Perioperative Testosterone Replacement Therapy in Sarcopenic Male Colorectal Cancer Patients

Colorectal Cancer Clinical Trial

— TERESA  

Official title:

Use of Perioperative Testosterone Replacement Therapy (TRT) in Sarcopenic Male Colorectal Cancer Patients - A Single Arm Open Label Feasibility Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05367284
• Other study ID #: RD21/025
• Status: Recruiting
• Start date: January 15, 2022
• Est. completion date: March 2023

Study information

• Verified date: October 2021
• Source: London North West Healthcare NHS Trust
• Contact: Ioanna Drami, MSc, MRCS
• Phone: +4420 8864 3232
• Email: i.drami20[@]imperial.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

With increasing age and the additional impact from the bowel cancer and the chemotherapy and/ or radiotherapy it has been described that testosterone (a male hormone produced naturally in the body) levels are reduced. Testosterone has an impact on numerous body functions including the muscle mass and quality. Previous studies have identified that muscle mass is reduced as a result of ageing but also because of the deleterious effect of cancer and chemotherapy and/or radiotherapy. There is growing evidence from published studies that patients with better muscle mass and quality, do better after surgery. Mr Jenkins and his team are therefore looking at ways, the investigators can try and prevent or reduce this muscle loss and therefore improve patient outcomes. The aim of this study is to assess whether using testosterone replacement therapy in the form of a topically applied gel daily for a total of 12 weeks, is feasible and acceptable by the patients who are diagnosed with colorectal cancer and are waiting to undergo surgery. The investigators will also collect information related to the testosterone replacement therapy such as questionnaires on the quality of life, fatigue and muscle mass, and blood biomarker changes in the blood.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 2023
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 45 Years and older

Eligibility

Inclusion Criteria:

• Male = 45 years old
• Colorectal cancer - histology confirmed
• Identified as sarcopenic on latest computerised tomography (CT) scan prior to intervention (part of initial investigations - using Martin et al (2013) criteria - 43cm2/m2 for Body Mass Index (BMI) <25, 53cm2/m2 for BMI>25)
• Documented low or normal testosterone at time of recruitment (<12 nano moles/ Litre (nmol/L)
• Eligible for operative intervention
• Capacity to consent
• Able to mobilise & able to complete the 6 Minute Walk Test (MWT)
• Post completion of chemotherapy/ chemoradiotherapy treatment (if the patient has neoadjuvant treatment)
• Booked straight for surgery with an interim of 4-8 weeks.
• Participation in another concurrent trial/ study is accepted, following discussion between the two trial /study teams

Exclusion Criteria:

• Not sarcopenic on computerised tomography (CT)
• Not eligible for surgery
• History of Deep Vein Thrombosis (DVT)/ Pulmonary Embolism (PE)/ prostate cancer/ breast cancer
• Prostate nodule identified during digital rectal examination (DRE) or magnetic resonance imaging (MRI) pelvis
• Multiple distant metastasis which are non-operable
• Prostate specific antigen (PSA) > 3 nanogram/ mililitre (ng/ml)
• Haematocrit (HCT) >52%
• Severe lower urinary tract symptoms
• Class III/ IV heart failure
• Myocardial Infarct or stroke within the last 6 months
• Dementia / No capacity to consent
• Patient on medications with anti-androgen effect eg spironolactone
• Patients with untreated severe obstructive sleep apnoea
• Morbid obesity as defined by Body Mass Index (BMI) >40
• Uncontrolled hypertension
• Patients on long term steroids during the trial period
• Patient on other anabolic agents
• Not already on treatment for primary hypogonadism
• Patients with bone metastasis

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Hypogonadism
• Hypogonadism, Male
• Perioperative Care
• Sarcopenia

Intervention

Drug:
• Testosterone
Testogel 16.2 miligrams/ gram (mg/g) gel

Locations

Country	Name	City	State
United Kingdom	London North West University Healthcare NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
London North West Healthcare NHS Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (27)

Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, Bunnell TJ, Tricker R, Shirazi A, Casaburi R. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med. 1996 Jul 4;335(1):1-7. — View Citation

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Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jan 1;48(1):16-31. doi: 10.1093/ageing/afy169. Erratum in: Age Ageing. 2019 Jul 1;48(4):601. — View Citation

Del Fabbro E, Garcia JM, Dev R, Hui D, Williams J, Engineer D, Palmer JL, Schover L, Bruera E. Testosterone replacement for fatigue in hypogonadal ambulatory males with advanced cancer: a preliminary double-blind placebo-controlled trial. Support Care Cancer. 2013 Sep;21(9):2599-607. doi: 10.1007/s00520-013-1832-5. Epub 2013 May 8. — View Citation

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Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremner WJ, McKinlay JB. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab. 2002 Feb;87(2):589-98. — View Citation

Gillessen S, Templeton A, Marra G, Kuo YF, Valtorta E, Shahinian VB. Risk of colorectal cancer in men on long-term androgen deprivation therapy for prostate cancer. J Natl Cancer Inst. 2010 Dec 1;102(23):1760-70. doi: 10.1093/jnci/djq419. Epub 2010 Nov 10. — View Citation

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Herbst KL, Bhasin S. Testosterone action on skeletal muscle. Curr Opin Clin Nutr Metab Care. 2004 May;7(3):271-7. Review. — View Citation

Jang MK, Park C, Hong S, Li H, Rhee E, Doorenbos AZ. Skeletal Muscle Mass Change During Chemotherapy: A Systematic Review and Meta-analysis. Anticancer Res. 2020 May;40(5):2409-2418. doi: 10.21873/anticanres.14210. Review. — View Citation

Lee CM, Kang J. Prognostic impact of myosteatosis in patients with colorectal cancer: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle. 2020 Oct;11(5):1270-1282. doi: 10.1002/jcsm.12575. Epub 2020 Jun 1. — View Citation

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Pring ET, Malietzis G, Kennedy RH, Athanasiou T, Jenkins JT. Cancer cachexia and myopenia - Update on management strategies and the direction of future research for optimizing body composition in cancer - A narrative review. Cancer Treat Rev. 2018 Nov;70:245-254. doi: 10.1016/j.ctrv.2018.10.002. Epub 2018 Oct 6. Review. — View Citation

Sah BK, Chen MM, Peng YB, Feng XJ, Yan M, Liu BY, Fan QS, Zhu ZG. Does testosterone prevent early postoperative complications after gastrointestinal surgery? World J Gastroenterol. 2009 Nov 28;15(44):5604-9. — View Citation

Santa Mina D, van Rooijen SJ, Minnella EM, Alibhai SMH, Brahmbhatt P, Dalton SO, Gillis C, Grocott MPW, Howell D, Randall IM, Sabiston CM, Silver JK, Slooter G, West M, Jack S, Carli F. Multiphasic Prehabilitation Across the Cancer Continuum: A Narrative Review and Conceptual Framework. Front Oncol. 2021 Jan 11;10:598425. doi: 10.3389/fonc.2020.598425. eCollection 2020. Review. — View Citation

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Trejo-Avila M, Bozada-Gutiérrez K, Valenzuela-Salazar C, Herrera-Esquivel J, Moreno-Portillo M. Sarcopenia predicts worse postoperative outcomes and decreased survival rates in patients with colorectal cancer: a systematic review and meta-analysis. Int J Colorectal Dis. 2021 Jun;36(6):1077-1096. doi: 10.1007/s00384-021-03839-4. Epub 2021 Jan 22. Review. — View Citation

Walsh JS, Marshall H, Smith IL, Greenfield DM, Swain J, Best E, Ashton J, Brown JM, Huddart R, Coleman RE, Snowden JA, Ross RJ. Testosterone replacement in young male cancer survivors: A 6-month double-blind randomised placebo-controlled trial. PLoS Med. 2019 Nov 12;16(11):e1002960. doi: 10.1371/journal.pmed.1002960. eCollection 2019 Nov. — View Citation

Wischmeyer PE, Suman OE, Kozar R, Wolf SE, Molinger J, Pastva AM. Role of anabolic testosterone agents and structured exercise to promote recovery in ICU survivors. Curr Opin Crit Care. 2020 Oct;26(5):508-515. doi: 10.1097/MCC.0000000000000757. Review. — View Citation

Wright TJ, Dillon EL, Durham WJ, Chamberlain A, Randolph KM, Danesi C, Horstman AM, Gilkison CR, Willis M, Richardson G, Hatch SS, Jupiter DC, McCammon S, Urban RJ, Sheffield-Moore M. A randomized trial of adjunct testosterone for cancer-related muscle loss in men and women. J Cachexia Sarcopenia Muscle. 2018 Jun;9(3):482-496. doi: 10.1002/jcsm.12295. Epub 2018 Apr 14. — View Citation

Wu B, Lorezanza D, Badash I, Berger M, Lane C, Sum JC, Hatch GF 3rd, Schroeder ET. Perioperative Testosterone Supplementation Increases Lean Mass in Healthy Men Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial. Orthop J Sports Med. 2017 Aug 9;5(8):2325967117722794. doi: 10.1177/2325967117722794. eCollection 2017 Aug. — View Citation

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* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of days required for a patient to be recruited on the study and how many patients are recruited	number of days required for patients to be recruited and number of patients recruited by the closure of the study	1 year
Primary	Number of patients who will complete the 12 week treatment	retention of the patients for a the total of 12 weeks by the time of recruitment, will be measured in days on study	12 weeks
Primary	Treatment acceptability questionnaire	questionnaire on the difficulty experience (Likert scale) for the use of the gel for 12 weeks, if they developed any side effects as described on the CTCAE version 5.0	12 weeks