Trisenox® in Women With Metastatic Endometrial Cancer

This study has been terminated.
(Accrual was very low. No subject had been enrolled in a year.)
Sponsor:
Collaborator:
Cephalon
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01184053
First received: July 22, 2010
Last updated: February 15, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Endometrial Carcinoma
Drug: Arsenic trioxide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Trisenox in Women With Recurrent or Metastatic Endometrial Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Objective response (CR+PR) rate of subjects given Trisenox [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Safety of Trisenox® [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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.

  • Progression free survival, and overall survival in patients treated with Trisenox® [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Progression-Free survival is the period from start of treatment until disease progression, death, or date of last contact.

  • Duration of response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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)

  • Associations between markers of angiogenesis (e.g. VEGF) with response [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 5
Study Start Date: February 2012
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Arsenic trioxide
    Arsenic trioxide - 0.25 mg/kg/day for 5 consecutive days, every 4 weeks.
    Other Name: Trisonex
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01184053

Locations
United States, North Carolina
North Carolina Cancer Hosptial, UNC
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Cephalon
Investigators
Principal Investigator: Paola Gehrig, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01184053     History of Changes
Other Study ID Numbers: LCCC 0920
Study First Received: July 22, 2010
Last Updated: February 15, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
endometrial
carcinoma
recurrent
metastatic
Trisenox
arsenic trioxide
Phase II
VEGF
gynecology
Lineberger
UNC

Additional relevant MeSH terms:
Carcinoma
Endometrial Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Arsenic trioxide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014