Trial name or title

Anti‐inflammatory and nutritional support, with simple exercises in lung cancer patients with weight loss

Methods

After patients complete the screening procedures at the screening visit and the principal investigator has confirmed that all inclusion/exclusion criteria have been met, all eligible patients will be randomly assigned to a treatment arm. Enclosed treatment assignments will be serially numbered in opaque, sealed envelopes and opened sequentially after the participant's name and other details have been written on the appropriate envelope. Enclosed treatment assignments will be serially numbered in opaque, sealed envelopes and opened sequentially after the participant's name and other details have been written on the appropriate envelope. Simple randomisation by using a randomisation table created by computer software (i.e. computerised sequence generation)

Participants

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 5.0 mg/L, IL‐6 greater than 4.0 pg/ml anaemia, Hb less than 12.0 g/dL, hypoalbuminaemia less than 3.2 g/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 Score equal to 60 or ECOG Performance Status 0, 1, 2 or 3
7. Recently completed first‐line platinum‐based chemotherapy
8. Laboratory 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:
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 1 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 4 mg OD dexamethasone or 30 mg OD prednisolone
5. Patients with systolic BP > 160 mmHg and/or diastolic > 90 mmHg
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

Age minimum: 18 years

Age maximum: no limit

Gender: both males and females

Interventions

Arm A: 'International best supportive care' is defined as 2 g/day of EPA oral and 300 mg/day of COX‐2 inhibitor (Celebrex) oral for 20 weeks
Arm B: 'Treatment group' is defined as 2 g/day of EPA oral, 300 mg/day of COX‐2 inhibitor (Celebrex) oral; progressive resistance training (2 episodes per week, involving 5 to 10‐minute warm‐up, 10‐ to 15‐minute 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 group sessions if required by participant, under supervision of a trained exercise therapist) plus 20 g essential amino acids high in leucine over 3 days commencing 1 hour post exercise, oral, for 20 weeks

Outcomes

Primary outcome 1: acceptability of the treatment regimen will be assessed by asking patients to complete a questionnaire asking if they found the regimen acceptable and if they wish to continue with the treatment

Secondary outcome 1: lean body mass assessed by bioelectrical impedance analysis (Tanita BC‐418 Segmental Body Composition Analyzer, Tanita)
Secondary outcome 2: MRI thigh skeletal muscle values as assessed (treatment allocation is blinded) by University MRI department

Secondary outcome 3: QoL and fatigue assessed by the following questionnaires MFSI‐SF, FAACT, WHOQOL‐BREF

Secondary outcome 4: serum levels of pro‐inflammatory classic cachexia cytokines (IL‐1, IL‐6 and TNF‐alpha) measured by Bio‐Plex Pro assay, Bio‐Rad)

Secondary outcome5: hand grip strength assessed by hand grip dynamometry of the dominant hand, the average of 3 attempts with 1‐minute rest between attempts

Secondary outcome 6: leg strength assessed by a customised leg extension rig (chair) with a cell load of the right leg, the average of 3 attempts with a 1‐minute rest between attempts

Secondary safety outcome 1: serious adverse events (SAEs) and adverse events (AEs), e.g. cardiac changes on ECG. All symptoms assessed using the NCI CTC

Secondary safety outcome 2: Glasgow Prognotic Score (GPS)

Secondary safety outcome 3: Karnofsky Score (KS)

Secondary safety outcome 4: progression‐free survival (PFS) will be assessed from the date of consent until documented radiology proven (CT) progression

Secondary safety outcome 5: overall compliance will be assessed by returned study medication and the number of PRT sessions attended

Secondary safety outcome 6: RECIST data (if available)

Starting date

5 June 2012

Contact information

Bruce Arroll ‐ [email protected]

Notes

Trial ID ‐ ACTRN12611000870954

Trial name or title

A feasibility study of multimodal exercise/nutrition/anti‐inflammatory treatment for cachexia ‐ the Pre‐MENAC Study

Methods

This is a multicentre, open, randomised phase II study

The eligibility criteria are:

• advanced non‐small‐cell lung cancer (stage III‐IV) or pancreatic cancer not eligible for curative therapy

• due to commence chemo‐ or chemoradiotherapy

• Karnofsky Performance Score ≥ 70

• a life expectancy of ≥ 4 months and considered able to complete 2 months of the study

Participants

Men and women of 18 to 80 years old with cancer cachexia

Interventions

Nutritional supplements aimed at optimal energy balance and protein intake (2 cartons of ProSure per day), nutritional advice, home‐based self assisted exercise programme and anti‐inflammatory treatment (300 mg celecoxib) for 6 weeks. The aerobic exercise programme is performed as self administered daily walking sessions, aiming for a minimum of 2 sessions of 30 minutes on a weekly basis. Other aerobic activities could be used instead of walking. The resistance exercise programme should be performed 3 times weekly and last about 20 minutes. The programme is targeting major muscle groups in the upper body and legs with use of weights. The intensity of the exercise and performance of the exercises are adapted to the individual patient's disease burden and physical performance

Outcomes

Feasibility of recruitment and retention.

Starting date

16 August 2011

Contact information

Stein Kaasa, MD, PhD ‐ [email protected]

Ken Fearon, MD, PhD ‐ [email protected]

Notes

—

Trial name or title

Exercise and Nutrition for Head and Neck Cancer Patients (ENHANCE)

Methods

Inclusion criteria:

• Over 18 years of age

• Has received a diagnosis of nasopharyngeal, oropharyngeal or hypopharyngeal cancer

• Will receive radiation as part of treatment plan

• Able to walk without assistance

• Received clearance for exercise from treating oncologist

• Lives in Calgary, Alberta area

• Can speak and write English

• Is interested in participating in the study

Allocation: randomised

Intervention model: parallel assignment

Masking: single‐blind (outcomes assessor)

Primary purpose: supportive care

Participants

Cancer of head and neck

Interventions

• Behavioural: Lifestyle Intervention: participants in the Lifestyle Intervention will receive a 12‐week individualised exercise and dietary programme based on their exercise assessment and dual energy x‐ray absorptiometry (DXA) scan results, will attend twice weekly group exercise classes, and perform their individualised at‐home programme an additional 2 times per week. In addition, participants will be required to attend 6 education sessions during the 12‐week intervention

• Behavioural: Maintenance Intervention: patients randomised to receive the Maintenance Intervention following treatment will receive a Survivorship Care Plan outlining their physical activity, dietary and health behaviour progress throughout the programme, future goals, individualised maintenance strategies and optional drop‐in exercise sessions

Outcomes

Change from baseline in body composition (time frame: at baseline (diagnosis), and then at 3, 6, 9 and 12 months post diagnosis) (designated as safety issue: no)

DXA scan will be used to assess body composition

Quality of life (time frame: at baseline (diagnosis), and then at 3, 6, 9 and 12 months post diagnosis) (designated as safety issue: no)

Quality of life will be assessed using the Functional Assessment of Cancer Therapy ‐ Anaemia module (FACT‐AN), and the NCCN‐FACT Fact Head/Neck Symptom Index‐22 (FHNSI‐22)

Physical activity behaviour (time frame: at baseline (diagnosis), and then at 3, 6, 9 and 12 months post diagnosis) (designated as safety issue: no)

Physical activity will be assessed using Godin's (Godin 1985) leisure score index (LSI) of the GLTEQ (Godin Leisure Time Exercise Questionnaire)

Smoking history (time frame: at baseline (diagnosis), and then at 3, 6, 9 and 12 months post diagnosis) (designated as safety issue: no)

Smoking history will be assessed by a self report questionnaire which will classify patients as non‐smokers, former smokers and current smokers

Depression (time frame: at baseline (diagnosis), and then at 3, 6, 9 and 12 months post diagnosis) (designated as safety issue: no)

Depression will be assessed using the Center for Epidemiological Studies on Depression Scale (CES‐D)

Karnofsky Performance Score (KPS) (time frame: at baseline (diagnosis), and then at 3, 6, 9 and 12 months post diagnosis) (designated as safety issue: no)

The Karnofsky Performance Score (KSP) will be used to measure the participant's general ability to accomplish tasks of daily‐living and overall well‐being

Inflammatory markers (time frame: at baseline (diagnosis), and then at 3, 6, 9 and 12 months post diagnosis) (designated as safety issue: no)

Inflammatory factors will be evaluated as they are associated with cancer cachexia and muscle wasting and may be modified by exercise (Seruga 2008; Baldwin 2011). An overnight fasted blood draw will be collected at baseline, 3 months post diagnosis, 6 months post diagnosis, 9 months post diagnosis and 12 months post diagnosis. Serum inflammatory cytokine concentrations will be assessed in‐house (Dr. Raylene Reimer's laboratory) according to our established protocols. TNF, IL‐6, IL‐1, IL‐8 and C‐reactive protein will be quantified using Milliplex Human Cytokine kits (Millipore, Billerica, MA). Plate reading will be provided as a fee‐for service through Eve Technologies Inc. (Calgary, AB)

Cancer‐related symptom management (time frame: at baseline (diagnosis) and then 3, 6, 9, 12 months post diagnosis and every week before and after class during the 12‐week intervention) (designated as safety issue: no)

Participants will complete the ESAS bi‐weekly, before and after class. The ESAS is a valid and reliable assessment tool to evaluate the 9 more common symptoms experienced by cancer patients (Chang 2000)

Diet behaviour ‐ 3‐day food record (time frame: at baseline (diagnosis) and 4 and 8 weeks, 3, 6, 9, 12 months post diagnosis) (designated as safety issue: no)

The 3‐day diet record is said to be the most accurate for mean macronutrient content and appropriate for use in studies where participants may consume a wide variety of foods (American Dietetics Association/Dietitians Canada, 2000). Participants are instructed to record their daily consumption over a period of 3 days, 1 of which must be a weekend day. Written instructions and a sample entry are provided to increase accuracy of the daily record

Diet behaviour: PG‐SGA (time frame: at baseline (diagnosis), each week during radiation treatment (6.5 weeks in duration), and 3, 6, 9, 12 months post diagnosis) (Designated as safety issue: No)

The PG‐SGA assessment tool has been show to improve treatment outcomes, decrease side effects and improve weight management in cancer patients, and therefore will be used weekly to assess and identify malnutrition among patients (McMahon 2000; Doyle 2006)

Health‐related fitness measures ‐ resting heart rate (time frame: at baseline (diagnosis), and 3, 6, 9, 12 months post diagnosis.) (designated as safety issue: no)

Resting heart rate will be measured by palpating the radial artery and taking a 15‐second count as per the CPAFLA protocol (CPAFLA 2003)

Health‐related fitness outcome ‐ blood pressure (time frame: at baseline (diagnosis), and 3, 6, 9, 12 months post diagnosis.) (designated as safety issue: no)

A resting blood pressure (mmHg) will be measured in duplicate on the left arm using a sphygmomanometer and stethoscope using standardised procedures (CPAFLA 2003)

Health‐related fitness outcome ‐ 6‐minute walk test (time frame: at baseline (diagnosis), and 3, 6, 9, 12 months post diagnosis.) (designated as safety issue: no)

The 6‐minute walk test (6MWT) will be used to assess changes in functional aerobic capacity. Using the standardised protocol, participants will be asked to walk as far as they can around a 400 m track for 6 minutes. The point reached at 6 minutes will be marked and measured to the nearest 0.5 m. Rating of perceived exertion (Borg scale) will be completed immediately after completion of the functional aerobic capacity test

Health‐related fitness outcome ‐ grip strength (time frame: at baseline (diagnosis) and 3, 6, 9, and 12 months post diagnosis.) (designated as safety issue: no)

Muscular strength will be assessed using a combined grip strength of the right and left hands will also be assessed using a hand dynamometer. A sum will be determined in kilograms from the best score of 2 trials recorded for each hand according to the CPAFLA protocol

Health‐related fitness outcome ‐ lower body strength (time frame: at baseline (diagnosis), and 3, 6, 9, and 12 months post diagnosis) (designated as safety issue: no)

Lower body strength will be assessed using a 30‐second sit to stand test. The number of times participants can stand from a seated position in 30 seconds will be examined

Health‐related fitness outcome ‐ flexibility (time frame: at baseline (diagnosis) and 3, 6, 9, and 12 months post diagnosis) (designated as safety issue: no)

Flexibility will be assessed by a trunk forward flexion sit‐and‐reach test using a Wells‐Dillon flexometer. The test will follow a standard protocol, with 2 trials allowed and the highest score to the nearest 0.5 cm recorded

Health‐related fitness outcome ‐ balance (time frame: at baseline (diagnosis), and 3, 6, 9, and 12 months post diagnosis.) (designated as safety issue: no)

Balance will be assessed using a static balance test. The test requires the participant to balance on one foot and then the other as long as they can (length of time to a maximum of 45 seconds) while standing on a 2.54 by 2.54 by 30.5 cm base using a standardised protocol, reported by Fleishman

Starting date

June 2012

Contact information

Nicole Culos‐Reed ‐ [email protected]

Notes

Trial ID ‐ NCT01681654