Trisenox� in Women With Metastatic Endometrial Cancer

Condition(s) targeted: Endometrial Carcinoma

Intervention: Arsenic trioxide (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: UNC Lineberger Comprehensive Cancer Center

Official(s) and/or principal investigator(s):
Paola Gehrig, MD, Principal Investigator, Affiliation: UNC Lineberger Comprehensive Cancer Center

Overall contact:
Donna Rowe, RN, Phone: (919) 966-4432, Email: donna_rowe@med.unc.edu

The primary purpose of this study is to see whether women who have already received chemotherapy for their endometrial cancer, or who have disease that has spread outside of the uterus, will respond to the drug arsenic trioxide (Trisenox®) as judged by shrinkage of their tumor.

Official title: A Phase II Trial of Trisenox in Women With Recurrent or Metastatic Endometrial Adenocarcinoma

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Objective response (CR+PR) rate of subjects given Trisenox

Secondary outcome:

Safety of Trisenox®

Progression free survival, and overall survival in patients treated with Trisenox®

Duration of response

Associations between markers of angiogenesis (e.g. VEGF) with response

Detailed description: This is an open-label, single arm, single institution, phase II trial designed to assess the response rate and safety of Trisenox® in women with recurrent endometrial carcinoma. Trisenox® will be administered at a dose of 0. 25 mg/kg/day for 5 consecutive days (D1-5) every 4 weeks. A 4-week period will be defined as a cycle of treatment. Marker and non-marker lesions will be assessed every 2 cycles (every 8 weeks) and the response assigned according to Gynecologic Oncology Group (GOG) RECIST guidelines. Safety will be assessed by routine physical, laboratory and ECG evaluations. Up to 10 patients will be enrolled into the study. Patients are expected (excluding any unforeseen toxicities) to receive a minimum of 2 and a maximum of 6 cycles of Trisenox®. (Patients with at least documented stable disease may be eligible for >6 cycles). Patients will be followed for 6 months after their last dose of Trisenox®.

For this trial we would allow one prior cytotoxic regimen since the time of recurrence and patients may have had one prior regimen as part of their induction chemotherapy. Patients will be treated with 0. 25 mg/kg/day for days 1-5 every 28 days and patients may remain on trial until progression of disease.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

Inclusion Criteria:

1. ≥18 years of age with histologically confirmed metastatic or recurrent endometrial cancer

2. Documented progression of their endometrial cancer (i. e., within the last 3 months)

3. If of childbearing potential they must agree to use approved barrier methods of contraception

4. Presence of at least one measurable lesion that:

- Can be accurately measured in at least one dimension with longest diameter ≥20

mm using conventional techniques or ≥10 mm with spiral CT scan (or otherwise at least twice the reconstruction interval for CT or MRI scans).

- Previously irradiated lesions may be considered to be measurable provided: 1)

there has been documented progression of the lesion(s) since completion of radiotherapy, and 2) the criteria for measurability as outlined above are met.

5. ECOG performance status ≤ 2

6. Minimum life expectancy of 3 months

7. Adequate renal and hepatic function (per study protocol guidelines)

8. Adequate bone marrow function (per study protocol guidelines)

9. Serum cholesterol <350 mg/dL and triglycerides < 400 mg/dL

10. Able to understand and give written informed consent

11. Ejection fraction >55% with no focal left ventricular wall motion abnormalities in patients with a history of coronary artery disease or a history of congestive heart failure.

Exclusion Criteria:

1. Women who are pregnant or lactating

2. Presence of brain metastases

3. Two or more prior cycles of cytotoxic chemotherapy since recurrence (Two total regimens are allowed if one includes adjuvant therapy.)

4. Prior therapy with Trisenox or known sensitivity to this agent

5. Prior anticancer treatment (chemotherapy, radiotherapy, immunotherapy, biological response modifiers, signal transduction inhibitors, etc) within 4 weeks prior to the first dose of Trisenox.

6. Ongoing toxicity associated with prior anticancer therapy (except peripheral neuropathy of ≤ grade 1 by NCI toxicity criteria)

7. Another primary malignancy within the past three years (except for non-melanoma skin cancer and cervical carcinoma in situ)

8. Significant uncontrolled cardiovascular disease

9. Active infection requiring systemic therapy

10. Known HIV infection

11. Treatment with any investigational agent within 4 weeks prior to the first dose of Trisenox

12. Concurrent treatment with immunosuppressive agents other than prescribed corticosteroids

13. Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 2 weeks prior to the first dose of Trisenox

14. Patients having undergone recent placement of a central venous access port will be considered eligible if they have recovered

15. Presence of any other life-threatening illness or organ system dysfunction which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluating the safety of the study drug

16. Prolonged absolute QTc interval > 500 msec

17. Underlying conduction disease that prevents measurement of QT interval

18. History of ventricular tachycardia or any cardiac arrhythmia requiring the placement of an automated intraventricular cardiac defibrillator.

19. Inability to discontinue therapy with class I or class III antiarrhythmic medications.

20. Inability to discontinue drugs known to be associated with a risk for torsades de pointes

Donna Rowe, RN, Phone: (919) 966-4432, Email: donna_rowe@med.unc.edu

North Carolina Cancer Hosptial, UNC, Chapel Hill, North Carolina 27599, United States; Recruiting
Paola Gehrig, MD, Principal Investigator

web address for Lineberger Comprehensive Cancer Center, UNC

web address for the National Cancer Institute (NCI)

Starting date: February 2010
Last updated: July 6, 2011