Pilot Clinical Trial of Repeated Doses of Macimorelin to Assess Safety and Efficacy in Patients With Cancer Cachexia

This study is currently recruiting participants.
Verified December 2013 by Garcia, Jose M., MD, PhD
Sponsor:
Collaborators:
Baylor College of Medicine
AEterna Zentaris
Information provided by (Responsible Party):
Garcia, Jose M., MD, PhD
ClinicalTrials.gov Identifier:
NCT01614990
First received: June 5, 2012
Last updated: December 3, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to evaluate the safety and efficacy of repeated oral administration of macimorelin at different doses daily for 1 week for the treatment of cancer cachexia.


Condition Intervention Phase
Cancer Cachexia
Drug: Macimorelin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Pilot Clinical Trial of Repeated Doses of Macimorelin to Assess Safety and Efficacy in Patients With Cancer Cachexia

Resource links provided by NLM:


Further study details as provided by Garcia, Jose M., MD, PhD:

Primary Outcome Measures:
  • Change of body weight [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    The change of body weight(kg)will be measured between day 1 and day 7.

  • Change of IGF-1 plasma levels [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    The change of IGF-1 plasma levels will be measured between day 1 (prior to dosing) and day 7.

  • Change of quality of life score [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    The change of quality of life score (Anderson Symptom Assessment Scale, FACIT-F) will be measured between day 1 and day 7.


Secondary Outcome Measures:
  • Food Intake and Diary [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Food intake as measured by a food diary to be recorded for 3 days before days 1 and 7 and by a test meal done at screening and on day 7.

  • Appetite [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Change of appetite measured by a validated visual analogue scale between day 1 and day 7.

  • Body Composition [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Body composition as measured by bio-impedance on days 1 and 7.

  • Muscle strength [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Muscle strength as measured by handgrip strength and stair climbing power.

  • Energy expenditure as measured by indirect calorimetry. [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Energy expenditure as measured by indirect calorimetry.

  • Laboratory Assays [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Change in IGFBP-3, GH, CRP, IL-6, TNF-α and glucose between day 1 and day 7.

  • fMRI [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Changes in reward from food as measured by brain functional Magnetic Resonance Imaging (fMRI).

  • Functional Brain Connectivity [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Changes in functional brain connectivity as assessed by Resting State Functional Connectivity (RSFC) imaging and Diffusion Tensor Imaging (DTI).

  • Safety Laboratory [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Clinical laboratory parameters: complete blood count (CBC), comprehensive metabolic panel (CMP), urinalysis (UA)

  • Vital signs [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
  • ECG [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Electrocardiogram (ECG) at days 1 and 7 before and 1 hour after dosing and on the post-study visit.

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Recording of any adverse events from day 1 to day 7.


Estimated Enrollment: 26
Study Start Date: May 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Macimorelin Drug: Macimorelin
Subjects will receive different doses of macimorelin (0.25, 0.5 or 1 mg/kg) and matching placebo (Powerade®) daily for 7 days.
Other Name: AEZS-130
Placebo Comparator: Placebo Drug: Placebo
placebo (Powerade®) daily for 7 days.
Other Name: Powerade®

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects ≥18 years of age with histological diagnosis of incurable cancer (solid tumor),
  2. ECOG performance status of 0-2,
  3. Presence of cancer-related cachexia defined as an involuntary weight loss of at least 5% of the pre-illness body weight over the previous 6 months, and
  4. Provide written informed consent prior to screening.

Exclusion Criteria:

  1. Obesity (body weight >140 Kg);
  2. Recent active excessive alcohol or illicit drug use;
  3. Severe depression as determined by the investigator;
  4. Other causes of cachexia such as: Liver disease (AST or ALT > 3x normal levels); renal failure (creatinine >1.5 mg/dL), untreated thyroid disease, class III-IV CHF, AIDS, other cancer diagnosed within the past 5 years other than non-melanoma skin cancer, severe COPD requiring use of home O2;
  5. Inability to increase food intake (e.g., esophageal obstruction, intractable nausea and vomiting);
  6. Any condition that would prevent the subject from performing the research procedures (e.g. unstable coronary artery disease);
  7. Use of growth hormone, megestrol, Marinol, or any other anabolic agents, appetite stimulants (including corticosteroids other than dexamethasone at the time of IV chemotherapy administrations), tube feeding, or parenteral nutrition during the 1 month prior to entering the study;
  8. Recent administration (less than 1 week) of highly emetogenic chemotherapy (Hesketh scale class 4-5); subjects may otherwise be undergoing chemotherapy.
  9. Being female and pregnant, breast-feeding or of childbearing potential. (Note: Lack of childbearing potential for female patients is satisfied by: a) being post menopausal; b) being surgically sterile; c) practicing contraception with an oral contraceptive, intra-uterine device, diaphragm, or condom with spermicide for the duration of the study; or d) being sexually inactive. Confirmation that the patient is not pregnant will be established by a negative serum hCG pregnancy test at the time of enrollment.
  10. Co-administration of drugs that prolong QT interval (see appendix XI), CYP3A4 inducers (see appendix XII), or other investigational agents (a wash-out period of five times the half life of drugs that prolong QT will be allowed with approval of prescriber).
  11. Conditions that would preclude from successfully scanning subjects in MRI:

    • Claustrophobia (this would make lying in the scanner very uncomfortable); b. having a pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, or other implants; c. History of Seizures d. History of head injuries resulting in loss of consciousness > 10 minutes.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01614990

Locations
United States, Texas
Michael E. DeBakey Veterans Affairs Medical Center Recruiting
Houston, Texas, United States, 77030
Contact: Jose M Garcia, MD, PhD    713-794-7989    jgarcia1@bcm.edu   
Contact: Gina M Cardwell, LVN, CRC    713-791-1414 ext 6694    cardwell@bcm.edu   
Principal Investigator: Jose M Garcia, MD, PhD         
Sponsors and Collaborators
Garcia, Jose M., MD, PhD
Baylor College of Medicine
AEterna Zentaris
Investigators
Principal Investigator: Jose M Garcia, MD, PhD Baylor College of Medicine and Veterans Affairs
  More Information

No publications provided

Responsible Party: Garcia, Jose M., MD, PhD
ClinicalTrials.gov Identifier: NCT01614990     History of Changes
Other Study ID Numbers: H-27747
Study First Received: June 5, 2012
Last Updated: December 3, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 15, 2014