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Completed

NCT Number: NCT01614990

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

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.

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Key information

Conditions

Cancer Cachexia

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Veterans Affairs Puget Sound Health Care System

Seattle, Washington, 98108, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Subjects ≥18 years of age with histological diagnosis of incurable cancer (solid tumor),
  • ECOG performance status of 0-2,
  • 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
  • Provide written informed consent prior to screening.

Exclusion criteria

  • Obesity (body weight >140 Kg);
  • Recent active excessive alcohol or illicit drug use;
  • Severe depression as determined by the investigator;
  • 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, severe COPD requiring use of home O2;
  • Inability to increase food intake (e.g., esophageal obstruction, intractable nausea and vomiting);
  • Any condition that would prevent the subject from performing the research procedures (e.g. unstable coronary artery disease);
  • 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;
  • Recent administration (less than 1 week) of highly emetogenic chemotherapy (Hesketh scale class 4-5); subjects may otherwise be undergoing chemotherapy.
  • 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.
  • Co-administration of drugs that prolong QT interval, CYP3A4 inducers, QTc equal to or greater than 450ms at screening, 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).
  • 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.

Treatment and study plan

Macimorelin

Drug

Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.

Other names: AEZS-130

Placebo

Drug

placebo (Powerade®) daily for 7 days.

Other names: Powerade®

Primary outcomes

  1. Change of Body Weight

    Time frame: 7 days

    The change of body weight(kg)will be measured between day 1 and day (Day 7-Day 1).

  2. Change of Insulin-like Growth Factor-1 (IGF-1) Plasma Levels

    Time frame: 7 days

    The change of IGF-1 plasma levels will be measured between day 1 (prior to dosing) and day 7.

  3. Change of Quality of Life Score

    Time frame: 7 days

    The change of quality of life score (Anderson Symptom Assessment Scale [ASAS; absolute score], Functional Assessment of Chronic Illness-Fatigue [FACIT-F; total score]) will be measured between day 1 and day 7. The ASAS is a validated measure of quality of life (QOL) associated with symptom clusters commonly seen in cancer patient populations. The absolute score ranges from 0-100 with higher scores indicative of worse cancer symptoms. The FACIT-F is a validated measure of QOL associated with fatigue related to chronic illness. To account for missing items, the FACIT-F total score (sum of subscales) was adjusted by calculating the percent total score of items completed with the following:

    (FACIT-F Total Score)/(N items completed ×4 (maximum possible score for each item ) × 100% Scores range from 0 to 160 with higher scores indicative of greater fatigue. Tests consists of 5 subscales: Physical, Social/Family, Emotional, and Functional Well-Being, and Additional Concerns.

Secondary outcomes

  1. Food Intake and Diary

    Time frame: 7 days

    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.

  2. Appetite (Visual Analog Scale [VAS] for Appetite)

    Time frame: 7 days

    Change of appetite measured by a validated visual analogue scale between day 1 and day 7. The VAS is a one-item measure that quantifies subjective rating with a 100 mm line anchored at 0 mm with the words "Not at all" and at 100 mm with the word "Extremely" where the participant makes a mark on the line indicative of their current hunger level. Higher scores are indicative of greater perceived hunger.

  3. Handgrip Strength

    Time frame: 7 days

    Change in muscle strength as measured by handgrip strength.

  4. Energy Expenditure as Measured by Indirect Calorimetry.

    Time frame: 7 days

    Change in energy expenditure as measured by indirect calorimetry.

  5. Laboratory Assays

    Time frame: Day 1 to Day 7

    Change in Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3), Highly Sensitive C-Reactive Protein (CRP), and glucose between day 1 and day 7.

  6. Safety Laboratory (White Blood Cells)

    Time frame: Day 1 to Day 7

    Change in Clinical laboratory parameters: complete blood count (CBC)

  7. ECG

    Time frame: Day 1 to Day 7

    Change in electrocardiogram (ECG) at days 1 and 7 before and 1 hour after dosing and on the post-study visit.

  8. Number of Participants With Adverse Events as a Measure of Safety and Tolerability

    Time frame: 7 days

    Recording of any adverse events from day 1 to day 7.

  9. Change in Stair Climbing Power (SCP)

    Time frame: Day 1 to Day 7

    SCP was assessed on Day 1 & 7. Participants were asked to climb a standard flight of hospital stairs (13 steps, 15.3 cm each) as quickly as possible, using the handrail if necessary. Two-three trials were attempted with one minute of rest in-between. The shortest completion time was transformed into power and used for analysis where:

    W= (body mass (kg) × acceleration of gravity (9.81 m⁄s^2 )× vertical distance (1.99 m))/(time (seconds))

  10. Change in Percent Predicted Resting Energy Expenditure (REE)

    Time frame: Day 1 to Day 7

    Change in percent predicted (REE) as measured by indirect calorimetry.

  11. Change in Respiratory Quotient

    Time frame: Day 1 to Day 7

    Change in respiratory quotient (the ratio of volume CO2 released to volume of O2 utilized) as measured by indirect calorimetry.

  12. Laboratory Assays (Growth Hormone)

    Time frame: Day 1 to Day 7

    Change in Growth Hormone (GH) between day 1 and day 7.

  13. Safety Laboratory (Red Blood Cells)

    Time frame: Day 1 to Day 7

    Change in Clinical laboratory parameters: complete blood count (CBC)

  14. Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin)

    Time frame: Day 1 to Day 7

    Change in Clinical laboratory parameters: complete blood count (CBC) and complete metabolic panel

  15. Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil)

    Time frame: Day 1 to Day 7

    Change in Clinical laboratory parameters: complete blood count (CBC)

  16. Safety Laboratory (Mean Corpuscular Volume [MCV])

    Time frame: Day 1 to Day 7

    Change in Clinical laboratory parameters: complete blood count (CBC)

  17. Safety Laboratory (Mean Corpuscular Hemoglobin [MCH])

    Time frame: Day 1 to Day 7

    Change in Clinical laboratory parameters: complete blood count (CBC)

  18. Safety Laboratory (Platelet)

    Time frame: Day 1 to Day 7

    Change in Clinical laboratory parameters: complete blood count (CBC)

  19. Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium)

    Time frame: Day 1 to Day 7

    Change in Clinical laboratory parameters: complete metabolic panel

  20. Safety Laboratory (Sodium; Chloride; Carbon Dioxide)

    Time frame: Day 1 to Day 7

    Change in Clinical laboratory parameters: complete metabolic panel

  21. Safety Laboratory (Potassium)

    Time frame: Day 1 to Day 7

    Change in Clinical laboratory parameters: complete metabolic panel

  22. Safety Laboratory (Alkaline Phosphatase)

    Time frame: Day 1 to Day 7

    Change in Clinical laboratory parameters: complete metabolic panel

  23. Safety Laboratory (Estimated Glomerular Filtration Rate [eGFR])

    Time frame: Day 1 to Day 7

    Change in Clinical laboratory parameters: complete metabolic panel

  24. Safety Laboratory (Alanine Transaminase [ALT]; Aspartate Aminotransferase [AST])

    Time frame: Day 1 to Day 7

    Change in Clinical laboratory parameters: complete metabolic panel

  25. ECG (Heart Rate [HR])

    Time frame: Day 1 to Day 7

    Change in electrocardiogram (ECG) at days 1 and 7 before and 1 hour after dosing and on the post-study visit.

Sponsors and collaborators

Lead sponsor

Garcia, Jose M., MD, PhD

Indiv

Collaborators

  • AEterna Zentaris
  • Baylor College of Medicine
  • VA Office of Research and Development

Registry information

Important dates

Study start
2012
Primary completion
2020
Study completion
2021
First posted
Jun 8, 2012
Registry last updated
Mar 20, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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