Surgery Plus Sulindac or Surgery Alone for Advanced Colorectal Cancer

NCT01856322 | Terminated Phase 2 Results

• 2 other identifiers: 13012613-C-0126
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Colorectal Cancer; Liver Metastasis; Colorectal Adenocarcinoma

Keywords

Colorectal Cancer; Liver Metastasis; Sulindac

Outcome Measures

Primary Outcomes (1)

• 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.

  3 years

Study Arms (3)

Sulindac

ACTIVE COMPARATOR

one tablet twice daily

Drug: Sulindac

Placebo

PLACEBO COMPARATOR

one tablet twice daily

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.

Other: Validate assays and shipping methods

Interventions

Sulindac DRUG

one tablet 150mg twice daily

Sulindac

Placebo DRUG

One tablet twice daily

Placebo

Validate assays and shipping methods OTHER

Normal Volunteers (or control group)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed colorectal adenocarcinoma with metastatic disease confined to the liver, or limited extrahepatic intra-abdominal disease Note: limited sites of disease include:
• porta hepatis lymph node metastases
• pelvic lymph node metastases (internal iliac, external iliac or obturator)
• Hepatic and intra-abdominal metastases must be measurable by computed tomography (CT), magnetic resonance imaging (MRI) and/or positron emission tomography (PET) scan
• Liver disease must be amenable to gross total resection (R0/R1) with adequate functional liver remnant which requires preservation of at least 2 contiguous hepatic segments with adequate inflow, outflow, and biliary drainage with a functional liver remnant (FLR) volume of more than 20% (for healthy liver)
• Greater than or equal to 18 years of age.
• Must be able to understand and sign the Informed Consent Documentation.
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) less than or equal to 2.
• Life expectancy of greater than six months.
• Patients of both genders must be willing to practice birth control during and for one week after taking sulindac/placebo.
• Hematology:
• Absolute neutrophil count greater than 1500/mm\^3 without the support of Filgrastim.
• Platelet count greater than 75,000/mm\^3.
• Hemoglobin greater than 8.0 g/dl.
• Chemistry:

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Charite University, Berlin, Germany: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 22987332 BACKGROUND

• Obrand 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.

  PMID: 9102255 BACKGROUND

• de 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.

  PMID: 10944126 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Sulindac

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Marybeth Hughes
• Organization: National Cancer Institute

hughesm@mail.nih.gov

301-594-9341

Study Officials

• Marybeth S Hughes, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 14, 2013
• First Posted: May 17, 2013
• Study Start: April 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: October 23, 2015
• Results First Posted: May 7, 2015

Record last verified: 2015-10

Locations

US (1)