Urothelial CarcinomaNCT01993966
EGCG Modulate the Cytotoxic Effects of Chemotherapeutic Agents in Human Urothelial Carcinoma Cells
An observational study of Urothelial Carcinoma, run by National Taiwan University Hospital at 2 sites in Taiwan.
Trial summary
Urothelial carcinoma (UC) is the most common cancer of urinary tract. Patients with metastatic UC are usually treated with systemic chemotherapy. There still existed 30% to 50% of advanced UC not responsive to cisplatin-based chemotherapy; the prognosis for patients with metastatic UC remains poor. Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Urothelial Carcinoma
- How many people
- 25 participants
- Where
- 2 sitesTaiwan
- Study dates
- Jan 2014to Dec 2016
- How long will I take part?
- 1 Day
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: patients with age between 20-80 years old and had taken Radical Cystectomy or nephrectomy between 2008-2012 were chosen as study population
Who may be able to join
- In January 2008 to December 2012 at the National Taiwan University Hospital for surgery (radical resection of kidney and ureter or bladder removal) of urothelial carcinoma histopathology specimens of patients willing to participate in this study and the subjects described in the consent Book signer.
Who cannot join
- In January 2008 to December 2012 at the National Taiwan University Hospital for surgery (radical resection of kidney and ureter or bladder removal) of urothelial carcinoma histopathology specimens of patients are reluctant to join the researcher
Trial locations and contacts
2 sites in 1 country.
Chin-Ling Huang contact
Taiwan2 sites
Department of Urology, National Taiwan University Hospital
Taipei, No. 7, Chung Shans. Rd.,, 100
Kuo-How Huang, M.D.,Ph.D., 886-2-23123456
Chin-Ling Huang, 886-2-23123456 ext. 65233, d95447004@ntu.edu.tw
Department of Urology, National Taiwan University Hospital
Taipei, No. 7, Chung Shans. Rd., 100
Kuo-How Huang, M.D.,Ph.D., 886-2-23123456 ext. 65952, khhuang123@ntu.edu.tw
About this study
Official title: Mechanism of (-)-Epigallocatechin -3-gallate (EGCG) to Modulate the Cytotoxic Effects of Chemotherapeutic Agents in Human Urothelial Carcinoma Cells
Urothelial carcinoma (UC) is the most common cancer of urinary tract. Patients with metastatic UC are usually treated with systemic chemotherapy. There still existed 30% to 50% of advanced UC not responsive to cisplatin-based chemotherapy; the prognosis for patients with metastatic UC remains poor.
Read the detailed description
(-)-epigallocatechin -3-gallate (EGCG) is the most abundant polyphenol compound from green tea, representing ~16.5% of the water-extractable fraction. EGCG have various bioactivities and can bind and regulate a wide range of molecular involved in cell cycle, signal transduction, and protein degradation. However, the anticancer effects of EGCG on UC have not been thoroughly explored. Our preliminary data show that EGCG alone can inhibit cell proliferation and induce apoptosis with the activation of caspases and PARP in a time dependent manner. Moreover, EGCG can enhance the cytotoxicity of several chemotherapeutic drugs in vitro. The underlying mechanism seems to be associated with Akt and ERK pathway. We will also check the Akt and ERK protein level by immunohistochemical staining in clinically chemoreistant bladder urothelial carcinoma specimens to further prove our in vitro findings. We will further confirm the effect of chemotherapeutic drugs combined with EGCG on UC in vivo via xenograft model.
The specific aims of the study are:
- To explore the anti-tumor effects of EGCG on human UC cells and elucidate the possible mechanisms.
- To study the combinative cytotoxic effect of EGCG with other chemotherapeutic agents such as cisplatin, doxorubicin and gemcitabine on UC cells; moreover, to investigate the underlying mechanisms.
- To investigate the expression level of phospho-Akt and phospho-ERK in clinically chemoreistant bladder urothelial carcinoma specimens to further confirm our finding in clinical events. .
- To prove the in vitro findings and confirm the combinative efficacy of EGCG with chemotherapeutic agents in vivo by using the xenograft animal model.
- To establish a novel therapeutic strategy for treatment of UC.
- Conditions
- Urothelial Carcinoma
- Keywords
- Urothelial carcinoma (UC),, (-)-epigallocatechin-3-gallate(EGCG),, chemotherapy,, cytotoxicity,, drug resistance,, xenograft.
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| drug-resistant | specimens com from drug-resistant bladder urothelial carcinoma patients | |
| normal | specimens come from normal bladder urothelial carcinoma patients | |
| non-tumoral | specimens come from non-tumoral patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
The IHC staining score
the IHC staining scores are acquired by IHC staining and assessed by pathologist. The comparisons between each specimen are determined by IHC scores.
Measured: at the time of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2013 (estimated)
- Study startJan 2014
- Primary completionDec 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 25 participants (estimated)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kuo-How Huang, M.D.,Ph.D., Principal investigator, No. 7, Chung Shans. Rd., Taipei, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01993966
- Sponsor's protocol ID
- 201308047RIN
- Other IDs
- 103-002509
- Status last verified
- Nov 2013
- First submitted
- 24 Oct 2013
- Last updated
- 25 Nov 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Hussain SA, James ND. The systemic treatment of advanced and metastatic bladder cancer. Lancet Oncol. 2003 Aug;4(8):489-97. doi: 10.1016/s1470-2045(03)01168-9.
PubMed 12901963Ueki O, Hisazumi H, Uchibayashi T, Naito K, Tajiri S, Takemae K, Kawaguchi K, Kameda K, Nishino A, Nango C, et al. Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced urothelial cancer. Cancer Chemother Pharmacol. 1992;30 Suppl:S72-6. doi: 10.1007/BF00686947.
PubMed 1394823Tachibana H. Molecular basis for cancer chemoprevention by green tea polyphenol EGCG. Forum Nutr. 2009;61:156-169. doi: 10.1159/000212748. Epub 2009 Apr 7.
PubMed 19367120Yang CS, Wang X, Lu G, Picinich SC. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer. 2009 Jun;9(6):429-39. doi: 10.1038/nrc2641.
PubMed 19472429Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007 Jun 29;129(7):1261-74. doi: 10.1016/j.cell.2007.06.009.
PubMed 17604717
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanism of (-)-Epigallocatechin -3-gallate (EGCG) to Modulate the Cytotoxic Effects of Chemotherapeutic Agents in Human Urothelial Carcinoma Cells
- ClinicalTrials.gov ID
- NCT01993966
- Acronym / sponsor ID
- 201308047RIN
- Conditions
- Urothelial Carcinoma
- Keywords
- Urothelial carcinoma (UC),, (-)-epigallocatechin-3-gallate(EGCG),, chemotherapy,, cytotoxicity,, drug resistance,, xenograft.
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 25 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Urothelial carcinoma (UC) is the most common cancer of urinary tract. Patients with metastatic UC are usually treated with systemic chemotherapy. There still existed 30% to 50% of advanced UC not responsive to cisplatin-based chemotherapy; the prognosis for patients with metastatic UC remains poor.
Detailed description
(-)-epigallocatechin -3-gallate (EGCG) is the most abundant polyphenol compound from green tea, representing ~16.5% of the water-extractable fraction. EGCG have various bioactivities and can bind and regulate a wide range of molecular involved in cell cycle, signal transduction, and protein degradation. However, the anticancer effects of EGCG on UC have not been thoroughly explored. Our preliminary data show that EGCG alone can inhibit cell proliferation and induce apoptosis with the activation of caspases and PARP in a time dependent manner. Moreover, EGCG can enhance the cytotoxicity of several chemotherapeutic drugs in vitro. The underlying mechanism seems to be associated with Akt and ERK pathway. We will also check the Akt and ERK protein level by immunohistochemical staining in clinically chemoreistant bladder urothelial carcinoma specimens to further prove our in vitro findings. We will further confirm the effect of chemotherapeutic drugs combined with EGCG on UC in vivo via xenograft model.
The specific aims of the study are:
- To explore the anti-tumor effects of EGCG on human UC cells and elucidate the possible mechanisms.
- To study the combinative cytotoxic effect of EGCG with other chemotherapeutic agents such as cisplatin, doxorubicin and gemcitabine on UC cells; moreover, to investigate the underlying mechanisms.
- To investigate the expression level of phospho-Akt and phospho-ERK in clinically chemoreistant bladder urothelial carcinoma specimens to further confirm our finding in clinical events. .
- To prove the in vitro findings and confirm the combinative efficacy of EGCG with chemotherapeutic agents in vivo by using the xenograft animal model.
- To establish a novel therapeutic strategy for treatment of UC.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Target follow-up
- 1 Day
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| drug-resistant | – | –specimens com from drug-resistant bladder urothelial carcinoma patients |
| normal | – | –specimens come from normal bladder urothelial carcinoma patients |
| non-tumoral | – | –specimens come from non-tumoral patients |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients with age between 20-80 years old and had taken Radical Cystectomy or nephrectomy between 2008-2012 were chosen as study population
Key inclusion criteria (1 listed)
- In January 2008 to December 2012 at the National Taiwan University Hospital for surgery (radical resection of kidney and ureter or bladder removal) of urothelial carcinoma histopathology specimens of patients willing to participate in this study and the subjects described in the consent Book signer.
Key exclusion criteria (1 listed)
- In January 2008 to December 2012 at the National Taiwan University Hospital for surgery (radical resection of kidney and ureter or bladder removal) of urothelial carcinoma histopathology specimens of patients are reluctant to join the researcher
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The IHC staining score
Time frame: at the time of surgery
the IHC staining scores are acquired by IHC staining and assessed by pathologist. The comparisons between each specimen are determined by IHC scores.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2013.
- Background: PubMed 12901963Hussain SA, James ND. The systemic treatment of advanced and metastatic bladder cancer. Lancet Oncol. 2003 Aug;4(8):489-97. doi: 10.1016/s1470-2045(03)01168-9.
- Background: PubMed 1394823Ueki O, Hisazumi H, Uchibayashi T, Naito K, Tajiri S, Takemae K, Kawaguchi K, Kameda K, Nishino A, Nango C, et al. Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced urothelial cancer. Cancer Chemother Pharmacol. 1992;30 Suppl:S72-6. doi: 10.1007/BF00686947.
- Background: PubMed 19367120Tachibana H. Molecular basis for cancer chemoprevention by green tea polyphenol EGCG. Forum Nutr. 2009;61:156-169. doi: 10.1159/000212748. Epub 2009 Apr 7.
- Background: PubMed 19472429Yang CS, Wang X, Lu G, Picinich SC. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer. 2009 Jun;9(6):429-39. doi: 10.1038/nrc2641.
- Background: PubMed 17604717Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007 Jun 29;129(7):1261-74. doi: 10.1016/j.cell.2007.06.009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chin-Ling Huang contact
Kuo-How Huang, M.D.,Ph.D. principal investigator
No. 7, Chung Shans. Rd., Taipei, Taiwan
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Urothelial Carcinoma, run by National Taiwan University Hospital at 2 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kuo-How Huang, M.D., Ph.D. (886-2-23123456 ext. 65952, khhuang123@ntu.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The IHC staining score (time frame: at the time of surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01993966, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2013.