None listed
Conditions
Brief summary
Cancer stem cells (CSCs) account for a small proportion of the cells within a cancerous tumour, but play a crucial role in the features of cancer that can make it difficult to cure, including cancer spread and recurrence. CSCs are resistant to traditional cancer treatments such as chemotherapy and radiotherapy. Preliminary studies suggest that the antibiotic doxycycline may inhibit CSCs, and could therefore be used along-side traditional cancer treatments to improve cancer outcomes. Colorectal (bowel) cancer is a major health problem in New Zealand, with 3000 new diagnoses and 1200 deaths per year. Rectal cancer refers to a cancer which affects the distal end of the bowel. A standard treatment for rectal cancer in which the tumour is advanced but there is no distant spread is a five day course of radiotherapy (also known as short-course radiotherapy or SCRT) followed by surgery to remove the cancer within approximately one to two weeks. We aim to recruit 20 people with rectal cancer who are having SCRT to take two 100mg doxycycline tablets each day during radiotherapy and continue it up until the day before their cancer surgery. We will also recruit 20 control participants, who have recently undergone radiotherapy and surgery for rectal cancer but did not take doxycycline. We will assess the effects of radiotherapy and doxycycline on the CSCs in each participant’s cancer and make comparisons between the patients who did and did not take doxycycline. We will also look at the difference between the CSCs in each patients surgical sample, compared to their original biopsy sample from which the cancer diagnosis was made. It is hoped that if the study shows a positive outcome, then it may ultimately lead to a larger, longer-term study on the effect of doxycycline on cancer outcomes such as risk of recurrence in future patients receiving radiotherapy for rectal cancer.
Interventions
Doxycycline is a broad-spectrum antibiotic, which prevents the binding of amino-acyltRNA to the messenger RNA-30S ribosomal subunit, preventing polyribosome formation. It is approved in New Zealand for the treatment of chronic prostatitis, sinusitis, syphilis, pelvic inflammatory disease, malaria, recurrent aphthous ulceration, and acne vulgaris. Doxycycline primarily exerts it's antimicrobial action by bacteriostasis. It also has antinflammatory effects.
Doxycycline will be administered as tw
Doxycycline is a broad-spectrum antibiotic, which prevents the binding of amino-acyltRNA to the messenger RNA-30S ribosomal subunit, preventing polyribosome formation. It is approved in New Zealand for the treatment of chronic prostatitis, sinusitis, syphilis, pelvic inflammatory disease, malaria, recurrent aphthous ulceration, and acne vulgaris. Doxycycline primarily exerts it's antimicrobial action by bacteriostasis. It also has antinflammatory effects. Doxycycline will be administered as two 100mg tablets orally each morning, starting two days prior to the first dose of short-course radiotherapy (SCRT), until one day prior to surgery for rectal cancer. Surgery will be performed within three weeks of starting radiotherapy treatment. The duration of doxycycline will be between 12 and 23 days, and will be determined by each participant's individual treatment schedule. Adherence will be assessed through a combination of a patient diary, and count of the number of tablets remaining in the drug container on the patients admission for rectal cancer surgery.
Sponsors
Dr Natalie Briggs
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Pathologically-confirmed rectal adenocarcinoma. 2. Magnetic resonance imaging (MRI) stage T3-4, and/or N1-2, or full thickness low T2 lesions where R0 resectability is in doubt. 3. ECOG performance status of 0–2. 4. Adequate liver function on blood tests taken within four weeks of commencing doxycycline (e.g. ALT/AST <3 x ULN, bilirubin <1.5 x ULN). 5. Surgery planned to occur within 3 weeks of starting SCRT. 6. Willing and able to comply with all trial requirements, including treatment and timing and/or nature of required assessments. 7. Signed, written informed consent.
Exclusion criteria
1. Received chemotherapy for their rectal cancer prior to SCRT; 2. Allergy to doxycycline. 3. Currently taking medications with which doxycycline is known to have clinically-significant drug-drug interactions including systemic retinoids, oral antacids, oral iron or calcium, carbamazepine, phenytoin, enzalutamide, lithium, ergotamine, diuretics, oral contraceptive pill, quinapril, rifampicin, warfarin, methotrexate, st johns wort, ciclosporin. 4. Myasthenia gravis; 5. Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety. 6. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol. 7. Prior high dose radiotherapy to the pelvis. 8. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to starting treatment. Men must have been surgically sterilised or use a barrier method of contraception.
Outcome results
None listed