Trisenox® in Women With Metastatic Endometrial Cancer (NRR)

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

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.

Study Overview

• Status: Terminated
• Conditions: Endometrial Carcinoma
• Intervention / Treatment: Drug: Arsenic trioxide

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • North Carolina Cancer Hosptial, UNC

Participation Criteria

Eligibility Criteria

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

Description

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. Eastern Cooperative Oncology Group (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 corrected QT interval (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

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: Trisenox treatment; Arsenic trioxide - 0.25 mg/kg/day for 5 consecutive days, every 4 weeks.	Drug: Arsenic trioxide; Arsenic trioxide - 0.25 mg/kg/day for 5 consecutive days, every 4 weeks.; Other Names: Trisenox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response (CR+PR) Rate of Subjects Given Trisenox	To estimate the objective response (CR+PR) rate (as defined by the Gynecologic Oncology Group [GOG] RECIST Criteria)of Trisenox® in women with recurrent or metastatic endometrial cancer when administered at 0.25 mg/kg/day for 5 consecutive days (D1-5) every 4 weeks.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		5 years
Progression Free Survival in Patients Treated With Trisenox®	Progression-Free survival is the period from start of treatment until disease progression, death, or date of last contact.	28 days
Associations Between Markers of Angiogenesis (e.g. VEGF) With Response	We will request a blood sample to measure vascular endothelial growth factor (VEGF) as well as other angiogenic factors and correlate levels to response to arsenic trioxide. Such effects have been observed in cultured cell lines and animal models, as well as clinical studies.	4 years

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: Cephalon
• Investigators: Principal Investigator: Paola Gehrig, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• web address for Lineberger Comprehensive Cancer Center, UNC
• web address for the National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: July 22, 2010
• First Submitted That Met QC Criteria: August 17, 2010
• First Posted (Estimate): August 18, 2010

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: May 16, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: carcinoma; VEGF; metastatic; Phase II; gynecology; recurrent; endometrial; Trisenox; Lineberger; UNC; vascular endothelial growth factor; University of North Carolina at Chapel Hill; arsenic trioxide
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms; Antineoplastic Agents; Arsenic Trioxide
• Other Study ID Numbers: LCCC 0920

Plan for Individual participant data (IPD)

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