdomen from uterine sarcoma. Additionally, using dacarbazine after surgery has been found to be safe. These findings support the potential of this treatment to reduce the risk of cancer recurrence. ^{1 2 3 4 5}

Who Is on the Research Team?

Kristen N Ganjoo, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults with confirmed uterine leiomyosarcoma who are candidates for aggressive surgery to remove the cancer. They must have a certain level of blood cells, liver and kidney function, and be able to sign consent. Pregnant or breastfeeding women, those with active infections or unresolved treatment side effects (except hair loss), prior non-adjuvant gemcitabine use, recent recurrence after gemcitabine, metastatic liver disease, or active extra abdominal disease cannot join.

Inclusion Criteria

Prothrombin Time (PT) such that international normalized ratio (INR) is < 1.5 (or an in range INR, usually between 2 and 3, if a subject is on a stable dose of therapeutic warfarin or low molecular weight heparin) and a partial thromboplastin time (PTT) < 1.2 times control

Hemoglobin (HGB) ≥ 9 g/dL

My uterine cancer has come back after treatment.

Exclusion Criteria

You are currently breastfeeding.

My cancer has spread to my liver.

My LMS came back within 6 months after my last gemcitabine dose.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cytoreductive Surgery and HIPEC

Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with gemcitabine

1 day

1 visit (in-person)

Postoperative Systemic Chemotherapy

Systemic adjuvant chemotherapy with dacarbazine starting 30 days post-surgery

18 weeks

6 visits (in-person, every 3 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Cytoreductive Surgery
• Dacarbazine
• Gemcitabine

Trial Overview The study tests if heated chemotherapy given in the abdomen right after surgery can prevent uterine leiomyosarcoma from returning. Participants undergo cytoreductive surgery followed by HIPEC with Gemcitabine plus Dacarbazine chemotherapy. Their condition is monitored using FACT G questionnaires and imaging scans like CT or MRI with Gadolinium contrast.

How Is the Trial Designed?

Group I: Cytoreductive Surgery+HIPEC gemcitabine+dacarbazine Experimental Treatment 6 Interventions

* Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with gemcitabine followed by postoperative systemic chemotherapy with dacarbazine. Conceptually, HIPEC will be administered as a 60 minute heated intraperitoneal infusion (ie, intraperitoneal "wash" or "lavage"). * HIPEC: Gemcitabine will be instilled at a dose of 1000 mg/m2 for 60 minutes at temperatures of 42° to 43°C. * Systemic adjuvant chemotherapy starting 30 days ± 14 days post surgery. Dacarbazine 1000 mg/m2 IV every 3 weeks x 6 cycles

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Kristen Ganjoo

Lead Sponsor

Trials

3

Recruited

80+

Published Research Related to This Trial

In patients with advanced epithelial ovarian cancer who underwent interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT), the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) significantly improved both progression-free survival (PFS) by 4.68 months and overall survival (OS) by 11.81 months compared to surgery alone, based on a review of 14 studies involving 1813 women.

However, in primary debulking surgery (PDS) and recurrent ovarian cancer (ROC), HIPEC did not show significant benefits in PFS or OS, and there was a slight increase in the risk of severe post-operative complications with the combined approach, indicating that while HIPEC can be beneficial in certain contexts, its role in other settings remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperthermic Intraperitoneal Chemotherapy (HIPEC): New Approaches and Controversies on the Treatment of Advanced Epithelial Ovarian Cancer-Systematic Review and Meta-Analysis. Della Corte, L., Conte, C., Palumbo, M., et al.[2023]

In a study of 145 patients with colorectal or appendiceal cancer, intraperitoneal doxorubicin showed significantly higher exposure to peritoneal surfaces (78 times greater) compared to plasma, indicating effective localized delivery of the drug.

Surgical factors, such as the extent of visceral resection and the size of the peritoneal space, significantly influenced doxorubicin clearance, suggesting that these factors should be considered when designing chemotherapy regimens for optimal efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of surgical and clinical factors on the pharmacology of intraperitoneal doxorubicin in 145 patients with peritoneal carcinomatosis. Sugarbaker, PH., Van der Speeten, K., Anthony Stuart, O., et al.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04727242

Study Details | NCT04727242 | CytoreductiveSurgery & ... Primary Objective: - To assess the efficacy of cytoreductive surgery with gemcitabine HIPEC followed by postoperative systemic chemotherapy with dacarbazine in ...

2. esmoopen.com esmoopen.com/article/S2059-7029(24)00321-1/fulltext

14MO Safety of cytoreductive surgery with hyperthermic ... Preliminary results of our phase II trial suggest that CRS/HIPEC with gemcitabine and adjuvant dacarbazine is safe. Further patient accrual and analysis are ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5986004/

Cytoreductive surgery and hyperthermic intraperitoneal ... We show that CRS/HIPEC is safe, feasible, and may benefit selected patients with peritoneal sarcomatosis from uterine sarcoma.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24074449

Efficacy of Hyperthermic Intraperitoneal Chemotherapy and ... Median overall survival was 35.9 months for patients treated with conventional surgery and 43.8 months for patients treated with HIPEC. Conclusions: Our study ...

5. cme.cityofhope.org cme.cityofhope.org/sites/default/files/media/2022-10/ISSPP%20PPT%20Template_Beatrice%20Sun.pdf

Safety of Cytoreductive Surgery with Heated Intraperitoneal ... Gemcitabine and Systemic Dacarbazine for Recurrent Uterine. Leiomyosarcoma ... ▫ CRS and HIPEC with Gemcitabine appears safe. ▫ Study has not met ...