Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Recurrence

Breast Neoplasms

Prostatic Neoplasms

Disease Attributes

Esophageal Cancer

Antipyretics

Anti-Inflammatory Agents

Antirheumatic Agents

Fibrinolytic Agents

Analgesics

Platelet Aggregation Inhibitors

All Drugs and Chemicals

Aspirin

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Aspirin 100mg

Aspirin 300mg

Placebo 100mg

Placebo 300mg

Alex Robbins

Olawale Tijani

Ruth Langley

Add-Aspirin aims to assess whether regular aspirin use after standard curative therapy can prevent recurrence and improve survival in individuals with non-metastatic common tumours. The question will be assessed in four different tumour types (breast, colorectal, gastro-oesophageal and prostate) by means of parallel cohorts within an overarching trial protocol.

Eligible participants will be randomly assigned (double-blind) to either aspirin 100mg, aspirin 300mg or a matched placebo, to be taken daily for at least 5 years. Disease recurrence and survival will be assessed, along with adherence, toxicity, and other potential effects of aspirin (eg. cardiovascular).

There is a large body of evidence indicating that aspirin has anti-cancer effects. Meta-analyses of cardiovascular trials of aspirin have shown short-term effects on cancer mortality and a decrease in risk of metastases, suggesting a role for aspirin in the treatment as well as prevention of cancer. Additionally, large observational studies of individuals taking aspirin after cancer treatment have shown improved disease-specific and overall mortality for specific tumour types.

In the treatment setting, the risks of side effects associated with aspirin are expected to be outweighed by potential benefits. However, this has not yet been assessed in a randomised trial.

As a low cost, generic and widely available drug, which is generally safe, if aspirin is shown to be effective, it could have a huge impact on cancer outcomes globally.

A phase III, multi-centre, double-blind, placebo-controlled randomised trial which aims to assess whether regular aspirin use after standard therapy prevents recurrence and prolongs survival in participants with non-metastatic common solid tumours.

The trial has four parallel tumour site-specific cohorts (breast, colorectal, gastro-oesophageal and prostate cancer). An overarching protocol ensures each cohort is as comparable as possible to allow a combined analysis of overall survival as a co-primary outcome measure in addition to individual tumour site-specific analyses of disease recurrence and survival.

Participants who have undergone potentially curative treatment (surgery or other radical treatment), including any standard neo-adjuvant or adjuvant therapy for breast, colorectal, gastro-oesophageal or prostate cancer or have participated in any pre-approved trials and satisfy the eligibility criteria.

Participants will be randomly assigned to 100mg aspirin, 300mg aspirin or matched placebo. All tablets will be enteric-coated to be taken daily for at least five years. Prior to randomisation, all potential participants will take open-label 100mg aspirin daily for a run-in period of approximately 8 weeks to assess tolerability and adherence.

The trial incorporates a feasibility phase during which recruitment feasibility, treatment adherence, safety and use of the run-in period will be assessed.

Add-Aspirin: A Trial Assessing the Effects of Aspirin on Disease Recurrence and Survival After Primary Therapy in Common Non Metastatic Solid Tumours

A Phase III, Double-blind, Placebo-controlled, Randomised Trial Assessing the Effects of Aspirin on Disease Recurrence and Survival After Primary Therapy in Common Non Metastatic Solid Tumours

Overall survival in the gastro-oesophageal cancer cohort

Patient-reported compliance (via diary card) will be assessed during the run-in period

University College, London

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

Amino Acids

Osimertinib

Mitogens

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Osimertinib and Aspirin starting at a dose of 80 mg and 100mg once a day, orally with meals. Aspirin treatment will be initiated one week before beginning TKI therapy, if possible, but TKI therapy will not be delayed for Aspirin loading. Drug: Osimertinib and Aspirin will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity.

Osimertinib starting at a dose of 80 mg once a day, orally with meals. Drug: Osimertinib will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity.

Aspirin, also known as acetylsalicylic acid (ASA), is a very safe medication used to treat pain, fever, or inflammation.

Osimertinib, also known as azd9291, is a 3rd-generation EGFR-TKI used to treat NSCLC patients with resistance to 1st generation EGFR-TKI due to T790M mutation. It has been approved in clinical applications by the FDA in 2015.

Osimertinib 80 MG

yong he, doctor

The third generation epidermal growth factor receptor-tyrosine Kinase Inhibitor（EGFR-TKI） osimertinib has obvious curative effect for EGFR sensitive mutation and T790M mutation(PMID 27959700), but acquired drug resistance will occur. Previous studies show that apoptosis escape can lead to EGFR-TKI resistance.Osimertinib resistant cells show abnormal activation of PI3K/AKT/BIM activation(PMID 28765329). The classical drug aspirin can effectively decrease AKT phosphorylation and activate of BIM(PMID 28881293).So Investigators speculate that aspirin may decrease the PI3K/AKT/BIM signaling pathways, then promote osimertinib resistant cells apoptosis. The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations.

Reversible small-molecule EGF receptor tyrosine kinase inhibitors (EGFR-TKI) have shown dramatic therapeutic efficacy in non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations, and have been recommended as the standard first-line therapy in these patients. However, despite excellent initial clinical responses, nearly all patients eventually develop drug resistance after a median period of about 10 months(PMID 26497205). Osimertinib is a 3rd-generation EGFR-TKI used to treat NSCLC patients with resistance to 1st generation EGFR-TKI due to T790M mutation. But Osimertinib also face the problem of acquired drug-resistance(PMID 27959700). Thus, innovative treatment strategies are urgently needed to overcome therapeutic resistance to Osimertinib to improve the survival of patients with NSCLC.

Molecular mechanisms underlying acquired Osimertinib resistance are still not fully understood. Previous study showed that one principal mechanism accounting for majority of acquired resistance to Osimertinib in lung cancer is mediated by an exon 20 C797S mutation etc(PMID 29596911). More molecular mechanisms are still to be found. Apoptosis is a process of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, chromosomal DNA fragmentation, and global mRNA decay. Apoptosis has been found to be related to drug resistance to 1st generation EGFR-TKI(PMID 29731879). The investigators previous found apoptosis is also related to Osimertinib resistance(PMID 28765329). Therefore, promoting apoptosis may be an effective way to improve the response to Osimertinib treatment.

Investigators' group has focused on lung cancer targeted therapy for several years. Previously, investigators have reported that metformin in combination with 1st generation EGFR-TKI could enhance the effect of TKI (PMID 24644001). Therefore, investigators further asked whether the drug combination approach could overcome osimertinib resistance. Aspirin is a widely used and well-tolerated drug for Kawasaki disease, pericarditis, and rheumatic and has arisen keen interest as a potential anticancer agent ever since the report of the clinical evidence that the cancer risk and mortality are reduced in Colon cancer. Aspirin exerts remarkable antitumor properties in tumor cells and mouse models. It strongly inhibited the growth of lung cancer cells, and its combination with TKI agents, including Sorafenib (PMID: 28857200), significantly suppressed RAS-mutant cancers growth and prolonged remission in a xenograft model. Interestingly, Aspirin exposure significantly promoted the apoptosis suggesting that aspirin may overcome Osimertinib resistance by promoting the apoptosis.

Here, investigators'group observed that in clinic, several patients who took osimertinib and aspirin together have shown excellent effect.Investigators therefore conduct this clinical trial to observe whether the combination of Aspirin and Osimertinib could enhance efficacy of Osimertinib in lung cancer patients with EGFR mutation.

Combination of Osimertinib and Aspirin to Treat EGFR Mutation NSCLC Patients

Prospective Observational Trial to Evaluate the Efficacy of the Combination of Osimertinib and Aspirin in Patients With Epidermal Growth Factor Receptor(EGFR)-Mutation

To evaluate the response to therapy and progression-free survival rate of the combination of Osimertinib and Aspirin in advanced lung cancer patients who has EGFR-mutation.

To evaluate the overall survival of the combination of Osimertinib and Aspirin in advanced lung cancer patients who has EGFR-mutation.

To evaluate the response to therapy and Objective Response Rate of the combination of Osimertinib and Aspirin in patients who has EGFR-mutation.

To evaluate the response to therapy and Time to progression of the combination of Osimertinib and Aspirin in patients who has EGFR-mutation.

Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

Department of Respiratory Disease, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

Heart and Blood Diseases

Thrombosis

Venous Thrombosis

Embolism

Embolism and Thrombosis

Vascular Diseases

Anticoagulants

Anti-Infective Agents

Heparin

Rivaroxaban

Calcium heparin

Factor Xa Inhibitors

Antithrombins

Antithrombin III

Protease Inhibitors

Serine Proteinase Inhibitors

HIV Protease Inhibitors

Serine

Rivaroxaban 10mg

low molecule heparin

Jian Huang, Doctor

Gui Nv Hu, Doctor

Wen J Chen, Doctor

Pei F Fu, Doctor

Zhi Y Feng

Zhen Y Wang, Doctor

Jing P Long, Doctor

Xiao H Xie, Doctor

Gui P Chen, Doctor

Xiao C Wang, Doctor

Shi L Tu, Doctor

Yun H Wei, Doctor

Shu Z Fang, Doctor

Juan Y Zhu, Doctor

Shu G Li, Doctor

Shu Z Chen, Doctor

Qing H Shen, Doctor

Yong Shi, Doctor

Yi J Mei, Doctor

Jia M Lei, Doctor

Lv J Cen, Doctor

Yan Zhang, Doctor

Ying J Wu, Doctor

Zhan W Li, Doctor

Jian Zhang, Doctor

Ou C Wang, Doctor

Min Zheng, Doctor

Jing Xu, Doctor

The main objective of this study is to compare the efficacy and safety of aspirin, low molecule heparin and rivaroxaban for preventing catheter-related thrombosis in middle-to-high-risk ambulatory patients with cancer and implantable venous access ports.

Study Type: Interventional, randomized, parallel Assignment and no masking

Study Arms \& Intervention: Drug 1: Aspirin, 100mg/day orally; Drug 2: rivaroxaban, 10mg/day orally; Drug 3: low molecule heparin, 4000IU(0.4ml)/day subcutaneous injection; Reference: mechanical prophylaxis.

Follow-up Period: 6 months. The trial visits occurred at time before each chemotherapy cycle. The following details should be included at each visit: Khorana score, height and weight, blood routine examination, coagulation function, stool-routine and occult blood test, renal and liver function, ultrasonography of both legs and neck.

Primary Outcome: The primary efficacy end point was the occurrence of thrombus in the vein at the puncture site or nearby. The primary was the occurrence of a major bleeding event as defined by the International Society on Thrombosis and Haemostasis (ISTH).

Secondary Outcome: The secondary efficacy end point was occurrence of occurrence of other thrombosis or embolism events like deep vein thrombosis or pulmonary embolism. The secondary safety endpoint was the occurrence of any clinically relevant non-major bleeding, minor bleeding and adverse events.

Population: patients with cancer and implantable venous access ports

Eligibility Criteria:

1. Age 18-75 years;
2. Patients with malignant tumors who received implantable drug delivery devices as intravenous access for systematic chemotherapy;
3. Eastern Cooperative Oncology Group (ECOG) class 0-1;
4. Expected to receive chemotherapy within 1 week of enrollment;
5. Expected survival of more than 6 months;
6. Ambulatory patients or outpatient chemotherapy patients whose intravenous chemotherapy less than 24 hours per hospital stay;
7. Khorana score 1-3 point.

Exclusion Criteria:

1. Patients with a history of allergies to low molecular weight heparin, rivaroxaban, aspirin or other non-steroidal anti-inflammatory drugs, especially those with asthma, neurovascular edema or shock;
2. Patients with bleeding risks: thrombocytopenia (platelet count \< 50\*109/L), clinically significant active bleeding, active gastric ulcer disease, severe arterial hypertension, history of previous stroke;
3. moderate to severe liver and kidney dysfunction;
4. pregnant or lactating women;
5. patients who are administered systemically with pyrrole-antimycotic agents (eg ketoconazole, itraconazole, voriconazole and posaconazole) or HIV protease inhibitors (eg ritonavir);
6. Patients taking methotrexate;
7. Patients with systemic use of non-steroidal anti-inflammatory drugs;
8. Patients who have had anticoagulant drugs for any other reason.

Prophylactic Anticoagulation for Catheter-related Thrombosis

The Efficacy and Safety of Prophylactic Anticoagulation for Catheter-related Thrombosis in Patients With Cancer and Implantable Venous Access Ports: a Prospective Multi-center Randomized Controlled Trial.

detect the occurrence of catheter-related thrombosis with ultrasound, venography if necessary

define occurrence of major-bleeding event with ISTH standard

detect deep vein thrombosis with ultrasound for the lower extremity, , ultrasound for the upper extremity, pulmonary arteriography or venography if necessary

define occurrence of non-major-bleeding or minor-bleeding event with ISTH standard, evaluate the relevant adverse drug reaction with NCI CTCAE 5.0

Second Affiliated Hospital, School of Medicine, Zhejiang University

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Add-Aspirin: A Trial Assessing the Effects of Aspirin on Disease Recurrence and Survival After Primary Therapy in Common Non Metastatic Solid Tumours	NCT02804815	Cancer Breast Cancer Prostate Cancer Colorectal Canc... Gastro-oesophag...	Aspirin 100mg Aspirin 300mg Placebo 100mg Placebo 300mg	16 Years -	University College, London
Combination of Osimertinib and Aspirin to Treat EGFR Mutation NSCLC Patients	NCT04184921	Lung Cancer Non...	Aspirin 100mg Osimertinib 80 ...	18 Years - 80 Years	Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Add-Aspirin: A Trial Assessing the Effects of Aspirin on Disease Recurrence and Survival After Primary Therapy in Common Non Metastatic Solid Tumours	NCT02804815	Cancer Breast Cancer Prostate Cancer Colorectal Canc... Gastro-oesophag...	Aspirin 100mg Aspirin 300mg Placebo 100mg Placebo 300mg	16 Years -	University College, London
Prophylactic Anticoagulation for Catheter-related Thrombosis	NCT04256525	Venous Thrombos... Prophylactic An... Patients With T...	Rivaroxaban 10m... Aspirin 100mg low molecule he...	18 Years - 75 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University

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