Testosterone treatment for the management of fatigue in ambulatory patients with advanced cancer: A pilot feasibility double-blind placebo-controlled study

INTERVENTION: The Intervention is a topical testosterone cream (Androforte 50mg/ml or Androfeme 10mg/ml) vs a placebo cream. All participants will be randomised at a 1:1 ratio for the application of topical testosterone vs placebo cream daily for 4 weeks. Male participants will be allocated Androforte 50mg/ml or placebo and female participants will be allocated Androfeme 10mg/ml or placebo. Participants will be instructed to apply one (1) mL of the cream daily, at the same time each morning within a two hour window. One (1) ml of cream is applied to the scrotum in men; and to the upper thigh, buttocks or upper torso over intact skin in women. After applying the cream, hands should be thoroughly washed. No showering, swimming or physical skin‐to‐skin contact with application site unless covered with clothing for 4 hours post application. The total duration of treatment is 4 weeks. Participants will be required to keep the cream tubing to enable compliance to be checked, and all tubes will be returned to the dispensing pharmacy. To further assess compliance participants will also maintain a diary of application, and will be asked at each study contact. At the end of the 4 weeks treatment, each participant will be offered a 4 week open label extension of testosterone treatment. CONDITION: Cancer ‐ Other cancer types Cancer;Fatigue; ; Cancer ; Fatigue PRIMARY OUTCOME: The primary objective is to determine feasibility of the study to conduct a further definitive Phase III randomized control trial (RCT). This is determined by the ability to recruit 26 participants within 12 months as well as Treatment Completion (TC) [Defined as the percentage of randomised participants who complete the four‐week treatment window, this must be at least 80% of randomized participants. 60% or less would be considered unacceptable.; ; Completion will be measured from the participant diary of treatment compliance. Complete diaries from 26 participants will be required in order to meet the primary objective. The number of participants who complete the four‐week treatment window will be assessed at 12 months post‐commencement of recruitment.] INCLUSION CRITERIA: Adult men and women with advanced cancer, solid organ or haematopoietic malignancy 18 years or older The Palliative Care Outcome Collaboration (PCOC) Symptom Assessment Score (SAS) of 3 or greater for fatigue Australia ‐ modified Karnofsky Performance Status Palliative Score of 40 or above Able to give informed consent as determined by the treating clinician Able to complete study procedures and comply with study procedures No indication of primary hypogonadism on the completion of the screening reproductive function questionnaire SECONDARY OUTCOME: Change in fatigue [Measured by the Functional Assessment of Chronic Illness Therapy (FACIT) ; ‐Fatigue subscale ; Measured at Baseline, week 2, week 4, week 8 post baseline] Change in health‐related Quality of Life (QOL)[Measured by the Functional Assessment of Cancer Therapy – General (FACT‐G) scale Baseline, week 2, week 4 and week 8 post baseline] Change in Hemoglobin[Measured by venous blood sample, analysed in laboratory Baseline, week 4 and week 8 post baseline] Change in libido[Measured by the 15‐ Item International Inde Xof Erectile Function [IIEF]) in men; ; or the Short Item 6 Female Sexual Function Inde XFSFI for females Baseline, week 4, and week 8 post baseline] Change in mood[Measured by the Hospital and Anxiety Depression Scale (HADS) Baseline and week 4 post baseline] Change in serum testosterone levels[Measured by venous blood sampling and laboratory analysis Baseline, week 4 and week 8 post baseline] Difference between groups of toxicity data[Measured by systematic recording of Adverse Events using the National Cancer Institute, Common Terminology Criteria for Adverse Events Baseline and week 2, week 4, week 6, week 8 post baseline and weeks 1 and 2 of follow‐up post treatment completion] Differences between groups of participant assessment of blinding[Participant completion of blinding assessment questions designed for this study in order to assess the feasibility and burden of a larger trial Week 4 post baseline or early termination or withdrawal] Treatment completion after an 8‐week period[Completed the 4 weeks of intervention and 4 weeks of open label extension using the participant completed diary. 8 Weeks post baseline]