Effect of Lenalidomide (Revlimid®) in Solid Tumour Patients With Inflammatory Cancer Cachexia Syndrome on Lean Body Mass and Muscle Strength: A Multicenter, Proof-of-concept Study of Fixed Dose or CRP-response-guided Dose of Lenalidomide in Relation to New Standard Basic Cachexia Management (Receiving Placebo).
1. Age: Patients must be older than 18 years of age.
2. Tumour situation: Patients with any type of advanced (defined as locally recurrent or
metastatic), incurable solid tumour.
3. Cachexia: Presence of CCS, defined as involuntary loss of weight of ≥2% in 2 months
or ≥5% in 6 months, which is ongoing in the last 4 weeks, and lack of fluid
4. Inflammation: CRP must be ≥ 30mg/l in the absence of any other more likely cause of
increased CRP like an infection or an autoimmune disorder.
5. No simple starvation: Patients must be able to eat, defined as no severe structural
barriers in the upper gastrointestinal tract and no bowel obstruction.
6. Life expectancy, physical performance: Patient must have an expected life expectancy
> 3 months according to palliative performance (Pap) score and a WHO performance
status (PS) ≤ 2.
7. No anti-cachexia or appetite-stimulating medications: Patients are not allowed to
have corticosteroids unless for maximum 2 days per week for chemotherapy, progestin
therapy, Cyclooxigenase-2 inhibitor (COX-2 inhibitor), and anabolic drugs 28 days
before start of trial medication until study conclusion. Prokinetic medication, NSAR,
paracetamol and novamin sulphate are allowed, if given in a fixed dose for two weeks
before visit 1, and expected to be given during the whole trial period.
8. Laboratory test results: Granulocyte count ≥ 1.5 x 109/L, platelet count ≥ 100 x
109/L, serum creatinine ≤ 2.0 mg/dL (177 μmol/L), creatinine clearance ClCr ≥
50ml/min, total bilirubin ≤1.5 mg/dL (25μmol/L), and AST (SGOT)/ ALT (SGPT) ≤2 x ULN
or if hepatic metastases are present ≤ 5 x ULN.
9. No other trial: Patient is not participating any other clinical intervention 28 days
before start of trial medication until study conclusion.
10. Women of childbearing potential (see Annex 1): A negative pregnancy test & effective
contraception are mandatory in child-bearing age.
- A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has
not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been
naturally postmenopausal for at least 24 consecutive months (i.e., has had
menses at any time in the preceding 24 consecutive months).
- A FCBP potential must have a negative serum or urine pregnancy test with a
sensitivity of at least 50 mU/mL within 10 to 14 days prior to and again within
24 hours of prescribing lenalidomide (prescriptions must be filled within 7
days) and must either commit to continued abstinence from heterosexual
intercourse or begin TWO acceptable methods of birth control, one highly
effective method and one additional effective method AT THE SAME TIME, at least
28 days before she starts taking lenalidomide.
- FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex
condom during sexual contact with a FCBP even if they have had a successful
vasectomy. See (Annex 2): Risks of Fetal Exposure, Pregnancy Testing Guidelines
and Acceptable Birth Control Methods.
11. Cognition: Presence of a normal level of consciousness (mandatory is a normal
abbreviated screening mini-mental test or a common mini-mental ≥ 27/30; in elderly
patients age ≥ 65 years or patients with low education a mini mental status of ≥25/30
points will be considered adequate).
12. Logistics: The patient is able to comply with the study schedule and procedures
(including fasting for blood draws on certain visits)
13. Consent: The patient has voluntarily signed and dated the informed consent (IC),
approved by the Ethics Committee (EC), prior to any study-specific procedures.
- Will consent to the use of asprin (100mg) or low molecular weight heparin (if
intolerant to aspirin) in prophylactic dose (e.g. Fragmin 2500U sc od).
- Study participant agrees to be registered in the mandatory RevAssist® program,
and be willing and able to comply with the requirements of RevAssist®.(Appendix
1. Untreated secondary causes of cachexia (oral thrush, nausea, vomiting, constipation,
diarrhoea, pain VAS>3, depression, dyspnoea)
2. CTCAEv3.0 ≥ grade 2 due to anticancer treatment (chemotherapy, radiotherapy or
3. Any psychiatric disorder, alcohol and illicit drug abuse or language problem that
would prevent the patient from filling in the questionnaires adequately or attend
study visits according to protocol.
4. Parenteral nutrition
5. Presence of dysthyreosis, defined as TSH beyond normal ranges
6. Presence of long QT syndrome or QTc > 450ms or under treatment with a QT prolonging
7. Presence of lactose intolerance
8. Diabetes mellitus with secondary organ dysfunction (coronary heart disease, previous
stroke, renal insufficiency)
9. Patients with cerebral metastases or prophylactic whole brain irradiation for
possible cerebral metastases.
10. Known hypersensitivity to thalidomide or a history of development of erythema nodosum
due to thalidomide or similar drugs.
11. Any prior use of lenalidomide
12. Known infection with HIV, hepatitis B or C
13. Patients with known myeloid malignancy or tumours having bone marrow involvement.
14. Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study.
15. Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent (IC) form.
16. Pregnant or breastfeeding females.