Advanced Colorectal AdenomasPhase 2NCT01606124
Polyphenon E in Treating Patients With High-Risk of Colorectal Cancer
A Phase 2 study testing defined green tea catechin extract, questionnaire administration and laboratory biomarker analysis in people with Advanced Colorectal Adenomas and Adenocarcinoma of the Colon, run by Mayo Clinic at 3 sites in United States.
Trial summary
This phase II trial studies how well Polyphenon E works in treating patients with high-risk of colorectal cancer. Polyphenon E contains ingredients that may prevent or slow colorectal cancer. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Advanced Colorectal Adenomas, Adenocarcinoma of the Colon, Stage I Colon Cancer
- What is being tested?
- defined green tea catechin extract, questionnaire administration and laboratory biomarker analysis
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 3 sitesUnited States
- Study dates
- Jun 2012to 21 May 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Current or prior advanced adenomas. Participants with advanced adenomas are defined as participants who have polyps >= 1 cm, who have tubulovillous adenomas (25-75 percent villous features), who have villous adenomas (>75 percent villous), or who have severe dysplasia
- Prior curatively resected Tumor, Node, Metastasis (TNM) stage II and III colon cancer >= 3 years out from treatment by surgery with/without adjuvant chemotherapy; NOTE: patients with stage I (T1,2 N0) colon cancer treated by endoscopic or surgical therapy are eligible at anytime after such therapy; patients with prior stage IV disease must be >= 5 years status post surgical resection of all metastatic disease
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Ability to understand and the willingness to sign a written informed consent document
- Willingness to discontinue regular usage of calcium supplements; Exception: multi-vitamin; regular use defined as a frequency of 7 consecutive days for > 3 weeks
- Willingness to provide mandatory tissue and blood for protocol specified research; residual tissue and/or blood may be used for future research Negative pregnancy test =< 7 days prior to registration/randomization
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- Hemoglobin (Hgb) >= 12.0 g/dL (women), >= 13.5 g/dL (men) at Mayo Clinic or within normal limits at an outside laboratory
- Platelet count >= 100,000/ul
- White blood cells (WBC) >= 3,000/ul
- Alanine aminotransferase (ALT) within institutional limits of normal
- Alkaline phosphatase within institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) within institutional limits of normal
- Total bilirubin within institutional limits of normal
- Serum calcium =< institutional ULN
- Serum creatinine =< 1.5 x institutional ULN
- >= 5 rectal ACF detected by chromoendoscopy =< 45 days prior to registration/randomization
- Endoscopy =< 45 days prior to registration/randomization; Note: All adenomas or polyps will be removed according to institutional standards of care, and the cecum must visualized; this may be done at the same time as the chromoendoscopy
Who cannot join
- Any history of rectal cancer; Exception: transanal excision without radiation
- Known diagnosis of colon heritable cancer syndrome (Familial adenomatous polyposis [FAP], hereditary nonpolyposis colorectal cancer [HNPCC]) or inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- Inability to swallow capsules
- Bleeding diathesis
- Any invasive malignancy =< 5 years prior to pre-registration;
- Exceptions:
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- patients with nonmelanoma skin cancers that were treated with simple excisional biopsy or stage I (T1,2 N0)
- colon cancer treated by endoscopic therapy or surgery are eligible
- History of gastroduodenal ulcers documented =< 1 year
- Known inability to participate in the scheduled follow-up tests
- Significant medical or psychiatric problems which would make the participant a poor protocol candidate, in the opinion of the treating physician
- Total colectomy
- Colostomy
- History of pelvic or rectal radiation therapy
- History of liver disease
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
- Concomitant corticosteroids or anticoagulants needed on a regular or predictable intermittent basis
- Use of non-study investigational agent(s) =< 3 months prior to preregistration
- Chemotherapy =< 6 months prior to pre-registration; Note: Topical chemotherapy will be assessed on a case-by-case basis
- Any of the following: * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception Note: This study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown
- Over-the-counter green tea or green tea extract use =< 6 weeks prior to pre-registration; consumption of over the counter green tea extracts or drinking of green tea is not permitted during the treatment portion of this trial
- Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) =< 6 weeks prior to pre-registration; regular use of NSAIDs is defined as a frequency of 7 consecutive days (1 week) for > 3 weeks; participant must abstain from regular use of NSAIDs for the duration of the study; Exception: low dose aspirin (81 mg) for those participants who are chronic users of aspirin prior to the beginning of the study
- Use of non-study investigational agents while on study
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Illinois
Chicago, Illinois, 60612
Hines Veteran's Administration Hospital
Hines, Illinois, 60612
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: Randomized Phase II Trial of Polyphenon E vs.Placebo in Patients at High Risk of Recurrent Colonic Neoplasia
This phase II trial studies how well Polyphenon E works in treating patients with high-risk of colorectal cancer. Polyphenon E contains ingredients that may prevent or slow colorectal cancer.
Read the detailed description
PRIMARY OBJECTIVES: I. To determine whether POLYE (Polyphenon E) treatment is associated with a significant percent decrease in the number of rectal Aberrant Crypt Foci (ACF) (% change in ACF) identified during the pre-intervention and post-intervention chromoendoscopy exams. SECONDARY OBJECTIVES: I. To determine the relative tolerability and safety of treatment with 2 capsules of POLYE taken twice a day by mouth (Note: each capsule of Polyphenon E contains approximately 200 mg of epigallocatechin gallate (EGCG) versus placebo administered for 6 months. TERTIARY OBJECTIVES: I. To determine the effect of the study drug vs. placebo on EGCG levels in plasma and to correlate EGCG levels with drug compliance and toxicity. II. To characterize ACF based on four criteria and correlate such characterizations with the intervention (vs placebo), as well as exploring the natural history of ACF over 6 months in persons at high risk for colorectal cancer randomized to placebo. III. To correlate the 6-month measurements of ACF size (e.g., number of crypts/ACF), number, morphology, and histopathology with the adenoma recurrence data at the next surveillance endoscopy. IV. To assess caffeine and black tea consumption via a Beverage Consumption Questionnaire and correlate with study endpoints. V. To assess the effects of POLYE versus placebo on a focused panel of tissue biomarkers using re- and post-intervention biopsy samples obtained from ACF and normal-appearing rectal mucosa. Residual tissue will be stored for further analysis. VI. To study the association of clinical (toxicity and/or ACF response or activity) with the pharmacokinetic parameters, and/or biologic (pharmacodynamic) results. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive Polyphenon E orally (PO) twice daily (BID). ARM II: Patients receive placebo PO BID. Courses in both arms repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 5 years.
- Conditions
- Advanced Colorectal Adenomas, Adenocarcinoma of the Colon, Stage I Colon Cancer, Stage II Colon Cancer, Stage III Colon Cancer
- Being tested
- defined green tea catechin extract, placebo, questionnaire administration, laboratory biomarker analysis
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
defined green tea catechin extractDrug
Also called Polyphenon E
Given PO
placeboOther
Also called PLCB
Given PO
questionnaire administrationOther
Ancillary studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (Green Tea Catechin Extract) | Experimental | Patients receive Polyphenon E PO BID. Courses repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity. Receives: Drug: defined green tea catechin extract; Other: questionnaire administration; Other: laboratory biomarker analysis |
| Arm II (placebo) | Placebo comparator | Patients receive placebo PO BID. Courses repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity. Receives: Other: placebo; Other: questionnaire administration; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Rectal ACF, Pre- and Post Intervention at 6 Months
The primary endpoint is based on a modified intent-to-treat procedure which includes all patients with baseline and 6-month ACF data. The percent change in rectal ACF (≤ 15 cm from the anal verge) for each patient is calculated as their Pre-Registration number of rectal ACF minus the number of rectal ACF present at the 6-month post-intervention exam, divided by the number of rectal ACF present at Pre-Registration times 100.
Measured: 6 months
Secondary outcomes (1)
Tolerability as Estimated Using the Percent Dose of Treatment Received at 6 Months
Tolerability as estimated using the percent dose of treatment received for each patient by dividing the total dose received by the targeted (i.e., protocol specified) total dose.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2012 (estimated)
- Study startJun 2012
- Primary completion21 May 2015
- Study completion21 May 2015
Why it stopped: pending expiration of the supply of study agent.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Colorectal AdenomasStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Frank Sinicrope, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01606124
- Sponsor's protocol ID
- MC084C
- Other IDs
- NCI-2012-00058
- Status last verified
- May 2017
- First submitted
- 23 May 2012
- Last updated
- 27 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Trial of Polyphenon E vs.Placebo in Patients at High Risk of Recurrent Colonic Neoplasia
- ClinicalTrials.gov ID
- NCT01606124
- Acronym / sponsor ID
- MC084C
- Conditions
- Advanced Colorectal Adenomas, Adenocarcinoma of the Colon, Stage I Colon Cancer, Stage II Colon Cancer, Stage III Colon Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: pending expiration of the supply of study agent.
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2012
- Primary completion
- 21 May 2015 (actual)
- Study completion
- 21 May 2015 (actual)
- First posted
- 25 May 2012 (estimated)
- Results
- Posted 28 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well Polyphenon E works in treating patients with high-risk of colorectal cancer. Polyphenon E contains ingredients that may prevent or slow colorectal cancer.
Detailed description
PRIMARY OBJECTIVES: I. To determine whether POLYE (Polyphenon E) treatment is associated with a significant percent decrease in the number of rectal Aberrant Crypt Foci (ACF) (% change in ACF) identified during the pre-intervention and post-intervention chromoendoscopy exams. SECONDARY OBJECTIVES: I. To determine the relative tolerability and safety of treatment with 2 capsules of POLYE taken twice a day by mouth (Note: each capsule of Polyphenon E contains approximately 200 mg of epigallocatechin gallate (EGCG) versus placebo administered for 6 months. TERTIARY OBJECTIVES: I. To determine the effect of the study drug vs. placebo on EGCG levels in plasma and to correlate EGCG levels with drug compliance and toxicity. II. To characterize ACF based on four criteria and correlate such characterizations with the intervention (vs placebo), as well as exploring the natural history of ACF over 6 months in persons at high risk for colorectal cancer randomized to placebo. III. To correlate the 6-month measurements of ACF size (e.g., number of crypts/ACF), number, morphology, and histopathology with the adenoma recurrence data at the next surveillance endoscopy. IV. To assess caffeine and black tea consumption via a Beverage Consumption Questionnaire and correlate with study endpoints. V. To assess the effects of POLYE versus placebo on a focused panel of tissue biomarkers using re- and post-intervention biopsy samples obtained from ACF and normal-appearing rectal mucosa. Residual tissue will be stored for further analysis. VI. To study the association of clinical (toxicity and/or ACF response or activity) with the pharmacokinetic parameters, and/or biologic (pharmacodynamic) results. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive Polyphenon E orally (PO) twice daily (BID). ARM II: Patients receive placebo PO BID. Courses in both arms repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (Green Tea Catechin Extract) | Experimental | Drug: defined green tea catechin extract, Other: questionnaire administration, Other: laboratory biomarker analysisPatients receive Polyphenon E PO BID. Courses repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity. |
| Arm II (placebo) | Placebo comparator | Other: placebo, Other: questionnaire administration, Other: laboratory biomarker analysisPatients receive placebo PO BID. Courses repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Current or prior advanced adenomas. Participants with advanced adenomas are defined as participants who have polyps >= 1 cm, who have tubulovillous adenomas (25-75 percent villous features), who have villous adenomas (>75 percent villous), or who have severe dysplasia
- Prior curatively resected Tumor, Node, Metastasis (TNM) stage II and III colon cancer >= 3 years out from treatment by surgery with/without adjuvant chemotherapy; NOTE: patients with stage I (T1,2 N0) colon cancer treated by endoscopic or surgical therapy are eligible at anytime after such therapy; patients with prior stage IV disease must be >= 5 years status post surgical resection of all metastatic disease
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Ability to understand and the willingness to sign a written informed consent document
- Willingness to discontinue regular usage of calcium supplements; Exception: multi-vitamin; regular use defined as a frequency of 7 consecutive days for > 3 weeks
Key exclusion criteria (23 listed)
- Any history of rectal cancer; Exception: transanal excision without radiation
- Known diagnosis of colon heritable cancer syndrome (Familial adenomatous polyposis [FAP], hereditary nonpolyposis colorectal cancer [HNPCC]) or inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- Inability to swallow capsules
- Bleeding diathesis
- Any invasive malignancy =< 5 years prior to pre-registration;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| defined green tea catechin extractAlso: Polyphenon EGiven PO | Drug | Arm I (Green Tea Catechin Extract) |
| placeboAlso: PLCBGiven PO | Other | Arm II (placebo) |
| questionnaire administrationAncillary studies | Other | Arm I (Green Tea Catechin Extract), Arm II (placebo) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (Green Tea Catechin Extract), Arm II (placebo) |
Primary outcome
Percent Change in Rectal ACF, Pre- and Post Intervention at 6 Months
Time frame: 6 months
The primary endpoint is based on a modified intent-to-treat procedure which includes all patients with baseline and 6-month ACF data. The percent change in rectal ACF (≤ 15 cm from the anal verge) for each patient is calculated as their Pre-Registration number of rectal ACF minus the number of rectal ACF present at the 6-month post-intervention exam, divided by the number of rectal ACF present at Pre-Registration times 100.
1 secondary outcome
Tolerability as Estimated Using the Percent Dose of Treatment Received at 6 Months
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Frank Sinicrope principal investigator
Mayo Clinic
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing defined green tea catechin extract, questionnaire administration and laboratory biomarker analysis in people with Advanced Colorectal Adenomas and Adenocarcinoma of the Colon, run by Mayo Clinic at 3 sites in United States.
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 17 inclusion and 23 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: stopped early, as of the sponsor's last update on 27 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Rectal ACF, Pre- and Post Intervention at 6 Months (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Oct 2017.