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.

Study Overview

• Status: Completed
• Conditions: Cancer Cachexia
• Intervention / Treatment: Drug: Macimorelin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98108
      • Veterans Affairs Puget Sound Health Care System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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, 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, 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).

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; placebo (Powerade®) daily for 7 days.; Other Names: Powerade®
Active Comparator: Macimorelin	Drug: Macimorelin; Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.; Other Names: AEZS-130

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Body Weight	The change of body weight(kg)will be measured between day 1 and day (Day 7-Day 1).	7 days
Change of Insulin-like Growth Factor-1 (IGF-1) Plasma Levels	The change of IGF-1 plasma levels will be measured between day 1 (prior to dosing) and day 7.	7 days
Change of Quality of Life Score	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.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Food Intake and Diary	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.	7 days
Appetite (Visual Analog Scale [VAS] for Appetite)	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.	7 days
Handgrip Strength	Change in muscle strength as measured by handgrip strength.	7 days
Energy Expenditure as Measured by Indirect Calorimetry.	Change in energy expenditure as measured by indirect calorimetry.	7 days
Laboratory Assays	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.	Day 1 to Day 7
Safety Laboratory (White Blood Cells)	Change in Clinical laboratory parameters: complete blood count (CBC)	Day 1 to Day 7
ECG	Change in electrocardiogram (ECG) at days 1 and 7 before and 1 hour after dosing and on the post-study visit.	Day 1 to Day 7
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	Recording of any adverse events from day 1 to day 7.	7 days
Change in Stair Climbing Power (SCP)	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))	Day 1 to Day 7
Change in Percent Predicted Resting Energy Expenditure (REE)	Change in percent predicted (REE) as measured by indirect calorimetry.	Day 1 to Day 7
Change in Respiratory Quotient	Change in respiratory quotient (the ratio of volume CO2 released to volume of O2 utilized) as measured by indirect calorimetry.	Day 1 to Day 7
Laboratory Assays (Growth Hormone)	Change in Growth Hormone (GH) between day 1 and day 7.	Day 1 to Day 7
Safety Laboratory (Red Blood Cells)	Change in Clinical laboratory parameters: complete blood count (CBC)	Day 1 to Day 7
Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin)	Change in Clinical laboratory parameters: complete blood count (CBC) and complete metabolic panel	Day 1 to Day 7
Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil)	Change in Clinical laboratory parameters: complete blood count (CBC)	Day 1 to Day 7
Safety Laboratory (Mean Corpuscular Volume [MCV])	Change in Clinical laboratory parameters: complete blood count (CBC)	Day 1 to Day 7
Safety Laboratory (Mean Corpuscular Hemoglobin [MCH])	Change in Clinical laboratory parameters: complete blood count (CBC)	Day 1 to Day 7
Safety Laboratory (Platelet)	Change in Clinical laboratory parameters: complete blood count (CBC)	Day 1 to Day 7
Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium)	Change in Clinical laboratory parameters: complete metabolic panel	Day 1 to Day 7
Safety Laboratory (Sodium; Chloride; Carbon Dioxide)	Change in Clinical laboratory parameters: complete metabolic panel	Day 1 to Day 7
Safety Laboratory (Potassium)	Change in Clinical laboratory parameters: complete metabolic panel	Day 1 to Day 7
Safety Laboratory (Alkaline Phosphatase)	Change in Clinical laboratory parameters: complete metabolic panel	Day 1 to Day 7
Safety Laboratory (Estimated Glomerular Filtration Rate [eGFR])	Change in Clinical laboratory parameters: complete metabolic panel	Day 1 to Day 7
Safety Laboratory (Alanine Transaminase [ALT]; Aspartate Aminotransferase [AST])	Change in Clinical laboratory parameters: complete metabolic panel	Day 1 to Day 7
ECG (Heart Rate [HR])	Change in electrocardiogram (ECG) at days 1 and 7 before and 1 hour after dosing and on the post-study visit.	Day 1 to Day 7

Collaborators and Investigators

• Sponsor: Garcia, Jose M., MD, PhD
• Collaborators: Baylor College of Medicine; VA Office of Research and Development; AEterna Zentaris
• Investigators: Principal Investigator: Jose M Garcia, MD, PhD, University of Washington and Veterans Affairs Puget Sound Health Care System

Publications and helpful links

General Publications

• Maldonado M, Molfese DL, Viswanath H, Curtis K, Jones A, Hayes TG, Marcelli M, Mediwala S, Baldwin P, Garcia JM, Salas R. The habenula as a novel link between the homeostatic and hedonic pathways in cancer-associated weight loss: a pilot study. J Cachexia Sarcopenia Muscle. 2018 Jun;9(3):497-504. doi: 10.1002/jcsm.12286. Epub 2018 Mar 25.
• Herodes M, Anderson LJ, Shober S, Schur EA, Graf SA, Ammer N, Salas R, Marcelli M, Garcia JM. Pilot clinical trial of macimorelin to assess safety and efficacy in patients with cancer cachexia. J Cachexia Sarcopenia Muscle. 2023 Apr;14(2):835-846. doi: 10.1002/jcsm.13191. Epub 2023 Mar 1.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): July 1, 2020
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: June 5, 2012
• First Submitted That Met QC Criteria: June 7, 2012
• First Posted (Estimated): June 8, 2012

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Nutrition Disorders; Body Weight; Body Weight Changes; Weight Loss; Thinness; Wasting Syndrome; Cachexia
• Other Study ID Numbers: 00954