CytoreductiveSurgery & HIPEC w/Gemcitabine+Chemotherapy w/Dacarbazine in Uterine Leiomyosarcoma

Phase 2 Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) With Gemcitabine Followed by Systemic Adjuvant Chemotherapy With Dacarbazine for Locally Recurrent Uterine Leiomyosarcoma (LMS)

The purpose of this study is to find out if giving a dose of heated chemotherapy in the abdomen immediately after surgery that is done to remove uterine leiomyosarcoma type of cancer will help lower the risk of the cancer coming back in the future.

Study Overview

• Status: Recruiting
• Conditions: Uterine Leiomyosarcoma; LMS - Leiomyosarcoma
• Intervention / Treatment: Drug: Gemcitabine; Drug: Dacarbazine; Procedure: Cytoreductive Surgery; Behavioral: Functional Assessment of Cancer Therapy (FACT) G questionnaire; Procedure: Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) Scan; Drug: Gadolinium

Detailed Description

Primary Objective:

- To assess the efficacy of cytoreductive surgery with gemcitabine HIPEC followed by postoperative systemic chemotherapy with dacarbazine in subjects with locally recurrent uterine LMS.

Secondary Objectives:

• To assess the safety of cytoreductive surgery with gemcitabine HIPEC in subjects with locally recurrent uterine LMS.
• To assess the 6 month and 12 month intraabdominal relapse free survival in subjects with locally recurrent uterine LMS
• To determine quality of life prior to therapy (within 28 days prior to surgery with HIPEC), 4 to 6 weeks after surgery with HIPEC, and then at Cycle

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ghazal Jawed; Phone Number: 650-724-1388; Email: gjawed@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford University
      • Principal Investigator: Kristen N Ganjoo, MD
      • Contact: Ghazal Jawed; Phone Number: 650-724-1388; Email: gjawed@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed diagnosis of uterine leiomyosarcoma (LMS) with evidence of local recurrence.
2. Imaging provides evidence of locally recurrent uterine LMS.
3. Candidate for potentially radical, maximal effort cytoreductive surgery at the discretion and expertise of the treating physician.
4. Age ≥ 18 years.
5. Life expectancy > 3 months.
6. Women of childbearing potential (WOCBP) will have a negative pregnancy test ≤ 7 days prior to surgery (this test can be omitted if subject is post menopausal by either surgery or elevated FSH)
7. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
8. Hemoglobin (HGB) ≥ 9 g/dL.
9. White blood cell count (WBC) ≥ 3.0 K/ul.
10. Absolute neutrophil count (ANC) ≥ 1.5 K/ul.
11. Platelets (PLT) ≥ 100 K/ul.
12. Total bilirubin within normal institutional limits.
13. Serum glutamic oxaloacetic transaminase (SGOT/Serum glutamic pyruvic transaminase (SGPT) < 2.5 x institutional upper limit of normal (ULN).
14. Creatinine < 1.5 x ULN or creatinine clearance > 60 mL/min according to Cockroft Gault formula.
15. 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.
16. Serum albumin ≥ 2.5 g/dL.
17. Ability to understand and the willingness to personally sign the written IRB approved informed consent document.

Note that this study does not allow the use of a legally authorized representative

Exclusion Criteria:

1. Recurrence of LMS within less than 6 months after the last dose of gemcitabine.
2. Active extra abdominal disease including active malignant pleural effusion. Subjects who have been successfully treated with neoadjuvant chemotherapy and no longer have (malignant) pleural effusions may be included.
3. Prior gemcitabine given in non adjuvant setting.
4. Prior treatment with dacarbazine.
5. Active infection requiring antibiotics.
6. Unresolved toxic effects of prior therapy (except alopecia). Resolution is considered ≤ Grade 1 per NCI CTCAE, version 5.0.
7. Pregnant.
8. Breast feeding.
9. Presence of metastatic liver disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cytoreductive Surgery+HIPEC gemcitabine+dacarbazine; 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

Drug: Gemcitabine; Hyperthermic intraperitoneal chemotherapy (HIPEC) with gemcitabine. Gemcitabine will be instilled at a dose of 1000 mg/m2 for 60 minutes at temperatures of 42° to 43°C.; Other Names: Gemzar; difluorodeoxycytidine hydrochloride; Infugem; Drug: Dacarbazine; Dacarbazine 1000 mg/m2 IV every 3 weeks x 6 cycles given IV; Other Names: Biocarbazine; Dacarbazine - DTIC; Dimethyl (triazeno) imidazolecarboxamide; Procedure: Cytoreductive Surgery; Surgery for cancer removal; Behavioral: Functional Assessment of Cancer Therapy (FACT) G questionnaire; Preoperative and Postoperative FACT G questionnaire to assess QoL; Procedure: Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) Scan; Radiologic imaging after Cycle 3 and 6 and at each follow up visit; Drug: Gadolinium; Contrast Agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Progression free survival as measured from the time of surgery until death or disease progression.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Grade 4 infections	Rate of Grade 4 infections within 30 days post surgery with gemcitabine HIPEC will be assessed using CTCAE version 5.0.	30 days post surgery with gemcitabine HIPEC
Intraabdominal relapse free survival	Relapse free survival as measured from time of surgery until intraabdominal recurrence	6 months
Intraabdominal relapse free survival	Relapse free survival as measured from time of surgery until intraabdominal recurrence	12 months
Overall Functional Assessment of Cancer Therapy: General (FACT G) score	Difference in overall FACT G score from baseline to 4 to 6 weeks post-surgery with gemcitabine HIPEC. FACT G is a quality of life questionnaire composed of 27 items divided into four main quality of life categories: Physical Well Being (PWB); Social/Family Well Being (SWB); Emotional Well Being (EWB); and Functional Well Being (FWB). Total FACT G score is obtained by summing the scores from the four main QoL categories (PWB; SWB; EWB; FWB). The range of the scale is 0-108. Negatively worded items are reverse scored prior to summing so that higher subscale and total scores indicate better Quality of life (Qol).	Baseline, 4 to 6 weeks post-surgery with HIPEC

Collaborators and Investigators

• Sponsor: Kristen Ganjoo
• Investigators: Principal Investigator: Kristen N Ganjoo, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2021
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: January 22, 2021
• First Submitted That Met QC Criteria: January 22, 2021
• First Posted (Actual): January 27, 2021

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 3, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Muscle Tissue; Leiomyosarcoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Dacarbazine; Gemcitabine
• Other Study ID Numbers: IRB-56728; SARCOMA0045 (Other Identifier: OnCore); NCI-2021-03258 (Other Identifier: CTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No