Neoplasms

Digestive System Diseases

All Conditions

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Hypoglycemic Agents

All Drugs and Chemicals

Antipyretics

Anti-Inflammatory Agents

Antirheumatic Agents

Fibrinolytic Agents

Analgesics

Platelet Aggregation Inhibitors

Metformin

Aspirin

placebo Aspirin (1 tablet daily) + placebo Metformin (1 tablet BID) for 12 months

placebo Aspirin (1 tablet daily) + active Metformin (850 mg, 1 tablet BID), for 12 months

active Aspirin (100 mg, 1 tablet daily) + placebo Metformin (1 tablet BID), for 12 months

active Asprin (100 mg, 1 tablet daily) + active Metformin (850 mg, 1 tablet BID), for 12 months

Arm C (experimental arm) Treatment: active ASA + placebo MET Dose: 100 mg, 1 tablet daily + 1 tablet twice a day (BID) Duration: 12 months

Arm B (experimental arm) Treatment: placebo ASA + active MET Dose: 1 tablet daily+ 850 mg, 1 tablet twice a day (BID) Duration: 12 months

Arm A (control arm) Treatment: placebo ASA + placebo MET Doses: 1 tablet daily +1 tablet twice a day (BID) Duration: 12 months

Placebo

Andrea De Censi, MD

It has been shown that Aspirin (ASA) as well as Metformin (Met) can inhibit the incidence and mortality of colorectal cancer (CRC). In this randomized, placebo controlled clinical trial we compare the effect of these two drugs alone and their combination to prevent recurrent CRC after surgery.

Epidemiological studies and cardiovascular prevention trials have shown that low-dose aspirin (ASA) can inhibit colorectal cancer (CRC) incidence and mortality, including inhibition of distant metastases. Metformin (MET) has also been associated with decreased CRC incidence and mortality in meta-analyses of epidemiological studies in diabetics and has been shown to decrease by 40% colorectal adenoma recurrence in a randomized trial. Recent studies have shown that ASA is an inhibitor of mTOR/S6K1 and an activator of AMPK, targeting regulators of intracellular energy homeostasis and metabolism, and that the combination of ASA and MET, another AMPK activator and S6K1 inhibitor, has a striking additive effect on AMPK activation and mTOR inhibition, with increased autophagy and decreased cell growth in CRC cell lines. While both drugs are being tested as single agents, their combination has not been tested in trials.

This is a randomized, placebo-controlled, double blind, 2x2 biomarker trial of ASA and MET to test the activity of either agent alone and the potential synergism of their combination on a set of surrogate biomarkers of colorectal carcinogenesis. After surgery 160 patients with stage I-III colon cancer will randomly be assigned in a four-arm trial to either ASA, 100 mg day, MET 850 mg bid, their combination, or placebo for one year. The primary endpoint biomarker is the change, defined as the difference between pre- and post-treatment expression of nuclear factor kappa-B (NFκB), in the unaffected mucosa of proximal and distal colon obtained by multiple biopsies in two paired colonoscopies one year apart. Additional biomarkers will include: 1) the genomic profile of candidate genes, pathways, and overall genomic patterns in tissue biopsies by genome wide gene expression arrays; 2) the IHC expression of tissue pS6K, p53, beta-catenin, PI3K; 3) the associations of mutations and SNPs with treatment response by next generation sequencing of primary tumors; 4) the measurement of circulating IL-6, CRP and VEGF and 5) plasma and colonic MET concentrations and their correlation with biomarker profiles.

A Randomized, 2x2 Factorial Design Biomarker Prevention Trial of Low-dose ASA and Metformin in Stage I-III Crc Patients

A Randomized, Phase II, Double-blind, Placebo-controlled, Multicenter, 2x2 Factorial Design Biomarker Tertiary Prevention Trial of Low-dose Aspirin and Metformin in Stage I-III Colorectal Cancer Patients. The ASAMET Trial

It will be measured the change, defined as the difference between post- and pre-treatment levels, in NFκB expression in normal colonic tissue. The NFκB transcription factor family is composed of the p65, RelB, c-Rel, p105, andt p100 subunits, and activation of the NFκB pathway is defined by the nuclear translocation of the p65 subunit. Therefore, cytoplasmic and nuclear localization of p65 will be immunohistochemically assessed as an indicator of NFκB activity. The analysis of expression will be performed by semi quantitative assessment: NFκB expression will be measured primarily as the percentage of positive nuclear areas for NFkB over the total nuclear areas in 10 section fields.

It will be measured the change (defined as above) in IHC expression levels of pS6K, p53, beta-catenin, PI3K (from colon unaffected biopsy specimen). These biomarkers will be measured as described above for NFκB.

The change in circulating biomarkers IL-6, CRP, VEGF and HOMA index\[homeostasis model assessment (fasting blood glucose (mmol/L)\*insulin (mU/L))/22.5\] will be measured in plasma and serum at two time points, pre- and post-intervention, using monoclonal ELISA kits.

Gene expression levels of candidate genes and pathways, in normal colonic tissue, will be measured on a genome-wide basis using Illumina HumanHT-12 Expression BeadChips targeting more than 47,000 transcripts including known splice variants across the human transcriptome.

The blood and tissue MET levels will be measured. LC-MS/MS system will be used for the drug level determinations to be correlated with biomarker modulation and toxicity

Ente Ospedaliero Ospedali Galliera

Principal Investigator

Heart and Blood Diseases

Blood and Lymph Conditions

Rare Diseases

Thrombosis

Polycythemia Vera

Polycythemia

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Bone Marrow Diseases

Myeloproliferative Disorders

Chronic Myeloproliferative Disorders

Pharmaceutical Solutions

Anti-Infective Agents

Antineoplastic Agents

Central Nervous System Depressants

Other Dietary Supplements

Amino Acids

Interferons

Benzocaine

Interferon-alpha

Interferon alpha-2

Antiviral Agents

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Tannic Acid

Proline

Conventional treatment based on phlebotomies and low dose (100 mg) of acetylsalicylic acid (ASA)

Conventional treatment based on phlebotomies, low dose (100 mg) of acetylsalicylic acid (ASA) plus the addition of 100 µg of Pegylated Proline-Interferon alpha-2b (AOP2014) once every 14 days (subcutaneously).

AOP2014 will be supplied to the patients as pre-filled auto-injection pens, containing 250 µg of active drug (0.5 ml solution for injection). One pen may be used twice within a time period of 4 weeks. Hence investigators will provide one prefilled pen at every monthly visit. AOP2014 will be self-injected subcutaneously by patients once every 14 days at the single doses of 100 µg (0.2 ml).

AOP2014

According to current common clinical practice the regimen must be selected accordingly to maintain the recommended level of HCT\< 45%. Once normalization of the hematocrit has been achieved, blood counts at regular intervals (every 4 weeks) will establish the frequency of future phlebotomies. Sufficient blood should be removed to maintain the hematocrit below 45%.

Phlebotomies

100 mg/daily of ASA is recommended (when there are not contraindications) according with current guidelines for this risk class of patients

Tiziano Barbui, Professor

The Low-PV study is a multicenter, phase II, randomized trial aimed to assess whether the addition of Pegylated Proline-interferon-alpha-2b to the best therapeutic current strategy available based on phlebotomies and low dose acetylsalicylic acid (ASA) could improve the efficacy of treatment of patients with PV at low risk of thrombosis (younger than 60 years and without prior vascular events), in term of control of recommended level of hematocrit \< 45%, over a period of 12 months.

It is an independent, investigator-generated, pragmatic trial including adult PV patients (aged 18-60) diagnosed according to World Health Organization 2008 criteria within the last 3 years before inclusion, without history of thrombosis and younger than 60 years ('low risk' patients).

Eligible patients are randomized to be treated with the best available therapy (recommended for this risk class, standard arm) based on phlebotomy including administration of low-dose (100 mg/daily) of acetylsalicylic acid (ASA, when there are not contraindications) OR Pegylated Proline-Interferon alpha-2b (AOP2014) every 2 weeks in addition to the recommended available regimen (experimental arm), for up to 12 months. The allocation of patients to study arms is 1:1 and stratification at randomization will be performed according to age category (\< 50 years old or \> 50 years old) and time from diagnosis (naϊve or non-naϊve). Naive patients are defined as new cases coming to observation, diagnosed for the first time just before study entry and never treated; non-naive patients are old cases (diagnosis not older than 3 years before study entry) undergoing therapy with phlebotomy and/or low doses of ASA.

Primary endpoint (PEp) is defined by the proportion (%) of patients who maintain the median value of hematocrit (HCT) below 45% during 12 months of treatment in each arm, without progression of disease and no need of any extra-protocol cytoreductive drug (responder patients).

Secondary endpoints include evaluation of hematological and molecular response, histological remission and safety profile of the protocol therapy.

Before randomization all patients undergo phlebotomies in order to reach an HCT below 45%.

After randomization, according to current common clinical practice the regimen of phlebotomies must be selected accordingly to maintain the recommended level of HCT\< 45%. Once normalization of the HCT has been achieved, blood counts at regular intervals (every 4 weeks) will establish the frequency of future phlebotomies. Sufficient blood is recommended to be removed in order maintain the hematocrit below 45%. Supplemental iron therapy should not be administered.

All patients receive low-dose of ASA (100 mg/daily) as recommended by the current guidelines for low-risk subjects with PV.

Patients allocated in the experimental group receive in addition a pre-filled auto-injection pen for the subcutaneous auto-administration (into the abdominal skin or the thigh) of 100 µg of Pegylated Proline-Interferon alpha-2b (AOP2014) once every 14 days.

Patient visits are scheduled every month (4 weeks) for 12 months to assess and perform a reliable calculation of the primary end-point (% of patients with median HCT levels \<45%).

At each monthly visit a pre-filled auto-injection pen is delivered to the patients who have been randomized in the experimental arm.

Assuming an expected drop-out rate of 12%, a total sample size of 150 patients (75 randomized in each group) will be randomized to reject the null hypothesis that the proportion of patients achieving the primary endpoint is 50% in favor of the alternative hypothesis that this proportion is 75% when AOP2014 is added to the phlebotomy based- therapy, with a power of 80% and an alpha error of 0.05 (two-tailed).

Two interim-analysis are planned when 50 and 100 of randomized patients have completed the 12 months study, respectively, in order to evaluate and supervise both safety and primary endpoint. The Lan and DeMets (1983) spending function with O'Brien-Fleming type boundaries will be employed to preserve the overall two-sided type I error rate for effectiveness at the 0.05 level, regardless of the timing of the analysis.

The results of the second interim analysis carried out at in April 2020 indicated a significant higher efficacy of the experimental arm than standard arm. The composite primary end-point was reached in 84% in patients of Ropeginterferon arm vs. 60% in standard arm (p=0.008, Odds Ratio=3.5, 95% CI: 1.3-10.4). This result, according to the statistical evaluation for futility and efficacy, reveals that , the null hypothesis is already been proven with first 100 patients randomized and cannot change in the future when 150 patients will enter the study. Therefore the data safety monitoring board and the steering committee agree that the accrual of new patients can be interrupted with 127 patients included.

The primary endpoint assessment is performed after the completion of the first 12 months of therapy for all subjects enrolled ('core study').

A period of 12 months is expected for completion of the enrolment / randomization phase. The 'core study' itself will take 12 months of treatment per patient.

Based on results from the 'core study' the extension phase will continue as follows:

1. After 12 month patients who meet the primary endpoint following either conventional or experimental therapy will enter the extension phase and remain on their current regimen.
2. non-responders, not meeting the primary endpoint after 12 months of conventional therapy will be switched to the experimental treatment.
3. non-responder, not meeting the primary endpoint after 12 months of experimental therapy will be switched to conventional treatment.

This extension phase will last for another 12 months from the Last Visit Last Patient included (LVLP) into the core study (matching cases 1 and 2 as defined above). Based on this, the overall length of the study is expected to cover a period of 36 months from the First Patient Included (FPI).

The Benefit/Risk Profile of AOP2014 in Low-risk Patients With PV

The Benefit/Risk Profile of Pegylated Proline-Interferon Alpha-2b (AOP2014) Added to the Best Available Strategy Based on Phlebotomies in Low-risk Patients With Polycythemia Vera (PV). The Low-PV Randomized Trial

No plan has been defined yet about sharing of IPD

Impact of PV and therapy on subjects will be evaluated through assessment of symptoms burden using Functional Assessment of cancer Therapy-Anaemia (FACT-An) and Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) questionnaires, that will be administered to subjects trimonthly

For each patient the median value of HCT percentage will be calculated from all measurements detected and reported every month (from baseline to 12-month visit or study end). A patient will be defined as responder (achieving PEp) when he maintains the median value of HCT \< 45%, after undergoing treatments according to this protocol, for up 12 months.

A patient will be defined as non-responder (not achieving PEp) when

1. Does not maintain the median value of HCT \< 45%, after undergoing treatments according to this protocol, for up 12 months, or
2. Is in need of any additional chemotherapeutic and/or cytoreductive treatment aimed to manage disease due to disease progression.

1. The total number of phlebotomies will be calculated for each patients during 12 months of therapy (and then 24 months);
2. Based on values obtained from point (1) in each arm-group of patients, the median number of phlebotomies performed in each therapy group will be calculated (and compared) after 12 and 24 months of therapy (or completion of the study)

For each patient the median value of HCT (%), absolute white blood cells (WBCs) count and absolute platelets (PLTs) count will be calculated from all measurements detected and reported at least every month (from baseline to 12-month visit and then to 24-month visit/study completion). A patient will be defined as achieving hematological response when the median values of HCT \< 45%, WBCs count \< 10 x10\*9/L and PLTs count \< 400 x10\*9/L is observed after 12 months of therapy (or 24 months). The proportion of patients who maintains this response after 24 months (or study completion) will be calculated (and compared) in each arm.

The proportion (rate per cent) of patients with not palpable spleen will be calculated in each arm as the ratio of number of patients with resolution of splenomegaly or persistence of not palpable spleen at palpation with respect to baseline, on number of patients randomized in each arm, after 12 and 24 months (study completion) of therapy, per cent.

Quantitative Janus kinase-2 measurements (central lab facility) will be performed at baseline and after 12 months of therapy for all patients; Janus kinase-2 assessment will be performed also after 24 months for patients receiving interferon (experimental therapy). Reduction of allele burden in each patient (with respect to baseline) will be assessed according to Jovanovic et al, Leukemia 2013.

The proportion (rate per cent) of patients with Janus kinase-2 allele burden reduction or remission will be calculated in each arm (and compared).

Defined as presence of age-adjusted normocellularity and disappearance of trilinear hyperplasia, and absence of \>grade 1 reticulin fibrosis. It will be assessed in each patient and then the proportion (rate per cent) of patients with bone marrow histological remission will be calculated in each arm (and compared).

The number of events will be recorded any time during the study in order to assess the frequency ,every 12 months and at completion of the study, and their incidence in each arm and whole population. Comparison between arms will be performed.

Incidence, causality and intensity of clinical relevant adverse events will be assessed in each arm and compared all over the study.

The rate of assigned treatment withdrawal due to any protocol drug-related toxicity occurred any time will be compared. Number of adverse events, expressed as frequency in each arm, will be calculated (as ratio of number of patient experiencing adverse on the the number of patients randomized in each arm) and compared

AOP Orphan Pharmaceuticals AG

FROM- Fondazione per la Ricerca Ospedale di Bergamo- ETS

Immune System Diseases

Symptoms and General Pathology

Multiple Myeloma

Neoplasms, Plasma Cell

Thromboembolism

Disease Progression

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anticoagulants

Lenalidomide

Rivaroxaban

Factor Xa Inhibitors

Antithrombins

Antithrombin III

Protease Inhibitors

Serine Proteinase Inhibitors

HIV Protease Inhibitors

Serine

Patients with MM will receive Len-Dex combination and Rivaroxaban (10 mg) daily

Patients MM will receive Len-Dex combination and ASA 81 mg daily

Martha Louzada, MD

The intended study is designed as a a phase IV pragmatic multicenter randomized controlled clinical trial, comparing the impact of two different therapies including ASA vs. Rivaroxaban in newly diagnosed or relapsed and refractory multiple myeloma patients treated with Lenalidomide Dexamethasone (Len-Dex) combination therapy. The pilot feasibility study was conducted in preparation for this randomized controlled trial designed to assess the effect of an intervention.

RithMM is a phase IV, pragmatic, multicenter, open label Canadian trial. The study started with a pilot feasibility phase where 3 centres (London, Ottawa and Halifax) enrolled 34 patients within 12 months. Utilizing a roll-over design, the full RithMM trial will require a total of 304 patients to demonstrate that rivaroxaban 10 mg daily for 6 months is superior to ASA 81 mg daily for 6 months in preventing any thromboembolic events in newly diagnosed myeloma (NDMM) and relapsed/refractory (RRMM) patients on Len-Dex -based therapy. The study will require 8 participating centres in order to be able to achieve our recruitment goal within 12 to 18 months. Patients with NDMM or RRMM receiving Len-Dex based combination therapy with or without combination with other anti-myeloma drugs will be assessed for eligibility to be enrolled in the study. The research team intends to rollover the participants of our feasibility study into this current full randomized control trial comparing the efficacy outcome for the RithMM trial is the overall incidence of cardiovascular events, which includes arterial or venous thromboembolic events.

By conducting this trial, the investigators plan to externally validate the International Myeloma Working Group (IMWG) criteria model for thromboembolic risk by assessing the relevance of measuring pre-specified myeloma and thrombosis activity biomarkers (D-Dimer, beta-2 microglobulin, C-reactive protein (CRP), LDH) at every follow-up visit and their potential association with thromboembolism (TE) risk.

Rivaroxaban or Aspirin As Thromboprophylaxis in Multiple Myeloma

Rivaroxaban for Improvement of Thromboembolism Outcomes in Patients With Multiple Myeloma on Lenalidomide-based Therapy: RithMM Trial

At each visit, patients will be asked standardized questions to capture the presence of primary. During these interviews the study coordinator will collect data related to resource utilization (e.g. health care services use) and ask whether the patient had a diagnosis of VTE, ATE or a bleeding event during this period. Any hospital or medical office encounters associated to any of the above-mentioned complaints will be checked and any test or procedures done will be recorded (e.g; echocardiogram, ECG, CT scan, MRI, transfusion).

Frequency and severity of adverse events and serious AEs based on hospital admission and patient-self reporting events

Subgroup analysis stratifying patients into low and high risk of thromboembolic events to assess any potential difference in the efficacy and safety outcomes.

The bio-markers are: D-dimer, LDH, B2 microglobulin and C-reactive protein (CRP) will be collected

The Ottawa Hospital

Dalhousie University

Niagara Health System

Hamilton Health Sciences Corporation

Lawson Health Research Institute

Hemorrhage

Gastrointestinal Hemorrhage

Polyps

Rectal Diseases

Herbal and Botanical

Cola

Patients with at least one large polyps taking aspirin in dose 75 mg daily for 21 days (7 days before and 14 days after polypectomy)

Patients with at least one large polyps taking placebo daily for 21 days (7 days before and 14 days after polypectomy)

Usage or withdrawal of aspirin (75mg daily per os) 7 days before and 14 days after polypectomy

Aspirin (ASA)

Kaminski F Michal, MD

Pisera Malgorzata, MSc

Regula Jaroslaw, MD PhD

The risk of bleeding after polypectomy of large colorectal polyps in patients taking aspirin is uncertain. This is a randomized, multi-center, placebo-controlled, double-blind study to compare the risk of significant bleeding after endoscopic polypectomy of large (\>=10mm) colorectal polyps in patients continuing or discontinuing on daily acetylsalicylic acid (ASA) use. Eligible patients will be randomly assigned in a 1:1 ratio to a group taking 75mg daily ASA or placebo 7 days before and 14 days following polypectomy. The primary endpoint of the study is bleeding within 30 days from colorectal polypectomy. The secondary endpoints are composite cardiovascular events occurring between the date of randomization and 30 days after polypectomy.

Patients chronically taking aspirin (in prophylaxis doses 75-325 mg), with a diagnosis of colorectal polyps ≥ 10 mm in diameter will be enrolled on a routine polypectomy under hospitalization. Meeting the inclusion criteria, after informed consent and a cardiologist consent the patient will receive aspirin/placebo, and The Patient Diary to fill (Visit 1). The patient will be admitted to the Study Center in 6-7 days taking on the aspirin/placebo and prepared for the study (Visit 2). Patient will be under the care of a physician after polypectomy by a minimum of 6 hours. 14 days after polypectomy will be the first control visit, during which the physician will take back patient diary and pack treatment (Visit 3). 30 days after polypectomy will be the second control visit by phone (Visit 4). Patients will be monitored by looking at the end points.

The Risk of Bleeding After Removal of Large Colorectal Polyps in Patients Taking Aspirin

The Risk of Bleeding After Removal of Large Colorectal Polyps in Patients Continuing or Discontinuing on Aspirin: a Multicenter, Double-blind, Placebo-controlled, Randomized Clinical Trial

Clinically significant bleeding after polypectomy - any extravasation of blood from the polypectomy site \[immediate (30s after polypectomy), early (to 24ha after polypectomy) or delayed (24ha to 30 days after polypectomy)\], with clinical and/or endoscopic and/or laboratory (Hb decline by more than 3 g%)symptoms and would require endoscopic intervention and/or surgical and/or blood transfusions;

Composite cardiovascular events - acute coronary syndrome, transient ischemic attack (TIA)or stroke

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Randomized, 2x2 Factorial Design Biomarker Prevention Trial of Low-dose ASA and Metformin in Stage I-III Crc Patients	NCT03047837	Tertiary Preven...	ASA MET Placebo	18 Years - 80 Years	Ente Ospedaliero Ospedali Galliera
The Benefit/Risk Profile of AOP2014 in Low-risk Patients With PV	NCT03003325	Polycythemia Ve...	AOP2014 Phlebotomies ASA	18 Years - 60 Years	FROM- Fondazione per la Ricerca Ospedale di Bergamo- ETS
The Benefit/Risk Profile of AOP2014 in Low-risk Patients With PV	NCT03003325	Polycythemia Ve...	AOP2014 Phlebotomies ASA	18 Years - 60 Years	FROM- Fondazione per la Ricerca Ospedale di Bergamo- ETS
Rivaroxaban or Aspirin As Thromboprophylaxis in Multiple Myeloma	NCT03428373	Multiple Myelom... Multiple Myelom... Multiple Myelom... Multiple Myelom... Multiple Myelom... Multiple Myelom...	Rivaroxaban ASA	18 Years - 90 Years	Lawson Health Research Institute
Rivaroxaban or Aspirin As Thromboprophylaxis in Multiple Myeloma	NCT03428373	Multiple Myelom... Multiple Myelom... Multiple Myelom... Multiple Myelom... Multiple Myelom... Multiple Myelom...	Rivaroxaban ASA	18 Years - 90 Years	Lawson Health Research Institute
The Risk of Bleeding After Removal of Large Colorectal Polyps in Patients Taking Aspirin	NCT01549418	Gastrointestina...	Aspirin (ASA) Placebo	40 Years -	Maria Sklodowska-Curie National Research Institute of Oncology

Spots Global Cancer Trial Database for asa

Every month we try and update this database with for asa cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for asa

Every month we try and update this database with for asa cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for asa cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.