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

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses heated chemotherapy in the abdomen to treat patients with recurring uterine cancer. The heat helps the drug work better, and additional medication is given to target any remaining cancer 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 a stable dose of therapeutic warfarin or low molecular weight heparin, you may continue as long as your INR is in range.

Is Surgery + HIPEC with Chemotherapy generally safe for humans?

Research shows that Surgery + HIPEC (a heated chemotherapy treatment applied directly to the abdomen) is generally safe for humans, with studies indicating no increase in serious complications for conditions like ovarian cancer and pseudomyxoma peritonei (a rare abdominal cancer). ^{1 2 3 4 5}

What makes the treatment of Surgery + HIPEC with Chemotherapy for Uterine Cancer unique?

This treatment is unique because it combines surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), where chemotherapy is heated and applied directly inside the abdomen to target cancer cells more effectively. This approach is promising for aggressive uterine cancer, potentially improving survival and reducing recurrence compared to standard treatments. ^{1 2 4 6 7}

Research Team

Kristen N Ganjoo, MD

Principal Investigator

Stanford University

Eligibility Criteria

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

I am 18 years old or older.

Hemoglobin (HGB) ≥ 9 g/dL

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Hyperthermic intraperitoneal chemotherapy in interval debulking surgery for advanced epithelial ovarian cancer: A single-center, real-life experience. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of hyperthermic intraperitoneal chemotherapy and interval debulking surgery in women with advanced uterine serous carcinoma. [2022]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Incorporation of paclitaxel-based hyperthermic intraperitoneal chemotherapy in patients with advanced-stage ovarian cancer treated with neoadjuvant chemotherapy followed by interval debulking surgery: a protocol-based pilot study. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Perioperative safety after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei from appendiceal origin: Experience on 254 patients from a single center. [2020]

5. Switzerland 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. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The Role of Hyperthermic Intraperitoneal Chemotherapy in Uterine Cancer Therapy. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Impact of surgical and clinical factors on the pharmacology of intraperitoneal doxorubicin in 145 patients with peritoneal carcinomatosis. [2013]