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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by Cantonal Hospital of St. Gallen.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Bachem
Information provided by:
Cantonal Hospital of St. Gallen
ClinicalTrials.gov Identifier:
NCT00933361
First received: July 6, 2009
Last updated: August 26, 2011
Last verified: July 2009
  Purpose

Cachexia, a condition of severe malnutrition, negative nitrogen balance, muscle wasting, weight loss, and anorexia, is a frequent affecting more than 80% of patients in advanced cancer disease causing a high burden on patients and their families. Nutritional, pharmacological, and behavioural interventions for cancer-related ACS and associated symptoms have, despite the importance for cancer care, limited effect on only a minority of patients. New strategies are required.

Ghrelin, a 28 amino acid peptide discovered in 1999, is predominantly secreted by gastric endocrine cells and is an endogenous ligand for the growth hormone secretagogue (GHS) receptor. When administered peripherally it stimulates growth hormone secretion, food intake, triggers a positive energy balance, produces weight gain through a central mechanism involving hypothalamic neuropeptides and has anti-inflammatory effects. A recently completed trial on intravenous ghrelin in advanced cancer patients with ACS reports good tolerability and safety of single intravenous application of 2 and 8μg/kg Ghrelin.

Given the facts that ACS is a major burden in patients suffering advanced cancer disease and ghrelin is a major signal for stimulating food intake, promoting positive energy balance and weight gain and may have anti-inflammatory effect it remains to be determined whether the administration of ghrelin will have a positive clinical effect on cancer anorexia/ cachexia syndrome ACS. The next logical clinical development step is a proper dose-finding study of twice daily subcutaneous administration and proof-of-concept of main outcomes.


Condition Intervention Phase
Advanced Cancer
Cachexia
Drug: ghrelin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Individual Dose-escalated Bi-daily sc Ghrelin in Cancer Cachexia: a Phase I/II Study

Resource links provided by NLM:


Further study details as provided by Cantonal Hospital of St. Gallen:

Primary Outcome Measures:
  • To assess the dose of ghrelin in tumour patients with ACS causing optimal stimulation of nutritional intake - minimal dose for maximal nutritional intake (MD-MANI) - or the maximally tolerable dose (MTD), which one occurs first [ Time Frame: bi-weekly ] [ Designated as safety issue: Yes ]
  • To assess the effect of ghrelin on muscle strength. [ Time Frame: weekly ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess the toxicity and tolerability, pharmacokinetics and symptoms of eating of ghrelin. [ Time Frame: bi-weekly ] [ Designated as safety issue: Yes ]
  • To assess the effect of ghrelin on muscle mass, physical function, safety, toxicity and tolerability, pharmacokinetics, symptoms of eating, gastrointestinal motility, inflammation [ Time Frame: weekly ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 12
Study Start Date: June 2009
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ghrelin
Ghrelin, a 28 amino acid peptide discovered in 1999, is predominantly secreted by gastric endocrine cells and is an endogenous ligand for the growth hormone secretagogue (GHS) receptor. When administered peripherally it stimulates growth hormone secretion, food intake, triggers a positive energy balance, produces weight gain through a central mechanism involving hypothalamic neuropeptides and has anti-inflammatory effects
Drug: ghrelin
As starting dose the investigators choose a dose level which was shown in our last study to be safe in human beings, i.e. 8μg/kg intravenously. With an assumed bioavailability of 25% of subcutaneously administered ghrelin the corresponding dose for dose level 1 is therefore 32 μg/kg. In the first 4 dose levels for each subsequent dose level the dose is increased by 50% compared to the previous one, from the 5th dose level onwards the increase is 25%: Dose level 1 = 32 μg/kg Dose level 2 = 48 μg/kg Dose level 3 = 72 μg/kg Dose level 4 = 108 μg/kg Dose level 5 = 135 μg/kg Dose level 6 = 169 μg/kg Dose level 7 = 211 μg/kg The investigators define the maximum tolerable dose as 20mg ghrelin (equivalent to 5ml) for reasons of the high drug volume to be administered subcutaneously.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00933361

Contacts
Contact: Florian Strasser, PD Dr. MD +41 71 494 11 11 (11 79), florian.strasser@kssg.ch

Locations
Switzerland
Cantonal Hospital St. Gallen KSSG Recruiting
St. Gallen, Switzerland, 9000
Sub-Investigator: Blum David, MD         
Sponsors and Collaborators
Cantonal Hospital of St. Gallen
Bachem
Investigators
Principal Investigator: Florian Strasser, PD Dr. MD Cantonal Spital St. Gallen
  More Information

Publications:
Responsible Party: PD Dr. Florian Strasser, MD ABHPM, Cantonal Hospital of St. Gallen
ClinicalTrials.gov Identifier: NCT00933361     History of Changes
Other Study ID Numbers: SG 294/08
Study First Received: July 6, 2009
Last Updated: August 26, 2011
Health Authority: Switzerland: Swissmedic

Keywords provided by Cantonal Hospital of St. Gallen:
Adult

Additional relevant MeSH terms:
Cachexia
Body Weight
Body Weight Changes
Emaciation
Signs and Symptoms
Weight Loss

ClinicalTrials.gov processed this record on November 20, 2014