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

Cancer Cachexia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01614990
• Other study ID #: 00954
• Status: Completed
• Phase: Phase 2
• Start date: May 2012
• Est. completion date: December 2021

Study information

• Verified date: March 2024
• Source: Garcia, Jose M., MD, PhD
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 2021
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Cachexia
• Cancer Cachexia

Intervention

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

Locations

Country	Name	City	State
United States	Veterans Affairs Puget Sound Health Care System	Seattle	Washington

Sponsors (4)

Lead Sponsor	Collaborator
Garcia, Jose M., MD, PhD	AEterna Zentaris, Baylor College of Medicine, VA Office of Research and Development

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of Body Weight	The change of body weight(kg)will be measured between day 1 and day (Day 7-Day 1).	7 days
Primary	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
Primary	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	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
Secondary	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
Secondary	Handgrip Strength	Change in muscle strength as measured by handgrip strength.	7 days
Secondary	Energy Expenditure as Measured by Indirect Calorimetry.	Change in energy expenditure as measured by indirect calorimetry.	7 days
Secondary	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
Secondary	Safety Laboratory (White Blood Cells)	Change in Clinical laboratory parameters: complete blood count (CBC)	Day 1 to Day 7
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in Percent Predicted Resting Energy Expenditure (REE)	Change in percent predicted (REE) as measured by indirect calorimetry.	Day 1 to Day 7
Secondary	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
Secondary	Laboratory Assays (Growth Hormone)	Change in Growth Hormone (GH) between day 1 and day 7.	Day 1 to Day 7
Secondary	Safety Laboratory (Red Blood Cells)	Change in Clinical laboratory parameters: complete blood count (CBC)	Day 1 to Day 7
Secondary	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
Secondary	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
Secondary	Safety Laboratory (Mean Corpuscular Volume [MCV])	Change in Clinical laboratory parameters: complete blood count (CBC)	Day 1 to Day 7
Secondary	Safety Laboratory (Mean Corpuscular Hemoglobin [MCH])	Change in Clinical laboratory parameters: complete blood count (CBC)	Day 1 to Day 7
Secondary	Safety Laboratory (Platelet)	Change in Clinical laboratory parameters: complete blood count (CBC)	Day 1 to Day 7
Secondary	Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium)	Change in Clinical laboratory parameters: complete metabolic panel	Day 1 to Day 7
Secondary	Safety Laboratory (Sodium; Chloride; Carbon Dioxide)	Change in Clinical laboratory parameters: complete metabolic panel	Day 1 to Day 7
Secondary	Safety Laboratory (Potassium)	Change in Clinical laboratory parameters: complete metabolic panel	Day 1 to Day 7
Secondary	Safety Laboratory (Alkaline Phosphatase)	Change in Clinical laboratory parameters: complete metabolic panel	Day 1 to Day 7
Secondary	Safety Laboratory (Estimated Glomerular Filtration Rate [eGFR])	Change in Clinical laboratory parameters: complete metabolic panel	Day 1 to Day 7
Secondary	Safety Laboratory (Alanine Transaminase [ALT]; Aspartate Aminotransferase [AST])	Change in Clinical laboratory parameters: complete metabolic panel	Day 1 to Day 7
Secondary	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