A Trial of Tamoxifen and Letrozole in Recurrent and Persistent Squamous Cell Carcinoma of the Cervix
TGOG1005
An Open, Randomized, Multi-center, Phase 2 Trial of Tamoxifen and Letrozole in Recurrent and Persistent Squamous Cell Carcinoma of the Cervix: the Efficacy and New Biomarkers
1 other identifier
interventional
44
1 country
7
Brief Summary
The investigators design a phase 2, open labeled, randomized trial of Tamoxifen (20 mg/day) and Letrozole (2.5 mg) in treatment of squamous carcinoma of the cervix. Forty four patients with recurrent or persistent disease will be recruited, randomized, treated and followed three-monthly for 12 months. The primary end point is the treatment response rates. Secondary end points include survivals, ECOG performance status, quality of life and efficacy of biomarkers in predicting the responses. Candidate biomarkers including ER, PR, GPER and HPV genotype in paraffin cancer tissues as well as methylated genes in the blood will be studied in relation to the therapeutic outcomes.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started May 2015
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2015
CompletedFirst Submitted
Initial submission to the registry
May 12, 2015
CompletedFirst Posted
Study publicly available on registry
June 26, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2017
CompletedJune 26, 2015
June 1, 2015
1.7 years
May 12, 2015
June 23, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
The response rate
The guideline for the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) will be followed. Target tumor will be identified and followed by CT scan. Other efficacy parameters are tumor markers (SCC), and pelvic examination and physical examination findings.
one year
Secondary Outcomes (4)
Progression-free survival
one year
Quality of life
one year
ECOG Performance Status
one year
Overall survival
one year
Study Arms (2)
tamoxifen
EXPERIMENTALtamoxifen 20 mg given everyday for 12 months
letrozole
ACTIVE COMPARATORletrozole 2.5 mg given everyday for 12 months
Interventions
Eligibility Criteria
You may qualify if:
- With a histology proven primary squamous cell carcinoma of the cervix prior to the treatment failure
- Must sign and date informed consent.
- With age between 30 and 85
- With tissue blocks of the recurrent cancer lesion or primary cancer lesion available for the study.
- With a treatment-free interval of at least 4 weeks.
- With currently (within 1 month) measurable (by CT) tumor of at least 2 cm in one diameter (at least twice the scan slice thickness), AND elevated SCC level over 2 folds of the institutional upper limit of normal (ULN),
- With a ECOG performance status score of 0 to 2,
- With adequate hematologic function (ANC≧500/uL and platelets≧50,000/uL),
- With adequate renal function (serum creatinine≦2.0 mg/dL; if higher, then creatinine clearance≧40 mL/min was required),
- With adequate hepatic function (ALT/AST ≦3.0 folds of ULN
You may not qualify if:
- With histology type other than SCC
- Had liver, brain metastasis or malignant ascites
- Those having multiple metastasis (more than one metastasis lesion)
- Whose cancer had been treated for more than three therapeutic courses \[including 1 primary therapy (Operation+ CCRT is considered 1 primary therapy) and 2 secondary therapies\] courses.
- Who have received any investigational drugs within 30 days prior to enrollment
- Who were pregnant or lactating
- Who are taking selective serotonin receptor inhibitors (SSRI) (eg. Prozac, Celexa, Lexapro, Lubox, Paxi, Zoloft, etc.)
- With pulmonary embolism or other veneous embolism
- With uncontrolled medical conditions such as cardiac disease, cirrhosis of liver, active on chronic hepatitis, diabetes mellitus, autoimmune disease.
- With current or prior therapy (less than 3 months ) of selective estrogen receptor modulators (SERMs) (tamoxifen, raloxifen, fulvestrant, etc.), or aromatase inhibitors (eg. Letrozole, Anastrozole, Exemestane, Vorozole, Formestane, Fadrozole, etc.)
- Currently taking Warfarin or Rivaroxaben .
- With history of malignant disease, except those had been disease-free for at least 5 years.
- Patient who had allergy history to Tamoxifen or Letrozole
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Buddhist Tzu Chi General Hospitallead
- Chang Gung Memorial Hospitalcollaborator
- Chung Shan Medical Universitycollaborator
- China Medical University Hospitalcollaborator
- National Cheng-Kung University Hospitalcollaborator
- Kaohsiung Medical University Chung-Ho Memorial Hospitalcollaborator
- Kaohsiung Veterans General Hospital.collaborator
- Ministry of Science and Technology, Taiwancollaborator
Study Sites (7)
Dept. of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, No 123, Dapi Rd, Niaosong Dist, 83301, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, No.100, Ziyou 1st Rd., Sanmin Dist., 807-56, Taiwan
Chung Shan Medical University Hospital
Taichung, No.110,sec. 1,Jianguo NRd.,South Dist., 40201, Taiwan
National Cheng Kung University Hospital
Tainan, No.138, Shengli Rd., North Dist., 70403, Taiwan
China Medical University Hospital
Taichung, No.2, Yude Rd., North Dist.,, 40447, Taiwan
Kaohsiung Veterans General Hospital
Kaohsiung City, No.386, Dazhong 1st Rd., Zuoying Dist., 81362, Taiwan
Department of OB/GYN, Linkou Chang Geng Memorial Hospital
Taoyuan District, Taoyuan, 333, Taiwan
Related Publications (10)
Plummer M, Peto J, Franceschi S; International Collaboration of Epidemiological Studies of Cervical Cancer. Time since first sexual intercourse and the risk of cervical cancer. Int J Cancer. 2012 Jun 1;130(11):2638-44. doi: 10.1002/ijc.26250. Epub 2011 Aug 12.
PMID: 21702036BACKGROUNDRodriguez AC, Schiffman M, Herrero R, Hildesheim A, Bratti C, Sherman ME, Solomon D, Guillen D, Alfaro M, Morales J, Hutchinson M, Katki H, Cheung L, Wacholder S, Burk RD. Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection. J Natl Cancer Inst. 2010 Mar 3;102(5):315-24. doi: 10.1093/jnci/djq001. Epub 2010 Feb 15.
PMID: 20157096BACKGROUNDInternational Collaboration of Epidemiological Studies of Cervical Cancer. Cervical carcinoma and reproductive factors: collaborative reanalysis of individual data on 16,563 women with cervical carcinoma and 33,542 women without cervical carcinoma from 25 epidemiological studies. Int J Cancer. 2006 Sep 1;119(5):1108-24. doi: 10.1002/ijc.21953.
PMID: 16570271BACKGROUNDInternational Collaboration of Epidemiological Studies of Cervical Cancer; Appleby P, Beral V, Berrington de Gonzalez A, Colin D, Franceschi S, Goodhill A, Green J, Peto J, Plummer M, Sweetland S. Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies. Lancet. 2007 Nov 10;370(9599):1609-21. doi: 10.1016/S0140-6736(07)61684-5.
PMID: 17993361BACKGROUNDRiley RR, Duensing S, Brake T, Munger K, Lambert PF, Arbeit JM. Dissection of human papillomavirus E6 and E7 function in transgenic mouse models of cervical carcinogenesis. Cancer Res. 2003 Aug 15;63(16):4862-71.
PMID: 12941807BACKGROUNDShai A, Brake T, Somoza C, Lambert PF. The human papillomavirus E6 oncogene dysregulates the cell cycle and contributes to cervical carcinogenesis through two independent activities. Cancer Res. 2007 Feb 15;67(4):1626-35. doi: 10.1158/0008-5472.CAN-06-3344.
PMID: 17308103BACKGROUNDArbeit JM, Howley PM, Hanahan D. Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in human papillomavirus type 16 transgenic mice. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2930-5. doi: 10.1073/pnas.93.7.2930.
PMID: 8610145BACKGROUNDElson DA, Riley RR, Lacey A, Thordarson G, Talamantes FJ, Arbeit JM. Sensitivity of the cervical transformation zone to estrogen-induced squamous carcinogenesis. Cancer Res. 2000 Mar 1;60(5):1267-75.
PMID: 10728686BACKGROUNDBrake T, Connor JP, Petereit DG, Lambert PF. Comparative analysis of cervical cancer in women and in a human papillomavirus-transgenic mouse model: identification of minichromosome maintenance protein 7 as an informative biomarker for human cervical cancer. Cancer Res. 2003 Dec 1;63(23):8173-80.
PMID: 14678972BACKGROUNDBrake T, Lambert PF. Estrogen contributes to the onset, persistence, and malignant progression of cervical cancer in a human papillomavirus-transgenic mouse model. Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2490-5. doi: 10.1073/pnas.0409883102. Epub 2005 Feb 7.
PMID: 15699322BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Tang Yuan Chu, PhD
Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, 707, Section 3, Chung Yang Road, Hualien 970, Taiwan (R.O.C.)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- The Chief of Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital
Study Record Dates
First Submitted
May 12, 2015
First Posted
June 26, 2015
Study Start
May 1, 2015
Primary Completion
January 1, 2017
Study Completion
June 1, 2017
Last Updated
June 26, 2015
Record last verified: 2015-06