Colorectal CancerPhase 2NCT01856322
Surgery Plus Sulindac or Surgery Alone for Advanced Colorectal Cancer
A Phase 2 study testing Sulindac and Validate assays and shipping methods in people with Colorectal Cancer and Liver Metastasis, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Some types of inflammation may increase the risk of cancers in the intestinal track. Because of this possibility, anti-inflammatory drugs may be able to prevent tumor growth and spread. One such drug, sulindac, may be helpful to study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Liver Metastasis, Colorectal Adenocarcinoma
- What is being tested?
- Sulindac and Validate assays and shipping methods
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2013to Jan 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age greater than 18
- Able to read and understand the informed consent
- No self-reported co morbidities of history of cancer
Who cannot join
- Women of child-bearing potential who are pregnant or breast feeding because of the potentially dangerous effects of the chemotherapy on the fetus or infant.
- Active systemic infections, coagulation disorders or other major medical illnesses precluding major surgery.
- Patients receiving warfarin anticoagulation, who cannot be transferred to other agents, such as low molecular weight heparins, anti-factor Xa (anti-Xa) agents, etc.
- Active bleeding disorders
- Patients with uncontrolled hypertension (would suggest: systolic blood pressure (SBP)> 155, diastolic blood pressure (DBP)> 90), unstable coronary disease (unstable angina, evidence of congestive heart failure (CHF), or myocardial infarction (MI) within 6-12 months of study)
- Childs B or C cirrhosis or with evidence of severe portal hypertension by history, endoscopy, or radiologic studies or with evidence of moderate to severe ascites.
Show all 9Show fewer
- Prior history of gastrointestinal (GI) bleeding unrelated to a cancer diagnosis
- Note: Patients who have a normal upper and lower endoscopy may be enrolled at the discretion of the principal investigator (PI).
- Renal insufficiency Discretion of principle investigator.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Phase 2 Prospective Randomized Double Blind Trial Comparing Metastasectomy Plus Sulindac Versus Metastasectomy Alone in Patients With Stage IV Colorectal Cancer
Background:
- Some types of inflammation may increase the risk of cancers in the intestinal track. Because of this possibility, anti-inflammatory drugs may be able to prevent tumor growth and spread. One such drug, sulindac, may be helpful to study. Researchers want to see if people who are having surgery to remove intestinal tumors from advanced colorectal cancer will benefit from sulindac. It will be tested against a placebo.
Read more
Objectives:
- To see if sulindac can improve treatment outcomes in people who are having surgery for advanced colorectal cancer.
Eligibility:
- Individuals at least 18 years of age who are having surgery for advanced colorectal cancer.
Design:
- Participants will be screened with a physical exam and medical history. Blood samples will be collected. Imaging studies and heart and lung function tests may also be given.
- Participants will be separated into two groups. One group will take sulindac. The other will take a placebo.
- Participants will take sulindac or placebo twice daily from about 2 to 3 weeks before the scheduled surgery. Seven days before the surgery, they will stop taking the pills.
- Participants will have surgery to remove their tumors. The surgery will also remove affected organ tissue.
- Participants will start to take the pills again once they have recovered from surgery. They will continue taking the sulindac or placebo twice a day for 3 years, or for as long as the tumors do not return.
Read the detailed description
- Despite strong evidence for a causative role of inflammatory mediators in intestinal cancer, the underlying mechanisms remain obscure. Established evidence indicates activation of the Wnt/beta-catenin pathway is an early step in the malignant transformation of colorectal adenomas with persistent activation in 90% of colorectal cancers. Activation of this pathway ultimately effects transcription of the S100A4 gene.
- S100A4 transcript serum levels have been shown to correlate with risk of recurrence in colorectal cancer and patients with systemic metastases are found to have increased S100A4 transcript expression.
- S100A4 may be a novel prognostic biomarker in colorectal cancer.
- Cyclooxygenase-2 is a key enzyme involved in the inflammatory response and is a key target of molecular chemoprevention in colorectal adenoma prevention trials.
- Recent studies demonstrate mitigation of Wnt/beta-catenin signaling by COX-2 inhibition via administration of the non-steroidal anti-inflammatory drug (NSAID) sulindac using in vitro and in vivo animal models.
- We hypothesize that sulindac administration will abrogate Wnt/beta-catenin mediated signaling and thus decrease S100A4 activity in patients with colorectal metastases.
- We propose to define the benefit of sulindac administration to patients with colorectal metastases following resection and validate the use of circulating S100A4 transcripts as a novel biomarker for disease recurrence.
- Being tested
- Sulindac, Placebo, Validate assays and shipping methods
- Keywords
- Colorectal Cancer, Liver Metastasis, Sulindac
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SulindacDrug
one tablet 150mg twice daily
PlaceboDrug
One tablet twice daily
Validate assays and shipping methodsOther
| Study group | Role | What they receive |
|---|---|---|
| Sulindac | Active comparator | one tablet twice daily Receives: Drug: Sulindac |
| Placebo | Placebo comparator | one tablet twice daily Receives: Drug: Placebo |
| Normal Volunteers (or control group) | Other | Normal volunteers (or control group) enrolled with the only purpose to validate assays and the shipping method. Receives: Other: Validate assays and shipping methods |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Circulating S100A4 Transcript in Patients Receiving Sulindac 150 mg BD (Twice Daily) by Mouth Following Resection of Colorectal Cancer Metastases Compared to Those Who do Not.
Difference in circulating S100A4 transcript levels will be determined by assessing the circulating S100A4 transcript level at initial presentation versus the circulating S100A4 transcript level post resection.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2013 (estimated)
- Study startApr 2013
- Primary completionJan 2015
- Study completionJan 2015
Why it stopped: The trial was prematurely closed due to lack of accrual.
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Collaborators
- Charite University, Berlin, Germany
- Responsible party
- Principal investigator, Marybeth Hughes, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Marybeth S Hughes, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01856322
- Sponsor's protocol ID
- 130126
- Other IDs
- 13-C-0126
- Status last verified
- Oct 2015
- First submitted
- 14 May 2013
- Last updated
- 23 Oct 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Siegel R, Naishadham D, Jemal A. Cancer statistics for Hispanics/Latinos, 2012. CA Cancer J Clin. 2012 Sep-Oct;62(5):283-98. doi: 10.3322/caac.21153.
PubMed 22987332Obrand DI, Gordon PH. Incidence and patterns of recurrence following curative resection for colorectal carcinoma. Dis Colon Rectum. 1997 Jan;40(1):15-24. doi: 10.1007/BF02055676.
PubMed 9102255de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000 Aug;18(16):2938-47. doi: 10.1200/JCO.2000.18.16.2938.
PubMed 10944126
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Prospective Randomized Double Blind Trial Comparing Metastasectomy Plus Sulindac Versus Metastasectomy Alone in Patients With Stage IV Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01856322
- Acronym / sponsor ID
- 130126
- Keywords
- Colorectal Cancer, Liver Metastasis, Sulindac
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was prematurely closed due to lack of accrual.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Collaborators
- Charite University, Berlin, Germany
- Study start
- Apr 2013
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 17 May 2013 (estimated)
- Results
- Posted 7 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Some types of inflammation may increase the risk of cancers in the intestinal track. Because of this possibility, anti-inflammatory drugs may be able to prevent tumor growth and spread. One such drug, sulindac, may be helpful to study. Researchers want to see if people who are having surgery to remove intestinal tumors from advanced colorectal cancer will benefit from sulindac. It will be tested against a placebo.
Objectives:
- To see if sulindac can improve treatment outcomes in people who are having surgery for advanced colorectal cancer.
Eligibility:
- Individuals at least 18 years of age who are having surgery for advanced colorectal cancer.
Design:
- Participants will be screened with a physical exam and medical history. Blood samples will be collected. Imaging studies and heart and lung function tests may also be given.
- Participants will be separated into two groups. One group will take sulindac. The other will take a placebo.
- Participants will take sulindac or placebo twice daily from about 2 to 3 weeks before the scheduled surgery. Seven days before the surgery, they will stop taking the pills.
- Participants will have surgery to remove their tumors. The surgery will also remove affected organ tissue.
- Participants will start to take the pills again once they have recovered from surgery. They will continue taking the sulindac or placebo twice a day for 3 years, or for as long as the tumors do not return.
Detailed description
- Despite strong evidence for a causative role of inflammatory mediators in intestinal cancer, the underlying mechanisms remain obscure. Established evidence indicates activation of the Wnt/beta-catenin pathway is an early step in the malignant transformation of colorectal adenomas with persistent activation in 90% of colorectal cancers. Activation of this pathway ultimately effects transcription of the S100A4 gene.
- S100A4 transcript serum levels have been shown to correlate with risk of recurrence in colorectal cancer and patients with systemic metastases are found to have increased S100A4 transcript expression.
- S100A4 may be a novel prognostic biomarker in colorectal cancer.
- Cyclooxygenase-2 is a key enzyme involved in the inflammatory response and is a key target of molecular chemoprevention in colorectal adenoma prevention trials.
- Recent studies demonstrate mitigation of Wnt/beta-catenin signaling by COX-2 inhibition via administration of the non-steroidal anti-inflammatory drug (NSAID) sulindac using in vitro and in vivo animal models.
- We hypothesize that sulindac administration will abrogate Wnt/beta-catenin mediated signaling and thus decrease S100A4 activity in patients with colorectal metastases.
- We propose to define the benefit of sulindac administration to patients with colorectal metastases following resection and validate the use of circulating S100A4 transcripts as a novel biomarker for disease recurrence.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sulindac | Active comparator | Drug: Sulindacone tablet twice daily |
| Placebo | Placebo comparator | Drug: Placeboone tablet twice daily |
| Normal Volunteers (or control group) | Other | Other: Validate assays and shipping methodsNormal volunteers (or control group) enrolled with the only purpose to validate assays and the shipping method. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age greater than 18
- Able to read and understand the informed consent
- No self-reported co morbidities of history of cancer
Key exclusion criteria (9 listed)
- Women of child-bearing potential who are pregnant or breast feeding because of the potentially dangerous effects of the chemotherapy on the fetus or infant.
- Active systemic infections, coagulation disorders or other major medical illnesses precluding major surgery.
- Patients receiving warfarin anticoagulation, who cannot be transferred to other agents, such as low molecular weight heparins, anti-factor Xa (anti-Xa) agents, etc.
- Active bleeding disorders
- Patients with uncontrolled hypertension (would suggest: systolic blood pressure (SBP)> 155, diastolic blood pressure (DBP)> 90), unstable coronary disease (unstable angina, evidence of congestive heart failure (CHF), or myocardial infarction (MI) within 6-12 months of study)
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 |
|---|---|---|
| Sulindacone tablet 150mg twice daily | Drug | Sulindac |
| PlaceboOne tablet twice daily | Drug | Placebo |
| Validate assays and shipping methods | Other | Normal Volunteers (or control group) |
Primary outcome
Difference in Circulating S100A4 Transcript in Patients Receiving Sulindac 150 mg BD (Twice Daily) by Mouth Following Resection of Colorectal Cancer Metastases Compared to Those Who do Not.
Time frame: 3 years
Difference in circulating S100A4 transcript levels will be determined by assessing the circulating S100A4 transcript level at initial presentation versus the circulating S100A4 transcript level post resection.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22987332Siegel R, Naishadham D, Jemal A. Cancer statistics for Hispanics/Latinos, 2012. CA Cancer J Clin. 2012 Sep-Oct;62(5):283-98. doi: 10.3322/caac.21153.
- Background: PubMed 9102255Obrand DI, Gordon PH. Incidence and patterns of recurrence following curative resection for colorectal carcinoma. Dis Colon Rectum. 1997 Jan;40(1):15-24. doi: 10.1007/BF02055676.
- Background: PubMed 10944126de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000 Aug;18(16):2938-47. doi: 10.1200/JCO.2000.18.16.2938.
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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.
Marybeth S Hughes, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sulindac and Validate assays and shipping methods in people with Colorectal Cancer and Liver Metastasis, run by National Cancer Institute (NCI) at 1 site 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 3 inclusion and 9 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 23 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 7 May 2015). 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?
Difference in Circulating S100A4 Transcript in Patients Receiving Sulindac 150 mg BD (Twice Daily) by Mouth Following Resection of Colorectal Cancer Metastases Compared to Those Who do Not. (time frame: 3 years). 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 NCT01856322, which also lists 3 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 23 Oct 2015.