None listed
Conditions
Brief summary
Cancer cachexia is a syndrome of progressive weight loss, anorexia, and persistent reduction of body cell mass in response to a malignant tumour. In cancer cachexia there is the extensive loss of adipose tissue and equal amounts of skeletal muscle mass. The incidence of cachexia is type of tumour and site dependent. Small-Cell and NSCLC patients experience a high incidence of cachexia, 57% and 61% respectively. It is associated with a deterioration of functional status and quality of life and is also associated with poor survival. Muscle wasting is the main cause of impaired function, leading to respiratory complications and fatigue.There is a need to support cachectic lung cancer patients after their chemotherapeutic regimens, especially with the added knowledge that chemotherapy treatment will add to their overall weight loss and cachectic state. The optimal treatment for cancer cachexia is the complete removal of the tumour; unfortunately with many advanced solid tumours this is unachievable, especially in the case of NSCLC patients. The next best options are to increase nutritional intake to counteract the weight loss, address the anorexia, inflammation, and the metabolic alterations i.e. loss of body fat and the skeletal muscle wasting. This study aims to identify a novel treatment
Interventions
Arm A ‘International best supportive care’ is defined as 2g /day of EPA oral and 300mg / day of COX-2 inhibitor (Celebrex) oral for 20 weeks. Arm B ‘Treatment group’ is defined as 2g / day of EPA oral, 300mg / day of COX-2 inhibitor (Celebrex) oral, Progressive Resistance Training (2 episodes per week, involving 5-10 minute warmup, 10-15 minutes resistance training followed by 5 minute cool-down, approximately 30 minutes increasing in time to 1 hour per session, commencing on a one-to-one basis
Arm A ‘International best supportive care’ is defined as 2g /day of EPA oral and 300mg / day of COX-2 inhibitor (Celebrex) oral for 20 weeks. Arm B ‘Treatment group’ is defined as 2g / day of EPA oral, 300mg / day of COX-2 inhibitor (Celebrex) oral, Progressive Resistance Training (2 episodes per week, involving 5-10 minute warmup, 10-15 minutes resistance training followed by 5 minute cool-down, approximately 30 minutes increasing in time to 1 hour per session, commencing on a one-to-one basis and moving onto a group sessions if required by participant, under supervision of a trained exercise therapist) plus 20g essential amino acids high in leucine over 3 days commencing 1 hour post exercise, oral, for 20 weeks.
Sponsors
Pfizer
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients who have diagnosed NSCLC and have received at least a first-line anti-cancer treatment e.g. surgery, chemotherapy, radiotherapy or a targeted therapy (i.e. gefitinib, erlotinib and crizotinib) and fulfil the following cachexia definition Q1 Has lost 5% of oedema-free body weight in the previous 12 months or less Q2 Mild less than or equal to 5%, Moderate greater than 10%, Severe greater than 15% Q3 If no documented weight loss, Is BMI of less than 20.0 kg/m2 Q4 At least 3 out of the following 5 1. Decreased muscle strength 2. Experiencing fatigue either measured by a VO2 max score or patient confirmed reduced physical activity 3. Anorexia 4. Low fat-free mass index (low muscle mass) 5. Abnormal biochemistry, CRP greater than 5.0mg/L IL-6 greater than 4.0pg/ml anaemia Hb less than 12.0g/dL hypoalbuminemia less than 3.2g/dL Inclusion criteria: 1. Patients greater than or equal to 18 years old 2. Histologically confirmed non-small cell carcinoma of the lung. (Histological or cytological specimens must be collected via surgical biopsy, brushing, washing or core needle aspiration of a defined lesion. Sputum cytology is not acceptable) 3. Patients should be aware of the diagnosis of cancer 4. Patients able to give written informed consent obtained according to local guidelines 5. Fulfils above ‘cachectic definition’ 6. Karnofsky Scoreequal to 60 or ECOG Performance Status 0,1, 2 or 3 7. Recently completed first-line platinum-based chemotherapy 8. Lab values within the range, as defined below, within 2 weeks of randomisation: 1. Absolute neutrophils count (ANC) greater than 2.0 x 109/L 2. Platelets greater than or equal to 100 x 109/L 3. Haemoglobin greater than or equal to 100 g/dL 4. Serum creatinine less than or equal to 1.5 x ULN (= 120 micro mol/L) 5. Serum bilirubin less than or equal to 1.5 x ULN (= 25 micro mol/L) 6. Aspartate transaminase (AST) and alanine transaminase (ALT)less than or equal to 2.5 x ULN (less than or equal to 5 x ULN if liver metastases) 7. Electrolyte values (potassium, calcium, magnesium) within greater than 1 x LLN and less than 1 x ULN 8. Females of child-bearing potential must have negative serum pregnancy test (confirmation of negative urine pregnancy test within 72 hours prior to initial dosing) 9. Life expectancy greater or equal to 20 weeks
Exclusion criteria
Exclusion criteria: 1. Patients who are, in the opinion of a doctor or nurse in the department, unlikely to be suitable to participate by virtue of mental incapacity, severe current psychological or psychiatric disorder 2. Patients with an estimated prognosis of less than one month 3. Concurrent use of other investigational agents and patients who have received investigational agents in the last 4 weeks prior to randomisation 4. Concurrent use of other appetite stimulants e.g. MPA or MA and 4mg OD dexamethasone or 30mg OD prednisolone 5. Patients with systolic BP > 160 mm HG and/or diastolic > 90 mm HG 6. Pleural effusion that causes a CTC grade 2 dyspnoea 7. Radiotherapy in the last 2 weeks prior to randomisation. Patients must have recovered from all radiotherapy-related toxicities 8. Patients with a history of another primary malignancy within last 5 years with the exception of non-melanoma skin cancer or cervical cancer in situ 9. Patients having CNS metastases (Patients having any clinical signs of CNS metastases must have a CT or MRI of the brain performed to rule out CNS metastases in order to be eligible for study participation. Patients who have had brain metastases surgically removed or irradiated with no residual disease confirmed by imaging are allowed) 10. Patients with recent haemoptysis associated with NSCLC (> 1 teaspoon in a single episode within 4 weeks) 11. Patients with an abnormal Baseline 12-lead ECG 12. Concurrent severe and/or uncontrolled medical disease (i.e. uncontrolled diabetes, chronic renal failure, chronic liver disease Patient unwilling or unable to comply with the study protocol
Outcome results
None listed