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

Study Overview
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Brief Summary
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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.

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

Conditions
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Cancer Cachexia

Intervention / Treatment
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* Drug: Macimorelin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 7. | 7 days | 
| Change of 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, FACIT-F) will be measured between day 1 and day 7. | 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 | Change of appetite measured by a validated visual analogue scale between day 1 and day 7. | 7 days | 
| Body Composition | Body composition as measured by bio-impedance and dual-energy x-ray absorptiometry on days 1 and 7. | 7 days | 
| Muscle strength | Muscle strength as measured by handgrip strength and stair climbing power. | 7 days | 
| Energy expenditure as measured by indirect calorimetry. | Energy expenditure as measured by indirect calorimetry. | 7 days | 
| Laboratory Assays | Change in IGFBP-3, GH, CRP, IL-6, TNF-α and glucose between day 1 and day 7. | 7 days | 
| fMRI | Changes in reward from food as measured by brain functional Magnetic Resonance Imaging (fMRI). | 7 days | 
| Functional Brain Connectivity | Changes in functional brain connectivity as assessed by Resting State Functional Connectivity (RSFC) imaging and Diffusion Tensor Imaging (DTI). | 7 days | 
| Safety Laboratory | Clinical laboratory parameters: complete blood count (CBC), comprehensive metabolic panel (CMP), urinalysis (UA) | 7 days | 
| Vital signs |  | 7 days | 
| ECG | Electrocardiogram (ECG) at days 1 and 7 before and 1 hour after dosing and on the post-study visit. | 7 days | 
| 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 |