Heart and Blood Diseases

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Thrombosis

Pulmonary Embolism

Embolism

Body Weight

Thromboembolism

Venous Thromboembolism

Venous Thrombosis

Embolism and Thrombosis

Vascular Diseases

Lung Diseases

Respiratory Tract Diseases

Fibrinolytic Agents

Anticoagulants

All Drugs and Chemicals

Heparin

Enoxaparin

Calcium heparin

Heparin, Low-Molecular-Weight

Tinzaparin

Dalteparin

Enoxaparin sodium

Continue low molecular weight heparin (LMWH) at treatment dose according to body weight for further six months.

Discontinue low molecular weight heparin (LMWH) once patient has received six months treatment following index VTE case.

Participants randomised to Arm A will have already received LMWH (Fragmin®), tinzaparin (Innohep®) or enoxaparin (Clexane®) at treatment dose for six months off trial, and should continue the same drug at the same dose for a further six months on trial. No dose alterations are required unless clinically indicated.

Low Molecular Weight Heparin (LMWH)

Simon Noble, Dr

This is a two year, multicentre, mixed methods feasibility study including a randomised controlled two-arm interventional trial, a nested qualitative study, focus groups and a United Kingdom (UK) wide survey exercise.

Venous thromboembolism (VTE) is a term to describe blood clots in the legs known as a deep vein thrombus (DVT) or lung, known as a pulmonary embolus (PE). It is a common condition, which causes many symptoms including leg pain, swelling, chest pain and breathlessness. At its most serious, VTE may lead to sudden collapse and death.

Treating VTE costs the UK National Health Service (NHS) £640 million every year, including the long-term complications experienced by nearly a third of patients. VTE treatment usually consists of three to six months blood thinning medicine known as an anticoagulant. For most patients, a tablet called warfarin is used, which requires regular blood tests to ensure the blood is adequately and safely thinned.

We also know that VTE is particularly common in cancer. In the UK, over 250,000 people are diagnosed each year with cancer, of which nearly a fifth will develop VTE. Warfarin is a potentially risky treatment in cancer patients because it may increase the risk of bleeding. Also, VTE may come back in a fifth of patients who are treated with warfarin.

Research has shown that a medicine known as low molecular weight heparin (LMWH) is better than warfarin at treating VTE in cancer patients and decreases the chance of VTE coming back by half. LMWH is given as an injection once a day. Studies have shown that giving the drug as an injection is acceptable to patients, as some patients prefer this to the regular blood tests they need to have for warfarin monitoring. LMWH is also simpler to use since it does not cause problems for patients taking other medicines which is a common problem for patients taking warfarin.

Cancer patients get VTE because the cancer can make the blood sticky and this makes it more likely to clot. It is recommended that patients take LMWH for six months only. However, if someone still has a cancer after six months of treatment with LMWH, there is still a strong chance that the VTE could come back because the cancer causing the blood clots has not gone away. This means that these patients might benefit from taking LMWH for longer than six months. We do not know though whether this would improve the patients' quality of life, help prevent death, or be cost-effective to the NHS.

To help decide if continuing with LMWH would benefit patients, we need to compare the effects of continuing with LMWH for an extra six months with the effects of not continuing LMWH in a clinical trial. Because this has not been done before, the first thing we need to do is see if it would be possible to carry out a full clinical trial with these patients. In other words, will we be able to recruit enough patients, will LMWH be a good treatment for them and will it be a reasonable cost?

To help answer these questions, we propose what is called a feasibility trial. This feasibility trial will compare patients who continue to take LMWH for a further six months with patients who do not continue to take LMWH. Patients with cancer, and who have been taking LMWH for five months for VTE, will be recruited from oncology and haematology outpatients departments and from GP practices.

Patients who are approached to take part in the study will be asked if they would be willing to continue with LMWH for a further six months as part of a research study. If they say yes, then they will be chosen at random to either receive the LMWH for a further six months (intervention group), or to stop LMWH at six months, which is usual care (control group). We will follow up patients for six months from recruitment and ask them to complete questionnaires at three monthly intervals. These questionnaires will ask about their symptoms and quality of life.

We will interview patients who do not wish to consent to the study to explore their reasons why. We will also interview patients who do consent to the study, but who later withdraw from the study to explore their experiences and reasons for withdrawal. We will also explore the views of clinicians towards continuation of LMWH and how they feel about the trial. Focus groups will be held with two groups of clinicians from each care setting. By collecting this information, we will be able to explore whether continuing with LMWH is something that is acceptable to patients and their health care professionals and if there are any side effects with continuing LMWH.

The research team is made up of experienced researchers from all health care settings (GPs, hospital doctors and nurses and health care professionals working in charity organisations). They are supported by approved clinical trials units, which are experienced in running large studies in all areas. The team members also have links to many national and international professional, policy and patient groups, which will be essential to help report the findings of this study.

Anticoagulation Length in Cancer Associated Thrombosis

A Feasibility Study to Inform the Design of a Randomised Controlled Trial to Identify the Most Clinically and Cost Effective Length of Anticoagulation With Low Molecular Weight Heparin In the Treatment of Cancer Associated Thrombosis

Toxicities, including bleeding events and VTEs, will be assessed during the 6 month trial treatment period.

Attitudes of clinicians and patients to extended treatment with LMWH will be assessed through clinician focus groups and qualitative interviews with patients and carers.

National Institute for Health Research, United Kingdom

Wales Cancer Trials Unit

Cardiff University

Senior Trial Manager

Micronutrients

Coagulants

Anti-Infective Agents

Vitamins

Amino Acids

Rivaroxaban

Vitamin K

Trace Elements

Factor Xa Inhibitors

Antithrombins

Antithrombin III

Protease Inhibitors

Serine Proteinase Inhibitors

HIV Protease Inhibitors

Enzyme Inhibitors

Antifibrinolytic Agents

Hemostatics

Menadione

Menaquinone

Naphthoquinone

Phylloquinone

Serine

Cancer patients who received anticoagulation treatment.

Retrospective cohort analysis using Swedish registries including the Cancer Registry, National Patient Registry, Prescribed Drug Registry, and Cause of Death Registry.

Rivaroxaban (Xarelto, BAY59-7939)

Low molecular weight heparin (LMWH)

vitamin K antagonist (VKA)

other NOACs

This is an observational study in which patient data from the past on venous thromboembolism (VTE) in patients with cancer is studied.

VTE is a condition in which a patient has problems due to the formation of blood clots in the veins. Blood clots can reduce the flow of blood to vital organs such as the heart and lungs, which can lead to them becoming damaged. VTE can also be "recurrent". This means that the blood clots have returned after treatment. People who have cancer have an increased risk of developing VTE.

Three main types of anticoagulation treatments ("blood thinners") have been available for patients with cancer who also have VTE

* Low molecular weight heparins (LMWHs)
* Vitamin K antagonists (VKAs)
* Non-vitamin K antagonist oral anticoagulants (NOACs) The treatment rivaroxaban belongs to the NOACs.

Compared to other treatments available to patients who have cancer and VTE, NOACs may cause fewer medical problems and can be easier for patients to take correctly.

In this study, the researchers will collect data about:

* the type of VTE treatments given and for how long the treatments are taken
* the risk of blood clots returning in the veins after treatment, any events of major bleeding, and the number of deaths in patients with cancer who do not have a high risk of bleeding

The researchers will compare this information in the patients

* who received rivaroxaban to the patients who received LMWHs
* who received NOACs to the patients who received LMWHs.

There will be no required visits with a study doctor or required tests in this study. The researchers will look at the health information from adult patients in Sweden who were diagnosed with cancer between 2013 and 2019 and also have VTE. The researchers will collect this information from Swedish health registers including the Cancer Registry, National Patient Registry, Prescribed Drug Registry, and Cause of Death Registry.

A Study to Gather Information About Rivaroxaban in Patients in Sweden With Cancer Who Also Have Thrombosis (OSCAR-SE)

Observational Studies in Cancer Associated Thrombosis for Rivaroxaban in SwEden (OSCAR-SE)

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Janssen Research & Development, LLC

Bayer

Warfarin

Edoxaban

Apixaban

Dabigatran

PENTA

Fondaparinux

Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator.

Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator.

If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized).

Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC).

If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized).

Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin.

Deborah Schrag, MD MPH

Jean Connors, MD

The overarching objective of the study is to determine the effectiveness of LMWH/ warfarin vs. DOAC anticoagulation for preventing recurrent VTE in cancer patients. The intervention strategy is Direct Oral AntiCoagulants (DOAC) therapy with edoxaban, apixaban, rivaroxaban, or dabigatran. The comparator is low molecular weight heparin (LMWH) alone or with warfarin. The information gained will empower cancer patients and physicians to make more informed choices about anticoagulation strategies to manage VTE.

Venous blood clots affect nearly a million Americans each year. Venous clots in the legs are called deep venous thrombosis (DVT) and are dangerous because they travel to the lungs where they cause blockages known as pulmonary emboli (PE). DVT and PE are called venous thromboemboli (VTE). Cancer is a risk factor with nearly 200,000 VTEs in cancer patients each year. The purpose of VTE treatment is to prevent the initial clot from spreading and to prevent new clots from forming. This is accomplished by thinning the blood, or anticoagulation. Without anticoagulation, VTEs recur and are often fatal.

Recently, the FDA has approved 4 new Direct Oral AntiCoagulants (DOACs) for preventing VTE recurrence. Few cancer patients were included in the efficacy trials, and practice guidelines fall silent on whether switching to DOAC therapy is advisable. To fill this knowledge gap, the Alliance Foundation Trials LLC, a research network of academic and community practices across the US, is conducting a pragmatic randomized effectiveness trial.

The overarching objective of the study is to determine the effectiveness of LMWH/ warfarin vs. DOAC anticoagulation for preventing recurrent VTE in cancer patients. The investigators will conduct a trial of 811 cancer patients followed for 6 months. The intervention strategy is DOAC therapy with edoxaban, apixaban, rivaroxaban, or dabigatran. The comparator is LMWH alone or with warfarin. Within each arm, patients can choose the agent they prefer based on side effects, drug interactions, and practical issues such as co-pays. The trial compares these two strategies in terms of treatment: 1) benefits based on VTE recurrence; 2) harms based on bleeding rates; 3) burdens based on patients' reports of their experiences; and 4) mortality rates.

The investigators hypothesize that the benefits, harms and burdens of DOAC treatment will be non-inferior to, or better than, usual care with LMWH/ warfarin among cancer patients. The information gained will empower cancer patients and physicians to make more informed choices about anticoagulation strategies to manage VTE.

Direct Oral Anticoagulants (DOACs) Versus LMWH +/- Warfarin for VTE in Cancer

Direct Oral Anticoagulants (DOACs) Versus LMWH +/- Warfarin for VTE in Cancer: A Randomized Effectiveness Trial (CANVAS Trial)

Individual-level de-identified datasets will be made available to investigators working under an institution with a Federal Wide Assurance (FWA) who formally submit a request to the study chairs at the Dana-Farber Cancer Institute. Prior to the release of datasets, DFCI will ensure certain requirements, e.g., IRB approval and data use agreement, are in place. These datasets will be available within 6 months of publication of the manuscript and following a formal request by an investigator to and approval from DFCI.

To compare the effectiveness of anticoagulation with a DOAC (intervention) with LMWH/warfarin (comparator) for preventing VTE recurrence in patients with cancer based on cumulative VTE recurrence reported by patients or clinicians at 6 months. Only VTEs that were nonfatal were considered because of the challenges of attributing cause of death in cancer patients to tumor progression vs. VTE.

To compare the harms of DOAC vs. LMWH/warfarin therapy for cancer patients with VTE based on the cumulative rate of major bleeding at 6 months. d. Major bleeding was defined as Grade \>=3 on the Common Terminology Criteria for Adverse Events from the National Cancer Institute (NCI CTCAE) criteria version 5.0 (i.e., severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living).

Change in physical health at 3 months. Health-related quality of life was measured using the 12-Item Short Form Health Survey (SF-12) sub-scales for physical and mental health (score range, 0-100; higher scores indicate better physical and mental health functioning). Survey content included minor verbiage changes for clarity. The presented scores in this results section indicate the change (difference) in mean scores between the baseline and 3-month follow-up assessment.

To compare the burden of anticoagulation therapy with DOAC vs. with LMWH/warfarin for cancer patients with VTE at 3 months. The burden scale has12 items and patients are asked to rate their experiences on a 5-point scale of intensity (1=not at all, 2=a little, 3=moderately, 4=quite a bit, 5=extremely). The ACTS burden tool is then scored using the totals from each question with a total score from 12 to 60 possible. Higher scores signify greater satisfaction (lower burden).

To compare the impact of DOAC vs. LMWH/warfarin therapy on mortality in cancer patients with VTE based on survival at 6 months. Mortality was reported by participants' surrogates (via study-specific questionnaire) or clinicians (via study-specific case report form)

Change in physical health at 6 months. Health-related quality of life was measured using the 12-Item Short Form Health Survey (SF-12) sub-scales for physical and mental health (score range, 0-100; higher scores indicate better physical and mental health functioning). Survey content included minor verbiage changes for clarity. The presented scores in this results section indicate the change (difference) in mean scores between the baseline and 6-month follow-up assessment.

To compare the burden of anticoagulation therapy with DOAC vs. with LMWH/warfarin for cancer patients with VTE at 6 months. The burden scale has12 items and patients are asked to rate their experiences on a 5-point scale of intensity (1=not at all, 2=a little, 3=moderately, 4=quite a bit, 5=extremely). The ACTS burden tool is then scored using the totals from each question with a total score from 12 to 60 possible. Higher scores signify greater satisfaction (lower burden).

To compare the benefit of anticoagulation therapy with DOAC vs. with LMWH/warfarin for cancer patients with VTE at 3 months. The benefits scale has 3 items and patients are asked to rate their experiences on a 5-point scale of intensity (1=not at all, 2=a little, 3=moderately, 4=quite a bit, 5=extremely). The ACTS benefits tool is then scored using the totals from each question with a total score from 3 to 15 possible. Higher scores signify greater satisfaction (greater benefits).

To compare the benefit of anticoagulation therapy with DOAC vs. with LMWH/warfarin for cancer patients with VTE at 6 months. The benefits scale has 3 items and patients are asked to rate their experiences on a 5-point scale of intensity (1=not at all, 2=a little, 3=moderately, 4=quite a bit, 5=extremely). The ACTS benefits tool is then scored using the totals from each question with a total score from 3 to 15 possible. Higher scores signify greater satisfaction (greater benefits).

Change in mental health at 3 months from baseline. Health-related quality of life was measured using the 12-Item Short Form Health Survey (SF-12) sub-scales for physical and mental health (score range, 0-100; higher scores indicate better physical and mental health functioning). Survey content included minor verbiage changes for clarity. The scores indicate change in score from baseline.

Change in mental health at 6 months from baseline. Health-related quality of life was measured using the 12-Item Short Form Health Survey (SF-12) sub-scales for physical and mental health (score range, 0-100; higher scores indicate better physical and mental health functioning). Survey content included minor verbiage changes for clarity. The scores indicate change in score from baseline.

Patient-Centered Outcomes Research Institute

Alliance Foundation Trials, LLC.

AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.

Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator.

Rivaroxaban: Anticoagulation therapy.

Apixaban: Anticoagulation therapy.

Edoxaban: Anticoagulation therapy.

Dabigatran: Anticoagulation therapy.

Randomized Arm 1 (DOACs)

Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator.

Warfarin: Anticoagulation therapy.

Dalteparin: Anticoagulation therapy.

Enoxaparin: Anticoagulation therapy.

Fondaparinux: Anticoagulation therapy.

Randomized Arm 2 (LMWH)

If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized).

Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC).

Rivaroxaban: Anticoagulation therapy.

Apixaban: Anticoagulation therapy.

Edoxaban: Anticoagulation therapy.

Dabigatran: Anticoagulation therapy.

Preference Cohort 1 (DOACs)

If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized).

Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin.

Warfarin: Anticoagulation therapy.

Dalteparin: Anticoagulation therapy.

Enoxaparin: Anticoagulation therapy.

Fondaparinux: Anticoagulation therapy.

Preference Cohort 2 (LMWH)

Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator.

Dalteparin: Anticoagulation therapy.

Enoxaparin: Anticoagulation therapy.

Fondaparinux: Anticoagulation therapy.

If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized).

Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin.

Dalteparin: Anticoagulation therapy.

Enoxaparin: Anticoagulation therapy.

Fondaparinux: Anticoagulation therapy.

Total

Age, Categorical

Age, median (q1, q3)

Age, Customized

Female

Male

Sex/Gender, Customized

Ethnicity (NIH/OMB)

Race (NIH/OMB)

This study has several limitations. First, participants and physicians were not blinded to treatment assignment. Second, because participants were randomized within 30 days of a new VTE diagnosis, some were treated with different therapy before randomization. Third, in patients with advanced-stage cancer, it was not possible to distinguish VTE from cancer as the cause of death. Fourth, the included population limits generalizability. Fifth, detailed medication diaries were not obtained.

Dr. Jean Connors

Primary analyses were performed on the participants who began protocol-directed therapy, the "as treated" population.

Cumulative Non-Fatal VTE Recurrence at 6 Months (%)

Cumulative Rates of Major Bleeding

Participants completing the 3-month survey assessment

Health Related Quality of Life Reported by Participants Via the Optum SF-12v2 Health Survey Questionnaire

Burden of Anticoagulation Therapy Reported by Participants Via the Anti-Clot Treatment Scale (ACTS) Questionnaire

Mortality Reported by Participants' Surrogates (Via Study-specific Questionnaire) or Clinicians (Via Study-specific Case Report Form)

Participants completing the 6-month survey assessment

Benefit of Anticoagulation Therapy Reported by Participants Via the Anti-Clot Treatment Scale (ACTS) Questionnaire

Participants completing the 6-moth survey assessment

Health Related Quality of Life (Mental Health) Reported by Participants Via the Optum SF-12v2 Health Survey Questionnaire at 3-months

Health Related Quality of Life (Mental Health) Reported by Participants Via the Optum SF-12v2 Health Survey Questionnaire at 6-months

Enrolled & Received Selected Treatment

6-Month Clinical Outcomes(Chart Review)

3-Month Patient-Reported Outcomes Survey

6-Month Patient-Reported Outcomes Survey

Recurrence

Cancer-associated thrombosis (CAT) patients treated with Rivaroxaban or any DOAC (Direct Oral Anticoagulants) or LMWH (Low molecular weight heparin).

Retrospective cohort analysis using US Optum De-Identified EHR data.

Retrospective cohort analysis using US Optum De-Identified EHR data. LMWH (dalteparin, enoxaparin, tinzaparin)

Retrospective cohort analysis using US Optum De-Identified EHR data. DOAC (apixaban, dabigatran, edoxaban, rivaroxaban).

Direct Oral Anticoagulants (DOAC)

Patients with active cancer are \~5-fold more likely to develop a venous thromboembolism (VTE) than those without. When VTE occurs, cancer patients carry an up to a 3-fold higher rate of thrombosis recurrence and \~twice the risk of bleeding during anticoagulation. Therefore, it is critical to utilize anticoagulants that optimize efficacy while minimizing bleeding risk when treating cancer-associated thrombosis (CAT).

Guidelines list direct-acting oral anticoagulants (DOACs) as an alternative to low molecular-weight heparin (LMWH) for treatment of CAT. The strength-of-recommendation for DOACs is based on data from multiple randomized controlled trials (RCTs) comparing them to LMWHs to treat CAT, with results suggesting DOACs may reduce thrombosis risk but with potentially more frequent bleeding (particularly in those with certain gastrointestinal and genitourinary cancers).

Observational studies evaluating DOACs for CAT treatment have been published, but these studies have been either single-arm, evaluated cancer subtypes not recommended for DOAC treatment, were of limited sample size and/or employed heterogeneous definitions of active cancer. We seek to evaluate the effectiveness and safety of rivaroxaban versus LMWH for CAT treatment in active cancer patients using a large de-identified electronic health record database.

Retrospective cohort analysis using US Optum® De-Identified EHR data. We will use Optum EHR (electronic health records) data from November January 1, 2012 through latest available data (currently September 2020).

Observational Studies in Cancer Associated Thrombosis for Rivaroxaban - United States Cohort

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Cunningham algorithm for identification of bleeding-associated hospitalizations

including:

* Intracranial hemorrhage (ICH)
* Critical organ bleeding (e.g., intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, or pericardial bleeding or intramuscular with compartment syndrome)
* Extracranial bleeding-related hospitalizations

per the Cunningham algorithm for identification of bleeding-associated hospitalizations

Incidence rates of recurrent VTE in DOAC and LMWH patients experiencing CAT regardless of the bleeding risk associated with cancer type.

Incidence rates of any clinically-relevant bleeding-related in DOAC and LMWH patients experiencing CAT regardless of the bleeding risk associated with cancer type.

Incidence rates of all cause-mortality in DOAC and LMWH patients experiencing CAT regardless of the bleeding risk associated with cancer type.

Neoplasms

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Antineoplastic Agents

Hematinics

Carboplatin

Osimertinib

Pemetrexed

Mitogens

Lazertinib

Amivantamab-vmjw

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Protein Kinase Inhibitors

Antineoplastic Agents, Immunological

Arginine

Leucine

Folinic Acid

Folate

Vitamin B9

Participants with treatment-naive locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) exon 19 deletion (exon19del) or exon 21 leucine 858 to arginine substitution (exon 21 L858R) mutation, will receive amivantamab SC-CF injection, 1600 milligrams (mg) or 2240 mg if body weight is greater than or equal to (\>=) 80 kilograms (kg), on Cycle 1 Days 1, 8, 15, and 22 and on Days 1 and 15 of each subsequent 28-day cycle, starting with Cycle 2, along with lazertinib 240 mg orally once daily.

Participants with treatment-naive locally advanced or metastatic NSCLC harboring an EGFR exon20ins mutation will receive Amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is \>=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is \>=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle, starting with Cycle 2 along with pemetrexed 500 milligrams per meter square (mg/m\^2) as intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle and IV infusion carboplatin area under the concentration-time curve 5 milligrams per milliliters (mg/mL) per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles.

Participants with locally advanced or metastatic NSCLC harboring an EGFR exon19del or exon 21 L858R mutation who have experienced disease progression on or after treatment with a third-generation EGFR TKI (osimertinib), will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is \>=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is \>=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m\^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression. Lazertinib 240 mg orally once daily starting Cycle 5 Day 1 when carboplatin is complete or sooner if carboplatin discontinued earlier than Cycle 4.

Participants with locally advanced or metastatic NSCLC harboring an EGFR exon19del or exon 21 L858R mutation who have experienced disease progression on or after treatment with a third-generation EGFR TKI (osimertinib), will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is \>=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is \>=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m\^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression.

Participants who were previously on amivantamab IV once every 2 weeks (Q2W) regimen as part of standard of care, for at least 8 weeks, either as monotherapy or combination with lazertinib, will receive amivantamab SC-CF injection 1600 mg and 2240 mg if body weight is greater than or equal to 80 kg.

Participants with treatment-naïve locally advanced or metastatic NSCLC harboring an EGFR Exon19del or Exon 21 L858R mutation will receive amivantamab SC-CF induction with 1,600 mg (or 2,240 mg if BW \>=80 kg) on Cycle 1 Days 1, 8, 15, and 22, starting with Cycle 2 on Day 1 of each next 28-day cycle, amivantamab SC-CF (160 mg/mL co-formulated with rHuPH20) by manual injection at 3,520 mg (or 4,640 mg if BW \>=80 kg); along with lazertinib 240 mg by mouth once daily from Cycle 1 Day 1.

Participants with treatment-naive locally advanced or metastatic NSCLC harboring an EGFR Exon19del or Exon 21 L858R mutation treated will receive will receive amivantamab SC-CF injection, 1600 milligrams (mg) and 2240 mg if body weight is greater than or equal to (\>=) 80 kilograms (kg), on Cycle 1 Days 1, 8, 15, and 22 and on Days 1 and 15 of each subsequent 28-day cycle, starting with Cycle 2, along with lazertinib 240 mg orally once daily from Cycle 1 Day 1. Participants will additionally take prophylactic anticoagulation with a direct oral anticoagulant (DOAC) or a low molecular weight heparin (LMWH) for the first four months of study treatment (from Day 1 through Day 120) with the combination of amivantamab and lazertinib.

Participants with locally advanced or metastatic NSCLC harboring an EGFR exon19del or exon 21 L858R mutation who have experienced disease progression on or after the combination of amivantamab and lazertinib will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is \>=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is \>=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m\^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression.

Amivantamab will be administered subcutaneously by manual injection.

Amivantamab

Lazertinib will be administered as an oral tablet.

Carboplatin will be administrated by IV infusion.

Pemetrexed will be administered by IV infusion.

Direct Oral Anticoagulant (DOAC)

LMWH will be administered subcutaneously.

Study Contact

Janssen Research & Development, LLC Clinical Trial

The purpose of this study is to assess the anti-tumor activity and safety of amivantamab which will be administered as a co-formulation with recombinant human hyaluronidase PH20 (rHuPH20) (subcutaneous co-formulation \[SC-CF\]) in combination treatment (all cohorts except Cohort 4) and to characterize the safety of amivantamab SC-CF (Cohort 4).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Anticoagulation Length in Cancer Associated Thrombosis	NCT01817257	Cancer Thrombosis Venous Thromboe... Deep Vein Throm... Pulmonary Embol...	Low Molecular W...	16 Years -	Cardiff University
A Study to Gather Information About Rivaroxaban in Patients in Sweden With Cancer Who Also Have Thrombosis (OSCAR-SE)	NCT05150938	Treatment of Ve...	Rivaroxaban (Xa... Low molecular w... vitamin K antag... other NOACs	18 Years -	Bayer
A Study to Gather Information About Rivaroxaban in Patients in Sweden With Cancer Who Also Have Thrombosis (OSCAR-SE)	NCT05150938	Treatment of Ve...	Rivaroxaban (Xa... Low molecular w... vitamin K antag... other NOACs	18 Years -	Bayer
Direct Oral Anticoagulants (DOACs) Versus LMWH +/- Warfarin for VTE in Cancer	NCT02744092	Cancer Venous Thromboe... Deep Vein Throm... Pulmonary Embol... Blood Clot	Rivaroxaban Apixaban Edoxaban Dabigatran Warfarin Dalteparin Enoxaparin Fondaparinux	18 Years -	Alliance Foundation Trials, LLC.
Observational Studies in Cancer Associated Thrombosis for Rivaroxaban - United States Cohort	NCT04979780	Treatment of Ve... Prophylaxis of ...	Rivaroxaban (Xa... Low molecular w... Direct Oral Ant...	18 Years -	Bayer
Observational Studies in Cancer Associated Thrombosis for Rivaroxaban - United States Cohort	NCT04979780	Treatment of Ve... Prophylaxis of ...	Rivaroxaban (Xa... Low molecular w... Direct Oral Ant...	18 Years -	Bayer
A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer	NCT05498428	Carcinoma, Non-...	Amivantamab Lazertinib Carboplatin Pemetrexed Direct Oral Ant... Low Molecular W...	18 Years -	Janssen Research & Development, LLC
A Study to Gather Information About Rivaroxaban in Patients in Sweden With Cancer Who Also Have Thrombosis (OSCAR-SE)	NCT05150938	Treatment of Ve...	Rivaroxaban (Xa... Low molecular w... vitamin K antag... other NOACs	18 Years -	Bayer
Direct Oral Anticoagulants (DOACs) Versus LMWH +/- Warfarin for VTE in Cancer	NCT02744092	Cancer Venous Thromboe... Deep Vein Throm... Pulmonary Embol... Blood Clot	Rivaroxaban Apixaban Edoxaban Dabigatran Warfarin Dalteparin Enoxaparin Fondaparinux	18 Years -	Alliance Foundation Trials, LLC.

Spots Global Cancer Trial Database for low molecular weight heparin (lmwh)