Addition of Aspirin to Standard of Care in Oral Cancer

NCT ID: NCT05865548

Last Updated: 2024-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-17
• Study Completion Date: 2024-08-10

Brief Summary

Despite accumulating evidence of the benefit of aspirin in cancer, its effect on improving cancer survival is still debated since the mechanism by which it impacts cancer survival is not completely understood and the published data are discordant. There have been 4 randomized controlled trials (RCT) showing mixed results from no effect to improved survival. Several retrospective and observational studies have reported a survival advantage of adding aspirin to the treatment for various cancers. A meta-analysis of 118 studies, 63 of them specifically reporting on cancer mortality and the rest on all-cause mortality, found a 21% reduction in cancer deaths and about 20% reduction in all-cause mortality (pooled hazard ratio (HR): 0.79; 95% confidence intervals: 0.73, 0.84).

However, the evidence is still lacking and there is need to do more RCT

Detailed Description

Aspirin (ASA), an NSAID, is a well-known antipyretic and analgesic agent and is used to prevent recurrent transient ischemic attacks or strokes. In addition to its classical anti- inflammatory function, clinical and epidemiological studies indicate that aspirin can be used as a preventive or therapeutic agent in multiple cancers, including oral cancers

While the exact mechanism through which NSAIDs contribute to chemo prevention is not completely understood, Aspirin inhibits the enzyme Cox; Cox-1 and Cox-2 are well characterized. Cox converts a arachidonic acid to prostaglandin H2, which in turn produces biologically active prostaglandins that influence path physiological processes in a range of tissues including angiogenesis, apoptosis, cell proliferation and migration, inflammatory response and thrombosis. Inhibition of prostaglandin synthesis is considered the pre dominant mechanism by which NSAIDs act as anti-inflammatory agents, but it is unclear whether the anti-cancer properties of these agents can be solely attributed to Cox inhibition.

Recently, Cox-2 over expression has been identified in a number of different malignancies and it has been hypothesized that Cox-2 prostaglandins promote tumor genesis by inhibiting apoptosis, modulating the immune system and regulating tumor associated angiogenesis.

A detailed search of literature and bio informatics analysis of the data obtained showed that the effect of Aspirin on survival and prevention of recurrence and secondary cancer could be due to its effect on following 11 genes PTGS2, PIK3CA, PARP1, PARP2, VEGFA, KDR, PTGES2, NFKB1, P53, FLT1, VEGFR. These genes not only interact and control each other but also control cell cycle regulation through other genes as shown below. These could be due to co expression, physical interactions, shared domains or predicted interactions in absence of data.

Based on the gene-gene and protein-protein interactions they can be clustered into three with PTGES2, PTGS2 and p53 being in first cluster (figure 2 below), the NGS data obtained from the previous patients also showed the p53 to be the primary driver gene (unpublished data, submitted) in nearly 50% of the subjects. It has also been shown that patients with p53 mutations

have poor survival and increased recurrence rates compared to those without p53 mutations. This coupled with literature showing improved survival and low recurrence in patients receiving Aspirin suggest the need for a RCT as this has never been done before.

Conditions

Oral Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Interventional arm

Aspirin 150mg PO daily along with standard of care

Group Type: EXPERIMENTAL

Aspirin 150 mg

Intervention Type: DRUG

Aspirin 150 mg PO daily

Standard of care

Standard of care as per the stage of disease and guidelines i.e. Surgery, Surgery with radiation or palliative chemotherapy as per investigators choice

Group Type: ACTIVE_COMPARATOR

Standard of care

Intervention Type: PROCEDURE

Surgery with or without radiation, palliative chemo as per investigators choice

Interventions

Aspirin 150 mg

Aspirin 150 mg PO daily

Intervention Type: DRUG

Standard of care

Surgery with or without radiation, palliative chemo as per investigators choice

Intervention Type: PROCEDURE

Other Intervention Names

Radiation, chemotherapy

Eligibility Criteria

Inclusion Criteria

• All Histologically proven cases of primary oral cancers.
• Stage T1 to T4, N0 to N3, M0 to M1.
• Age above 18.
• Karnofsky' performance status more than 70, ECOG 0 to 2
• Hb >8.0 gm/dL
• Total count >4000 cu mm
• Platelet count >100000 Serum creatinine <1.0mg
• Liver enzymes up to 1.5 times normal
• Bilirubin <1.0mg

Exclusion Criteria

• Patients with acid peptic disease
• Pregnant and lactating women.
• Patients not willing to participate.
• Patients with known allergy to NSAID
• Patients with Asthma, rhinitis and nasal polyps
• Presence of viral fever
• Use of any other blood thinner like warfarin, heparin or low molecular weight heparin
• bleeding/blood-clotting disorders (such as hemophilia, vitamin K deficiency, low platelet count)
• pyruvate kinase or G6PD deficiency
• Patients receiving mifepristone, acetazolamide, corticosteroids, dichlorphenamide, methotrexate, valproic acid, herbal medications (such as ginkgo biloba)
• Patients with recent history of anti-viral vaccines

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Banaras Hindu University

OTHER

Sponsor Role: lead

Responsible Party

Manoj Pandey

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Manoj Pandey

Role: PRINCIPAL_INVESTIGATOR

Professor

Locations

Banaras Hindu University

Varanasi, Uttar Pradesh, India

Countries

India

Other Identifiers

HNC02

Identifier Type: -

Identifier Source: org_study_id