Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Uterine Cervical Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Letrozole

Estrogen Receptor Modulators

Estrogen Antagonists

Estrogen Receptor Antagonists

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

tamoxifen 20 mg given everyday for 12 months

letrozole 2.5 mg given everyday for 12 months

letrozole 2.5 mg qd was given for 12 months or till disease progress

tamoxifen was given 20 mg qd for 12 months or till disease progress

tamoxifen

Mun Kun Hong, MD

Tang Yuan Chu, PhD

Chan-Chao Chang, Bachelor

Hung-Chung Fu

Hao Lin, Bachelor

Yu-Che Ou, Bachelor

Ching-Chou Tsai, Master

Chen-Hsuan Wu, Bachelor

Yu-Chieh Chen, Master

Chih-Jen Tseng, Master

Ching-I Wu, Bachelor

Ya-Min Cheng

Wu-Chou Lin, PhD

Lian-Shung Yeh, Master

Yao-Ching Hung, PhD

Wen-Shiung Liou, MD

Chyong-Huey Lai, .MD

Huei-Jean Huang, MD

Ting-Chang Chang, MD

Kuan-Gen Huang, MD

Angel Chao, PhD

Cheng-Tao Lin, MD

Jian-Tai Qiu, MD

Min-Yu Chen, MD

Yunhsin Tang, MD

Hung-Hsueh Chou, MD

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.

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.

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

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 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.

Progression-free survival (PFS) comparing to the historical results

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.

ECOG Performance status will be evaluated every visit during study period

overall survival (OS) comparing to the historical results

Chang Gung Memorial Hospital

Chung Shan Medical University

China Medical University Hospital

National Cheng-Kung University Hospital

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung Veterans General Hospital.

Taiwan Ministry of Science and Technology

Buddhist Tzu Chi General Hospital

The Chief of Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital

Skin and Connective Tissue Diseases

Breast Neoplasms

Carcinogenesis

Breast Diseases

Skin Diseases

Lipid Regulating Agents

Other Dietary Supplements

Pitavastatin

Raloxifene Hydrochloride

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Omega 3 Fatty Acid

Lovaza 4 gm/day oral capsule with meals plus Raloxifene 30 mg oral tablet daily

Dietary supplement; Take 4 mg oral capsules daily

Lovaza 4gm oral

Raloxifene 60 Mg Oral Tablet

Raloxifene 30 Mg Oral Tablet

Lovaza 4gm and Raloxifene 30 Mg orally once per day for 2 years

Lovaza 4gm & Raloxifene 30mg

Andrea Manni, MD

The overall hypothesis is that the combination of a low dose of the antiestrogen Raloxifene with omega-3 fatty acids will exert a synergistic breast cancer chemopreventive effect due to the crosstalk of their downstream cellular effects leading to decreased proliferation and increased apoptosis of premalignant mammary cells. Based on the investigators hypothesis that upregulation of functional estrogen receptors in the premalignant lesions is also responsible for the development of hormone independent tumors, the investigators postulate that the combination of antiestrogens and omega-3 fatty acids will reduce the development of both hormone-dependent and -independent tumors. At present, there are no known interventions able to decrease the development of hormone-independent tumors, which are more prevalent, more aggressive, leading to the patient's demise. In addition, the investigators postulate that this approach will be safe since it will combine a lower and hence a less toxic dose of Raloxifene with the administration of omega-3 fatty acids which are known to have health benefits, i.e., reduction in cardiovascular risk, beyond their possible chemo preventive effect in breast cancer.

The main objectives of this study are to determine the individual and combined effects of Raloxifene and omega-3 fatty acids on surrogate markers of breast cancer development in healthy, postmenopausal women. The primary endpoint will be mammographic density for which the study has been powered. Breast density is a major risk factor for breast cancer and hence it is chosen to evaluate the potential chemopreventive efficacy of our interventions. Secondary endpoints would include markers of oxidative stress, parameters of estrogen metabolism, markers of inflammation, and markers of IGF-I signaling, all of which have been shown in the literature to have an influence on mammary carcinogenesis.

Study Population: Healthy, postmenopausal women between the ages of 35-70 years, undergoing yearly mammograms as part of routine screening practice.

Method of Identification of Subjects/Samples/Medical Records: Women reporting for yearly mammograms will be considered for this protocol. They will be given first a screening questionnaire to rule out any co-existing medical condition that would predispose them to thromboembolic events.

Nutritional Supplements and Hormonal Manipulations for Breast Cancer Prevention

Combination of Low Dose Antiestrogens With Omega-3 Fatty Acids for Prevention of Hormone-independent Breast Cancer

Change of absolute breast density as indicated by mammography from baseline to Year +1 and completion of study (Year +2). No other mammograms will be obtained or used for the purpose of this study. Absolute breast density volume is based on breast thickness and the x-ray attenuation at each pixel of the image.

Changes in biomarkers for oxidative stress. Specific time points for evaluation are baseline and Year +1 (only). Urinary 8-(isoprostane) F-2α as measured through urine analysis.

Changes in biomarkers for oxidative stress. Specific time points for evaluation are baseline and Year +1 (only). Urinary 8-hydroxy-deoxyguansine as measured through urinary analysis.

Changes in biomarkers for estrogen metabolism: 2-hydroxy estrone (Urinary 2-OHE1) and 16-α-hydroxy estrone (16α-OHE1) as measured by urinary analysis. Specific time points for evaluation are baseline and Year +1 (only).

Changes in serum biomarkers for inflammation including highly sensitive C-reactive protein and IL-6 obtained through a blood draw. Specific time points for evaluation are baseline and Year +1 (only).

Changes in insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-1 binding protein-3 (IGFBP-3) obtained through blood sample. Specific time points for evaluation are baseline and Year +1 (only).

Changes in serum lipid levels as measured through total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. Specific time points for evaluation are baseline, Year +1, and Year 2.

Changes in complete blood count levels as measured through red blood cells (RBC). Specific time points for evaluation are baseline, Year +1, and Year 2.

Changes in complete blood count levels as measured through hemoglobin. Specific time points for evaluation are baseline, Year +1, and Year 2.

Changes in complete blood count levels as measured through hematocrit percentage. Specific time points for evaluation are baseline, Year +1, and Year 2.

Changes in complete blood count levels as measured through white blood cells (WBC) and platelets. Specific time points for evaluation are baseline, Year +1, and Year 2.

Milton S. Hershey Medical Center

Professor and Chief Division of Endocrinology, Diabetes, and Metabolism

Group 1: Control

Group 2: Raloxifene 60 mg

Group 3: Raloxifene 30 mg

Group 4: Lovaza 4 gm

Lovaza 4 gm/day orally with meals plus Raloxifene 30 mg orally daily

Group 5: Lovaza 4 gm and Raloxifene 30 mg

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. Andrea Manni

Absolute density at baseline

Absolute density at 1 year

Absolute density at 2 years

The decrease in the population groups is accounted for through subject withdrawals, subjects lost to follow-up, and other reasons for not completing study.

Change in Absolute Breast Density

Baseline

1 year

Biomarker measurements were not taken for the entire population of the study due to non-significant trends for treatment effects found in this population (n = 47).

Changes in Biomarkers for Oxidative Stress:Urinary 8-(Isoprostane) F-2α

Changes in Biomarkers for Oxidative Stress: Urinary 8-hydroxy-deoxyguansine

Baseline: Urinary 2-OHE1

1 year: Urinary 2-OHE1

Baseline: 16α-OHE1

1 year: 16α-OHE1

Changes in Biomarkers for Estrogen Metabolism: 2-hydroxy Estrone (Urinary 2-OHE1) and 16-α-hydroxy Estrone (16α-OHE1)

Baseline: Serum hsCRP

1 year: Serum hsCRP

Baseline: Serum IL-6

1 year: Serum IL-6

Biomarker measurements were not taken for the entire population of the study (N = 266) due to non-significant trends for treatment effects found in this initial population (n = 89).

Changes in Serum Biomarkers for Inflammation From Levels of High Sensitivity C-reactive Protein (hsCRP) and Interleukin 6 (IL-6)

Baseline: IGF-1

1 year: IGF-1

Baseline: IGFBP-3

1 year: IGFBP-3

Measurements were not taken for the entire population of the study due to non-significant trends for treatment effects found in this population (n = 46).

Changes in Insulin-like Growth Factor-1 (IGF-1) and Insulin-like Growth Factor-1 Binding Protein-3 (IGFBP-3)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Trial of Tamoxifen and Letrozole in Recurrent and Persistent Squamous Cell Carcinoma of the Cervix	NCT02482740	Uterine Cervica...	Letrozole tamoxifen	30 Years - 85 Years	Buddhist Tzu Chi General Hospital
A Trial of Tamoxifen and Letrozole in Recurrent and Persistent Squamous Cell Carcinoma of the Cervix	NCT02482740	Uterine Cervica...	Letrozole tamoxifen	30 Years - 85 Years	Buddhist Tzu Chi General Hospital
Nutritional Supplements and Hormonal Manipulations for Breast Cancer Prevention	NCT00723398	Breast Cancer	Lovaza 4gm oral Raloxifene 60 M... Raloxifene 30 M... Lovaza 4gm & Ra...	35 Years - 70 Years	Milton S. Hershey Medical Center
A Trial of Tamoxifen and Letrozole in Recurrent and Persistent Squamous Cell Carcinoma of the Cervix	NCT02482740	Uterine Cervica...	Letrozole tamoxifen	30 Years - 85 Years	Buddhist Tzu Chi General Hospital

Spots Global Cancer Trial Database for antiestrogens