Individual Dose-escalated Bi-daily Subcutaneously (sc) Ghrelin in Cancer Cachexia: a Phase I/II Study

Inclusion:

• Age: Patients must be older than 18 years of age
• Tumour situation: Patients with any type of advanced (defined as locally recurrent or metastatic), incurable solid tumour.
• Cachexia: defined as involuntary loss of weight of ≥2% in 2 months or ≥5% in 6 months, and ongoing in the last 4 weeks
• No simple starvation: Patients must be able to eat, defined as no severe structural barriers in the upper gastrointestinal tract and no bowel obstruction.
• No late cachexia: Patient must have an expected life expectancy > 3 months
• No anti-cachexia or appetite-stimulating medications: Patients are not allowed to have corticosteroids unless for maximum 2 days for chemotherapy, no progestin therapy within the last 2 weeks, no anabolic drugs within the last month. 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.
• Laboratory test results within these ranges: Absolute neutrophil 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.
• No other trial: Patient is not or was not participating in any other clinical trial within 28 before visit 2.
• Women of childbearing potential: A negative pregnancy test & effective contraception are mandatory in child-bearing age.
• Men agree not to father a child (i.e. use adequate birth control if sexually active) during participation in the trial.
• 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).
• Consent: The patient has voluntarily signed and dated an independent Ethics Committee (IEC) approved consent prior to any study-specific procedures.
• Gastrectomy: Patients with history of gastrectomy are eligible.

Exclusion:

• Questionnaires: Any psychiatric disorder, alcohol and illicit drug abuser language problem that would prevent the patient from filling in the questionnaires adequately.
• Patient with a history of psychiatric diagnosis of depression or clinical diagnosis of depression as determined by the treating physician or Hospital Anxiety Depression Scale total score of 13 or greater.
• History of alcohol abuse as determined by the CAGE questionnaire (≥2/4) or history of illicit drug abuse within last 12 months.
• Parenteral nutrition
• Diabetes mellitus with secondary organ dysfunction: coronary heart disease, previous stroke, renal insufficiency
• Patients with cerebral metastases or prophylactic whole brain irradiation for possible cerebral metastases.
• Known hypersensitivity to ghrelin.
• Known infection with HIV or a viral hepatitis
• Patients with known myeloid malignancy or tumours having bone marrow involvement
• 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.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.