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

Kristen Ganjoo

Status and phase: Enrolling; Phase 2

Conditions: LMS - Leiomyosarcoma; Uterine Leiomyosarcoma

Treatments: Behavioral: Functional Assessment of Cancer Therapy (FACT) G questionnaire; Drug: Gemcitabine; Procedure: Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) Scan; Drug: Gadolinium; Drug: Dacarbazine; Procedure: Cytoreductive Surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT04727242

SARCOMA0045 (Other Identifier)

IRB-56728

NCI-2021-03258 (Other Identifier)

Details and patient eligibility

About

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.

Full 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

Enrollment: 25 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

Cytoreductive Surgery+HIPEC gemcitabine+dacarbazine

Experimental group

Description:

* 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

Treatment:

Procedure: Cytoreductive Surgery

Drug: Dacarbazine

Drug: Gadolinium

Procedure: Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) Scan

Drug: Gemcitabine

Behavioral: Functional Assessment of Cancer Therapy (FACT) G questionnaire