Trisenox® in Women With Metastatic Endometrial Cancer

Endometrial Carcinoma Clinical Trial

— NRR  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01184053
• Other study ID #: LCCC 0920
• Status: Terminated
• Phase: Phase 2
• First received: July 22, 2010
• Last updated: January 20, 2016
• Start date: March 2010
• Est. completion date: March 2012

Study information

• Verified date: January 2016
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endometrial Carcinoma
• Endometrial Neoplasms

Intervention

Drug:
• Arsenic trioxide
Arsenic trioxide - 0.25 mg/kg/day for 5 consecutive days, every 4 weeks.

Locations

Country	Name	City	State
United States	North Carolina Cancer Hosptial, UNC	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	Cephalon

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 years	No
Secondary	Safety of Trisenox®	Any patient who receives at least one dose of Trisenox® on this protocol will be evaluable for toxicity. Safety will be assessed by routine physical, laboratory and ECG evaluations. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting.	2 years	Yes
Secondary	Progression free survival, and overall 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.	2 years	No
Secondary	Duration of response	Patients will have target lesions assessed. These lesions will be identified and will be re-evaluated every even cycle (cycle 2, cycle 4, cycle 6, etc)	2 years	No
Secondary	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	No

External Links

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