Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Recurrence

Neoplasm Metastasis

Colonic Neoplasms

Liver Neoplasms

Neoplastic Processes

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Liver Diseases

Hematinics

All Drugs and Chemicals

Platelet Aggregation Inhibitors

Lipid Regulating Agents

Dermatologic Agents

Other Dietary Supplements

Herbal and Botanical

Liver Extracts

Eicosapentaenoic acid ethyl ester

Mineral Oil

Omega 3 Fatty Acid

Cola

Soft gelatin capsules containing 1g pure EPA-EE equivalent to 914mg EPA-FFA. Administered as 4g per day to be taken as 2 capsules in the morning and 2 capsules in the evening.

Soft gelatin capsules containing light mineral oil. 4 capsules to be taken per day (2 in the morning and 2 in the evening).

Composition: soft amber to light yellow, oblong gelatin capsules. One capsule contains 1g pure EPA-EE Dose: 4 capsules per day

Icosapent Ethyl

Composition: soft, amber to light yellow, oblong gelatin capsules containing light mineral oil:

Dose: 4 capsules per day

Placebo

Mark Hull

A significant proportion of patients who undergo liver surgery to remove bowel cancer that has spread to the liver (metastases) develop disease recurrence and die from the disease. A previous small study (the EMT study) suggested a possible survival benefit in patients who took the naturally-occurring omega-3 fatty acid EPA (a fish oil supplement) before liver surgery. The EMT2 study is a larger study which will recruit 448 men and women with liver metastases from bowel cancer. Trial participants will receive either Icosapent Ethyl (pure EPA derived from fish oil) or placebo (dummy capsules). EMT2 will investigate whether patients who take this supplement before liver surgery and for up to four years after surgery, remain free of recurrence for longer than those who take placebo (dummy capsules)

Despite significant advances in diagnosis and treatment of colorectal cancer (CRC), it remains the second most common cause of cancer-related death in the UK. The majority of deaths from CRC are related to distant metastasis, predominantly to the liver. Overall 5-year survival following liver resection and adjuvant chemotherapy for colorectal cancer liver metastases (CRCLM) is, at best, 40-60%. Despite surgery with curative intent, up to 60% of patients develop recurrence within 2 years of surgery. The preliminary EMT study was a Phase II RCT of EPA 2 g daily in patients (n=88) undergoing liver resection surgery for CRCLM. Although there was no difference in the primary endpoint (tumour proliferation index), metastases from the EPA arm had a lower vascularity score (suggesting possible anti-angiogenic activity) than placebo-treated tumours. Although EPA (or placebo) treatment was limited to the pre-operative period, overall survival (OS) and disease-free survival (DFS) were specified as exploratory end-points on the basis that oral dosing with EPA before liver surgery would provide tissue EPA exposure in the immediate peri-operative period with prolonged bioavailability in the post-operative period due to the slow tissue 'washout' kinetics of EPA. Survival analysis demonstrated that the median DFS in the EPA group was 22.6 months compared with 14.7 months in the placebo group. Any DFS benefit was explained by a reduction in CRC recurrence from 12 months after surgery onwards.

The EMT2 study is a randomised, double-blind, placebo-controlled, multi-centre, phase III trial of the omega-3 fatty acid (O3FA) eicosapentaenoic acid (EPA) as the ethyl ester (icosapent ethyl \[IPE; Vascepa®\]) in patients undergoing liver resection surgery for colorectal cancer liver metastasis (CRCLM) with curative intent designed to determine whether EPA treatment improves Progression-Free Survival (PFS). A key secondary objective is overall survival (OS).

Investigators will recruit adult individuals listed for CRCLM resection with curative intent.

Randomisation will be 1:1 to receive either IPE capsules or placebo capsules. 4 capsules per day containing IPE (equivalent to 4 g EPA-ethyl ester \[EE\] daily) or 4 placebo capsules per day. Participants will start treatment a prior to CRCLM surgery and will continue to receive treatment for a minimum of 2 years and a maximum of 4 years post-liver resection. Participants are followed up for 60 days beyond the end of treatment.

Participants are clinically assessed 6 months post-operatively (from liver resection) and at 6-monthly intervals thereafter for disease progression/recurrence.

EPA for Metastasis Trial 2

A Randomised Placebo-controlled Phase III Trial of the Effect of the Omega-3 Fatty Acid Eicosapentaenoic Acid (EPA) on Colorectal Cancer Recurrence and Survival After Surgery for Resectable Liver Metastases

The datasets generated during the current study will be available upon request from the Clinical Trials Research Unit at the University of Leeds.

De-identified individual participant data datasets generated during the current study will be available upon request from the Clinical Trials Research Unit, University of Leeds (contact CTRU-DataAccess@leeds.ac.uk in the first instance).

EPA content measured at baseline, surgery and 6 months after surgery. Samples taken at selected sites only

Change in lean body mass measured by CT scanning during follow-up as assessed by the L3 skeletal muscle index score. Scans reviewed from selected sites only

PFS is defined as the time from randomisation to death (from any cause), first documented evidence of disease progression, new recurrence or clinical deterioration unequivocally due to disease progression

The time from randomisation to death, from any cause (key secondary endpoint)

The number of participants with treatment-emergent adverse events as defined by CTCAE v4.0

Measured using the EORTC QLQ-C30 questionnaire

Measured using the QLQ-LMC21 questionnaire

Excluding DCIS, cervical carcinoma in situ, superficial bladder carcinoma where treatment consisted of resection only and non-melanoma skin cancer where treatment consisted of resection or radiotherapy only)

Yorkshire Cancer Research

Amarin Pharma Inc.

Mark A Hull, PhD FRCP

Prof Mark Hull

Skin and Connective Tissue Diseases

Rare Diseases

Breast Neoplasms

Carcinoma

Inflammatory Breast Neoplasms

Breast Diseases

Skin Diseases

Inflammatory Breast Cancer

Antineoplastic Agents

Amino Acids

Dasatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive icosapent ethyl PO BID and dasatinib PO QD in each treatment cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Naoto T Ueno

This phase Ib/II tests the safety, side effects, and best dose of icosapent ethyl in combination with dasatinib and whether they work to shrink tumors in patients with triple-negative inflammatory breast cancer that has spread to other places in the body (metastatic). Triple-negative inflammatory breast cancer is a type of inflammatory breast cancer in which the tumor cells do not have estrogen receptors, progesterone receptors, or large amounts of HER2/neu protein on their surface. Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Icosapent ethyl is an omega-3 fatty acid and in a class of medications called antilipemic or lipid-regulating agents. It may decrease the amount of triglycerides and other fats made in the liver. Preclinical studies have suggested that it may reduce the growth of triple negative inflammatory breast cancer cells. Combination therapy with dasatinib and icosapent ethyl may help shrink tumors in patients with triple-negative inflammatory breast cancer.

PRIMARY OBJECTIVES:

I. To determine maximum tolerated dose (MTD) of icosapent ethyl (EPA) and dasatinib in patients with metastatic triple negative inflammatory breast cancer (mTN-IBC). (Phase 1b) II. To determine the overall response rate (ORR) of EPA and dasatinib therapy in patients with mTN-IBC. (Phase 2)

SECONDARY OBJECTIVES:

I. To determine the clinical benefit rate (CBR) of EPA and dasatinib therapy in patients with mTN-IBC.

II. To determine progression-free survival (PFS) at 1 year for patients with mTN-IBC who were enrolled in the study and received EPA and dasatinib therapy.

III. To determine overall survival (OS) at 2 years for patients with mTN-IBC who were enrolled in the study and received EPA and dasatinib therapy.

IV. To determine the induction of apoptosis by EPA and dasatinib therapy.

EXPLORATORY OBJECTIVES:

I. To determine the effect of EPA and dasatinib therapy on the expression of cholesterol transporter.

II. To determine the relationship between the expression of EphA2 and the treatment response to EPA and dasatinib therapy.

III. To determine the change in Ki67 by EPA and dasatinib therapy. IV. To evaluate the change in cholesterol homeostasis and tumor membrane rigidity after EPA and dasatinib therapy.

V. To investigate the effect of EPA and dasatinib therapy on the systemic inflammation.

OUTLINE: This is a phase Ib dose-escalation study of icosapent ethyl in combination with fixed dose dasatinib, followed by a phase II study.

Patients receive icosapent ethyl orally (PO) twice daily (BID) and dasatinib PO once daily (QD) in each treatment cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of the study treatment, patients will undergo in-clinic post-treatment evaluations 1 month after their last study treatment or before starting new treatment, whichever occurs first, subsequently, patients are followed every 3 months for 2 years.

Testing an Omega-3 Fatty Acid-Based Anti-Cancer Therapy for Patients With Triple-Negative Inflammatory Breast Cancer That Has Spread to Other Parts of the Body

Phase Ib/II Study of EPA-Based EphA2 Targeted Therapy for Patients With Metastatic Triple-Negative Inflammatory Breast Cancer

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

ABCA1 will be measured not only in tumor cells but also in immune cells, especially in M1 and M2 macrophages since ABCA1 is known to promote cholesterol efflux in macrophages. The intensity of the staining and percentage of stained cells will be scored by H-score following the formula: H Score = summation (1+i) pi, where i is the intensity score and pi is the percentage of cells with that intensity. H-score will be analyzed using descriptive statistics, including mean, standard deviation and 95% confidence interval.

EphA2-immunohistochemistry (IHC) positivity will be defined from 0 to 3+ by modifying the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) HER2 testing clinical practice guideline. After the completion of the phase 2 part, the association between 3 levels of EphA2-IHC expression (negative, equivocal, and positive) and ORR will be analyzed using Fisher's exact test and logistic regression.

Will be assessed and analyzed using descriptive statistics. Continuous value before/after treatment will be compared by utilizing the Wilcoxon signed-rank test and paired t-test.

MTD is selected based on isotonic regression. Specifically, the dose is selected as the MTD for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate. If there are ties, the higher dose level is selected when the isotonic estimate is lower than the target toxicity rate; the lower dose level is selected when the isotonic estimate is greater than or equal to the target toxicity rate.

Will be the proportion of the patients with static disease (SD) \>= 24 weeks, complete response (CR), and partial response (PR). CBR will be estimated along with a 95% exact confidence interval.

Defined as the rate of patients without the progression of disease or loss to follow-up at 1 year after initiating the EPA and dastinib combination therapy. Will be estimated using the methods of Kaplan and Meier.

Defined as the survival rate at 2 years after initiating the EPA and dasatinib combination therapy. Will be estimated using the methods of Kaplan and Meier.

Tumor apoptosis will be measured by using the Luminex Apoptosis multiplex immunoassay panel (cleaved caspase-3) as well as TdT-Mediated dUTP Nick End Labeling (TUNEL) assay.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
EPA for Metastasis Trial 2	NCT03428477	Liver Metastasi... Colon Cancer	Icosapent Ethyl Placebo	18 Years -	University of Leeds
Testing an Omega-3 Fatty Acid-Based Anti-Cancer Therapy for Patients With Triple-Negative Inflammatory Breast Cancer That Has Spread to Other Parts of the Body	NCT05198843	Anatomic Stage ... Metastatic Trip...	Dasatinib Icosapent Ethyl	18 Years -	National Cancer Institute (NCI)
Testing an Omega-3 Fatty Acid-Based Anti-Cancer Therapy for Patients With Triple-Negative Inflammatory Breast Cancer That Has Spread to Other Parts of the Body	NCT05198843	Anatomic Stage ... Metastatic Trip...	Dasatinib Icosapent Ethyl	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for icosapent ethyl