A Trial of Tamoxifen and Letrozole in Recurrent and Persistent Squamous Cell Carcinoma of the Cervix (TGOG1005)

June 23, 2015 updated by: Tang Yuan Chu, Buddhist Tzu Chi General Hospital

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Although human papillomavirus (HPV) is a necessary cause of cervical cancer, HPV infection itself is inefficient and insufficient to cause cancer. New evidences have suggested endogenous and exogenous sex hormones confer risk of developing cervical cancer. In unscreened populations, incidence of cervical cancer starts after menarche and constantly increases before menopause, after then the incidence is flattening and declines [21]. Indeed, after menopause, newly incident CIN3 is seldom detected[22]. Large-scale epidemiological studies also showed high number of full-term pregnancy[23] (rather than abortion) and long-term use of hormonal contraceptives[24] to be independent risk factors of cervical cancer. These evidences pointed to female sex hormones to be another culprit of cervical cancer.

The role of estrogen and ERα on HPV-induced cervical carcinogenesis is best demonstrated by the pK14-HPV E6/E7transgenic mice which, without estrogen exposure, develop benign skin tumors only. However, when these mice are treated with exogenous estradiol at physiological level, they develop cervical cancers in nearly 100% efficiency[25-28]. These cervical neoplasia recapitulate characteristics of human cervical cancer in all aspects: originated from the squamous-columnar junction, with early lesions of atypical squamous metaplasia, CIN and to invasive squamous cell carcinoma [29]. Most importantly, removal of exogenous estrogen or castration of these mice led to diminish of progression and partial regression of pre-existing neoplasia[30].

The investigators design an open, randomized, multi-center trial of tamoxifen and letrozole in treatment of recurrent or persistent squamous cell carcinoma of the cervix. Patients with recurrent or persistent SCC of cervix who are not amenable for further cytotoxic treatment will be randomized by block and by participating center to one of the two arms. The block size will be two . Medication will be given orally in daily dose of tamoxifen (Nolvadex) 20 mg, letrozole (Femara) 2.5 mg until disease progression or until the end of the study.

Primary end point of the study is the response rate (complete response and partial response rates) for tamoxifen and letrozole arms. Secondary end points include progression-free survival (PFS) and overall survival (OS) compared to the historical results, ECOG Performance Status, quality of life and outcome predictors (biomarkers and clinical characteristics) of responsiveness and survival. The experienced survival data of the participating center will be compared.

Study Type

Interventional

Enrollment (Anticipated)

44

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taoyuan, Taiwan, 333
        • Recruiting
        • Department of OB/GYN, Linkou Chang Geng Memorial Hospital
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Ting-Chang Chang, MD
        • Sub-Investigator:
          • Kuan-Gen Huang, MD
        • Sub-Investigator:
          • Angel Chao, PhD
        • Sub-Investigator:
          • Cheng-Tao Lin, MD
        • Sub-Investigator:
          • Jian-Tai Qiu, MD
        • Sub-Investigator:
          • Min-Yu Chen, MD
        • Sub-Investigator:
          • Yunhsin Tang, MD
        • Sub-Investigator:
          • Hung-Hsueh Chou, MD
    • No 123, Dapi Rd, Niaosong Dist
      • Kaohsiung, No 123, Dapi Rd, Niaosong Dist, Taiwan, 83301
        • Not yet recruiting
        • Dept. of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Hao Lin, Bachelor
        • Sub-Investigator:
          • Yu-Che Ou, Bachelor
        • Sub-Investigator:
          • Ching-Chou Tsai, Master
        • Sub-Investigator:
          • Chen-Hsuan Wu, Bachelor
    • No.100, Ziyou 1st Rd., Sanmin Dist.
      • Kaohsiung, No.100, Ziyou 1st Rd., Sanmin Dist., Taiwan, 807-56
        • Not yet recruiting
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
        • Contact:
        • Contact:
    • No.110,sec. 1,Jianguo NRd.,South Dist.
      • Taichung, No.110,sec. 1,Jianguo NRd.,South Dist., Taiwan, 40201
        • Not yet recruiting
        • Chung Shan Medical University Hospital
        • Contact:
    • No.138, Shengli Rd., North Dist.
      • Tainan, No.138, Shengli Rd., North Dist., Taiwan, 70403
        • Not yet recruiting
        • National Cheng Kung University Hospital
        • Contact:
          • Ching-I Wu, Bachelor
        • Contact:
    • No.2, Yude Rd., North Dist.,
      • Taichung, No.2, Yude Rd., North Dist.,, Taiwan, 40447
        • Not yet recruiting
        • China Medical University Hospital
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Yao-Ching Hung, PhD
    • No.386, Dazhong 1st Rd., Zuoying Dist.
      • Kaohsiung, No.386, Dazhong 1st Rd., Zuoying Dist., Taiwan, 81362
        • Not yet recruiting
        • Kaohsiung Veterans General Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

28 years to 83 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. With a histology proven primary squamous cell carcinoma of the cervix prior to the treatment failure
  2. Must sign and date informed consent.
  3. With age between 30 and 85
  4. With tissue blocks of the recurrent cancer lesion or primary cancer lesion available for the study.
  5. With a treatment-free interval of at least 4 weeks.
  6. 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),
  7. With a ECOG performance status score of 0 to 2,
  8. With adequate hematologic function (ANC≧500/uL and platelets≧50,000/uL),
  9. With adequate renal function (serum creatinine≦2.0 mg/dL; if higher, then creatinine clearance≧40 mL/min was required),
  10. With adequate hepatic function (ALT/AST ≦3.0 folds of ULN

Exclusion Criteria:

  1. With histology type other than SCC
  2. Had liver, brain metastasis or malignant ascites
  3. Those having multiple metastasis (more than one metastasis lesion)
  4. 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.
  5. Who have received any investigational drugs within 30 days prior to enrollment
  6. Who were pregnant or lactating
  7. Who are taking selective serotonin receptor inhibitors (SSRI) (eg. Prozac, Celexa, Lexapro, Lubox, Paxi, Zoloft, etc.)
  8. With pulmonary embolism or other veneous embolism
  9. With uncontrolled medical conditions such as cardiac disease, cirrhosis of liver, active on chronic hepatitis, diabetes mellitus, autoimmune disease.
  10. 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.)
  11. Currently taking Warfarin or Rivaroxaben .
  12. With history of malignant disease, except those had been disease-free for at least 5 years.
  13. Patient who had allergy history to Tamoxifen or Letrozole

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: tamoxifen
tamoxifen 20 mg given everyday for 12 months
Drug: tamoxifen
tamoxifen was given 20 mg qd for 12 months or till disease progress
Other Names:
  • Nolvadex
Active Comparator: letrozole
letrozole 2.5 mg given everyday for 12 months
Drug: Letrozole
letrozole 2.5 mg qd was given for 12 months or till disease progress
Other Names:
  • Femara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The response rate
Time Frame: one year
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: one year
Progression-free survival (PFS) comparing to the historical results
one year
Quality of life
Time Frame: one year
The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life questionnaire cervical cancer module: EORTC QLQ-CX24 and C30 will be evaluated for every patient at every visit during study period.
one year
ECOG Performance Status
Time Frame: one year
ECOG Performance status will be evaluated every visit during study period
one year
Overall survival
Time Frame: one year
overall survival (OS) comparing to the historical results
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Buddhist Tzu Chi General Hospital

Collaborators

China Medical University Hospital
Chang Gung Memorial Hospital
Kaohsiung Medical University Chung-Ho Memorial Hospital
National Cheng-Kung University Hospital
Kaohsiung Veterans General Hospital.
Chung Shan Medical University
Taiwan Ministry of Science and Technology

Investigators

  • 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.)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2015

Primary Completion (Anticipated)

January 1, 2017

Study Completion (Anticipated)

June 1, 2017

Study Registration Dates

First Submitted

May 12, 2015

First Submitted That Met QC Criteria

June 23, 2015

First Posted (Estimate)

June 26, 2015

Study Record Updates

Last Update Posted (Estimate)

June 26, 2015

Last Update Submitted That Met QC Criteria

June 23, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TGOG1005

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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