Clinical trial NCT01614990: Pilot Clinical Trial of Repeated Doses of Macimorelin to Assess Safety and Efficacy in Patients With Cancer Cachexia
Official title: Pilot Clinical Trial of Repeated Doses of Macimorelin to Assess Safety and Efficacy in Patients With Cancer Cachexia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer Cachexia
Lead sponsor: Garcia, Jose M., MD, PhD
Sponsor class: INDIV
Collaborators: name: VA Office of Research and Development
name: Baylor College of Medicine
name: AEterna Zentaris
First posted: 2012-06-08
Enrollment: 15
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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, 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.

Primary outcomes:
measure: Change of Body Weight
timeFrame: 7 days
measure: Change of Insulin-like Growth Factor-1 (IGF-1) Plasma Levels
timeFrame: 7 days
measure: Change of Quality of Life Score
timeFrame: 7 days
Secondary outcomes:
measure: Food Intake and Diary
timeFrame: 7 days
measure: Appetite (Visual Analog Scale [VAS] for Appetite)
timeFrame: 7 days
measure: Handgrip Strength
timeFrame: 7 days
measure: Energy Expenditure as Measured by Indirect Calorimetry.
timeFrame: 7 days
measure: Laboratory Assays
timeFrame: Day 1 to Day 7
measure: Safety Laboratory (White Blood Cells)
timeFrame: Day 1 to Day 7
measure: ECG
timeFrame: Day 1 to Day 7
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: 7 days
measure: Change in Stair Climbing Power (SCP)
timeFrame: Day 1 to Day 7
measure: Change in Percent Predicted Resting Energy Expenditure (REE)
timeFrame: Day 1 to Day 7
measure: Change in Respiratory Quotient
timeFrame: Day 1 to Day 7
measure: Laboratory Assays (Growth Hormone)
timeFrame: Day 1 to Day 7
measure: Safety Laboratory (Red Blood Cells)
timeFrame: Day 1 to Day 7
measure: Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin)
timeFrame: Day 1 to Day 7
measure: Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil)
timeFrame: Day 1 to Day 7
measure: Safety Laboratory (Mean Corpuscular Volume [MCV])
timeFrame: Day 1 to Day 7
measure: Safety Laboratory (Mean Corpuscular Hemoglobin [MCH])
timeFrame: Day 1 to Day 7
measure: Safety Laboratory (Platelet)
timeFrame: Day 1 to Day 7
measure: Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium)
timeFrame: Day 1 to Day 7
measure: Safety Laboratory (Sodium; Chloride; Carbon Dioxide)
timeFrame: Day 1 to Day 7
measure: Safety Laboratory (Potassium)
timeFrame: Day 1 to Day 7
measure: Safety Laboratory (Alkaline Phosphatase)
timeFrame: Day 1 to Day 7
measure: Safety Laboratory (Estimated Glomerular Filtration Rate [eGFR])
timeFrame: Day 1 to Day 7
measure: Safety Laboratory (Alanine Transaminase [ALT]; Aspartate Aminotransferase [AST])
timeFrame: Day 1 to Day 7
measure: ECG (Heart Rate [HR])
timeFrame: Day 1 to Day 7
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Veterans Affairs Puget Sound Health Care System
state: Washington
Study officials:
affiliation: University of Washington and Veterans Affairs Puget Sound Health Care System
name: Jose M Garcia, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.