A Safety and Effectiveness Study of Pre-operative Artesunate in Stage II/III Colorectal Cancer

NCT ID: NCT02633098

Last Updated: 2022-10-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-04-26

Study Completion Date

2025-10-31

Brief Summary

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This study evaluates the safety and effectiveness of pre-operative artesunate given orally once a day for 14 days prior to surgery in patients with Stage II/III colorectal cancer.

Artesunate is an established antimalarial drug with an excellent safety profile, is well tolerated and affordable. A number of laboratory studies and one small pilot clinical study in patients with colorectal cancer have shown that artesunate can reduce the proliferation and growth of cancer cells.

Two hundred patients diagnosed with Stage II/III operable colorectal cancer will be randomly allocated to receive oral artesunate 200mg daily or a matching placebo for 14 days prior to surgery. Patients will be followed up closely for 5 years to see if giving artesunate preoperatively reduces the risk of cancer recurring after surgery.

Detailed Description

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Artesunate is an established antimalarial drug belonging to the artemisinin class of drugs, has an excellent safety profile, is well tolerated and affordable. In last two decades, artemisinins have shown potent and broad anticancer properties in a range of cell lines and animal models, supporting the hypothesis that artemisinins have the potential to be an effective anti-cancer therapy. Multiple potential mechanisms of action include anti-proliferative effects through cell-cycle disruption, reactive oxygen species (ROS) -induced DNA damage, induction of apoptosis, anti-angiogenesis, immunomodulation and induced radiosensitivity.

Despite a multi-modality treatment approach to colorectal cancer, 5 year overall survival does not currently exceed 60%. Neoadjuvant pre-operative therapy may be more effective at eradicating micrometastases compared to adjuvant therapy delivered following the delay and immunological stress of surgery. However current neoadjuvant chemotherapy regimens are often associated with significant side effects and may result in a delay in surgery whilst patients recover. A well tolerated, affordable, novel anticancer agent that could be given to patients whilst they wait for surgery, without causing a surgical delay due to treatment related toxicity, would have a significant clinical impact on patient care.

The NeoART trial is a phase II multicentre randomised, double blind, placebo controlled trial (RCT) for patients undergoing primary surgery for Stage II/III colorectal cancers. Patients are randomised (1:1 ratio) to receive either a two week course of neoadjuvant artesunate 200mg once daily or matching placebo. Both patients and health care professionals are blinded to treatment allocation arm to minimise outcome-reporting bias. The primary endpoint of the trial is recurrence free survival two years after surgery. Secondary endpoints include 2 and 5 year overall survival, treatment related toxicity, tolerability and patient quality of life. A translational sub-study looking at predictive and prognostic biomarkers is also planned.

Conditions

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Colorectal Cancer Bowel Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Artesunate

Artesunate 200mg oral tablets once daily for 14 days.

Group Type EXPERIMENTAL

Artesunate 200mg

Intervention Type DRUG

Artesunate 200mg PO OD for 14 days prior to colorectal resection surgery

Matching placebo

Matching placebo oral tablets once daily for 14 days.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matched placebo PO OD for 14 days prior to colorectal resection surgery

Interventions

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Artesunate 200mg

Artesunate 200mg PO OD for 14 days prior to colorectal resection surgery

Intervention Type DRUG

Placebo

Matched placebo PO OD for 14 days prior to colorectal resection surgery

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Aged 18 or over
2. Histologically proven single primary site colorectal adenocarcinoma or high grade dysplasia plus unequivocal radiological evidence of invasive cancer
3. Stage II/III colorectal cancer planned for surgical resection and no clinical indication for neoadjuvant preoperative chemotherapy/chemoradiation therapy
4. WHO performance status 0,1 or 2
5. Adequate full blood count: White Cell Count (WCC) \>3.0 x 10\^9 /l; Platelets \>100 x 10\^9/l; Haemoglobin (Hb) \>80g/L
6. Adequate renal function: Glomerular Filtration Rate \>30ml/min by Cockcroft-Gault formula
7. Adequate hepatobiliary function : Bilirubin \< 3 x Upper limit normal
8. Female participants of child bearing potential must have a negative pregnancy test \< 72 hours prior to initiating study intervention and agree to avoid pregnancy using adequate, medically approved contraceptive precautions for up to 6 weeks after the last dose of study treatment intervention
9. Male participants with a partner of childbearing potential must agree to use adequate, medically approved contraceptive precautions during and for up to 6 weeks after the last dose of the study treatment intervention
10. Patient able and willing to provide written, informed consent for the study.

Exclusion Criteria

1. Contraindication to the use of artesunate due to hypersensitivity
2. Pregnancy or lactation
3. Male or female participants unwilling to use an effective method of birth control (either hormonal in the form of contraceptive pill or barrier method of birth control accompanied by the use of a proprietary spermicidal foam/gel or film); or agreement of true abstinence from time to consent is signed until 6 weeks after the last dose of study treatment intervention (i.e. withdrawal, calendar, ovulation, symptothermal and post ovulation methods are not considered acceptable methods)
4. History of immunosuppression
5. History of hearing or balance problems
6. Weight \< 52kg or \> 110kg
7. Other planned intervention, apart from standard of care
8. Any other malignant disease diagnosis within the preceding 2 years with the exception of non-melanomatous skin cancer and carcinoma in situ
9. Lactose intolerance
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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St George's, University of London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Professor Sanjeev Krishna, BMBCh, DPhil, ScD

Role: PRINCIPAL_INVESTIGATOR

St George's University Hospitals NHS Foundation Trust

Locations

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Medway Maritime Hospital

Gillingham, Kent, United Kingdom

Site Status COMPLETED

Kent Oncology Centre, Maidstone Hospital

Maidstone, Kent, United Kingdom

Site Status COMPLETED

Barking, Havering and Redbridge University Hospitals NHS Trust

Barking, , United Kingdom

Site Status RECRUITING

Ashford & St Peters Hospital NHS Foundation Trust

Chertsey, , United Kingdom

Site Status RECRUITING

University Hospitals of Derby and Burton NHS Foundation Trust

Derby, , United Kingdom

Site Status RECRUITING

St George's University Hospitals NHS Fundation Trust

London, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Norfolk & Norwich University Hospitlas NHS FT

Norwich, , United Kingdom

Site Status RECRUITING

Shrewsbury and Telford Hospital NHS Trust

Shrewsbury, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Professor Sanjeev Krishna, FRCP, ScD, FMedSci

Role: CONTACT

++44(0)208 725 5836

Dr Yolanda Augustin, MBBS, MRCP, FRCR, MSc

Role: CONTACT

++44(0)2087255722

Facility Contacts

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Nirooshun Dr Rajendran

Role: primary

01708 435000 ext. 3615

Alison Ray

Role: backup

01708 435000 ext. 3615

Pasha Mr Nisar

Role: primary

01932 722318

Victoria Frost

Role: backup

01932 723534

Stelios Vakis

Role: primary

01283 566333

Helen Cox

Role: backup

01283 56633

Adam Stearns

Role: primary

01603 287372

Cheryl Websdale

Role: backup

01603 288894

Jon Mr Lacy-Colson

Role: primary

01743 261000 ext. 1460

Sally Potts

Role: backup

01743 261000 ext. 1692

Other Identifiers

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15.0154

Identifier Type: -

Identifier Source: org_study_id

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