Endothelial Progenitor Cells in Cervical Cancer Patients Receiving Chemoradiation (EPC)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2008 by Mackay Memorial Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
National Science Council, Taiwan
Information provided by:
Mackay Memorial Hospital
ClinicalTrials.gov Identifier:
NCT00753610
First received: September 15, 2008
Last updated: NA
Last verified: September 2008
History: No changes posted
  Purpose

Invasive carcinoma of the uterine cervix remains the most common invasive cancer in women in many countries. Concurrent chemoradiotherapy (CCRT) is now recommended as a standard treatment for locally advanced and high-risk cervical carcinoma. However, CCRT achieves a better control of cervical cancer accompanied by greater morbidity. To avoid unnecessary over-treatment, the optimization of CCRT is of critical importance. Herein, the development of a surrogate marker for monitoring treatment efficacy as well as toxicity is pivotal to optimize CCRT.

Circulating endothelial progenitor cells (EPC), derived from bone marrow, can be used as a marker for optimizing and monitoring the anti-angiogenesis therapy including angiogenesis inhibitors and metronomic chemotherapy. Preclinical models indicated that the source of apoptotic circulating endothelial cells (CEC) was most likely the tumor vasculature. In breast cancer patients, apoptotic CEC were demonstrated to be a surrogate marker for efficacy of metronomic therapy.

In this grant, we intent to monitor the levels of circulating EPC/CEC in locally advanced cervical cancer patients before, during and after CCRT.


Condition
Cervical Cancer

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Effect of Concurrent Chemoradiation on Circulating Endothelial Progenitor Cells in Cervical Cancer

Resource links provided by NLM:


Further study details as provided by Mackay Memorial Hospital:

Estimated Enrollment: 30
Study Start Date: January 2007
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Detailed Description:

Invasive carcinoma of the uterine cervix remains the most common invasive cancer in women in many countries. Concurrent chemoradiotherapy (CCRT) is now recommended as a standard treatment for locally advanced and high-risk cervical carcinoma (1-3). Although the local control rate and survival have improved with use of CCRT, the treatment does cause greater toxicity in the bone marrow and other normal tissues compared with that caused by conventional RT. Our previous study demonstrated that serial changes in serum cytokines during chemoradiation correlated with tumor regression and treatment morbidity. The sudden elevation of serum TGF-beta 1 and VEGF levels after the first fraction of brachytherapy correlate with the development of greater RT morbidity. Higher pretreatment TGF-beta 1 and VEGF levels are associated with poor tumor response to chemoradiation (4). It implicates that angiogenic factor, such as VEGF, may play roles in the toxicity and outcome of CCRT. However, it still lacks a surrogate marker for prediction of clinical outcome of CCRT.

The most commonly used chemotherapeutic drugs combined with radiation as radiosensitizers are cis-platinum and 5-fluorouracil. These drugs, especially cis-platinum, are toxic to kidney, myelosuppressive and prone to cause life-threatening neutropenia, anemia or thrombocytopenia, which are more severe than those with radiotherapy alone (1-3). To avoid unnecessary over-treatment, the optimization of CCRT is of critical importance. Herein, the development of a surrogate marker for monitoring treatment efficacy as well as toxicity is pivotal to optimize CCRT.

Angiogenesis is a heavily regulated process, which is involved by complex interactions between inhibitory and stimulatory angiogenic factors. It is essential for tumor growth, progression and metastasis and is correlated with poor prognosis in cancer patients including cervical cancer (5). Many novel compounds, such as EGCG (6), that potently inhibit formation of neoplastic blood vessels have been recently developed. There is increasing interest in developing angiogeneis-suppressive agents for cancer treatment and growing number of anti-angiogenesis drugs currently being evaluated in clinical trials for various malignancies. Promising results have been reported include an increase in overall survival and reduction in the risk of death (Bevacizumab), reversal of cellular drug resistance (Cetuximab) and activity as second-line therapy in colorectal cancer patients who have exhausted other available treatment options (Cetuximab, ABX-EGF, PTK-787, Gefitinib, Erlotinib) (7,8).

Although the therapeutic role of angiogenesis target therapy has been approved in cancer treatment, the way to optimize the dose of angiogenesis inhibitors remains to be determined because of the lack of reliable surrogate markers of tumor angiogenesis. Shaked et al. reported that the levels of circulating endothelial progenitor cells (EPC), which contribute to the tumor vessel formation, reflect the anti-tumor efficacy of anti-angiogenesis regimens (9,10). Growing evidence suggests that the levels of circulating EPC reflect the response to chemotherapy both in animal model and clinical trial (11-13). Thus, circulating EPC can be used as a marker for optimizing and monitoring the anti-angiogenesis therapy including angiogenesis inhibitors and chemotherapy.

Circulating endothelial cells (CEC), especially apoptotic CEC, were observed to increase in breast cancer patients with a clinical benefit (defined as a clinical response or a stable disease) after metronomic therapy (14). Preclinical models indicated that the source of apoptotic CEC was most likely the tumor vasculature (14).

Whether circulating EPC or CEC can be served as markers of CCRT efficacy and toxicity in cervical cancer or not remains undetermined. Since CCRT is now a standard treatment of locally advanced and high-risk cervical cancer, the development of the surrogate marker for monitoring CCRT response and optimize treatment intensity, again, is very important.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Cervical cancer stage Ib - IVA

Criteria

Inclusion Criteria:

  • Receiving chemoradiation

Exclusion Criteria:

  • Stage IVB
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00753610

Contacts
Contact: Yu-Jen Chen, MD,PhD 886 2 28094661 ext 3060 chenmdphd@yahoo.com

Locations
Taiwan
Mackay Memorial Hospital Recruiting
Taipei, Taiwan, 10449
Contact: Chia-Yuan Liu, MD       henry76@ms1.mmnh.org.tw   
Principal Investigator: Yu-Jen Chen, MD,PhD         
Sponsors and Collaborators
Mackay Memorial Hospital
National Science Council, Taiwan
Investigators
Principal Investigator: Yu-Jen Chen, MD,PhD Mackay Memorial Hospital
  More Information

No publications provided

Responsible Party: Department of Radiation Oncology, Mackay Memorial Hospital
ClinicalTrials.gov Identifier: NCT00753610     History of Changes
Other Study ID Numbers: MMH-I-S-354
Study First Received: September 15, 2008
Last Updated: September 15, 2008
Health Authority: Taiwan: Department of Health

Keywords provided by Mackay Memorial Hospital:
EPC
CCRT
Cervical cancer

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female

ClinicalTrials.gov processed this record on October 19, 2014