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

• ClinicalTrials.gov Identifier: NCT01614990
• Recruitment Status: Active, not recruiting
• First Posted: June 8, 2012
• Last Update Posted: January 7, 2020
• Sponsor: Garcia, Jose M., MD, PhD
• Collaborators: VA Office of Research and Development; Baylor College of Medicine; AEterna Zentaris
• Information provided by (Responsible Party): Garcia, Jose M., MD, PhD

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cancer Cachexia	Drug: Macimorelin; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Pilot Clinical Trial of Repeated Doses of Macimorelin to Assess Safety and Efficacy in Patients With Cancer Cachexia
• Study Start Date: May 2012
• Estimated Primary Completion Date: July 2020
• Estimated Study Completion Date: December 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change of body weight [ Time Frame: 7 days ]
   The change of body weight(kg)will be measured between day 1 and day 7.
2. Change of 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, FACIT-F) will be measured between day 1 and day 7.

Secondary Outcome Measures :

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 [ Time Frame: 7 days ]
   Change of appetite measured by a validated visual analogue scale between day 1 and day 7.
3. Body Composition [ Time Frame: 7 days ]
   Body composition as measured by bio-impedance and dual-energy x-ray absorptiometry on days 1 and 7.
4. Muscle strength [ Time Frame: 7 days ]
   Muscle strength as measured by handgrip strength and stair climbing power.
5. Energy expenditure as measured by indirect calorimetry. [ Time Frame: 7 days ]
   Energy expenditure as measured by indirect calorimetry.
6. Laboratory Assays [ Time Frame: 7 days ]
   Change in IGFBP-3, GH, CRP, IL-6, TNF-α and glucose between day 1 and day 7.
7. fMRI [ Time Frame: 7 days ]
   Changes in reward from food as measured by brain functional Magnetic Resonance Imaging (fMRI).
8. Functional Brain Connectivity [ Time Frame: 7 days ]
   Changes in functional brain connectivity as assessed by Resting State Functional Connectivity (RSFC) imaging and Diffusion Tensor Imaging (DTI).
9. Safety Laboratory [ Time Frame: 7 days ]
   Clinical laboratory parameters: complete blood count (CBC), comprehensive metabolic panel (CMP), urinalysis (UA)
10. Vital signs [ Time Frame: 7 days ]
11. ECG [ Time Frame: 7 days ]
    Electrocardiogram (ECG) at days 1 and 7 before and 1 hour after dosing and on the post-study visit.
12. 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.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Washington

Veterans Affairs Puget Sound Health Care System

Seattle, Washington, United States, 98108

Sponsors and Collaborators

Garcia, Jose M., MD, PhD

VA Office of Research and Development

Baylor College of Medicine

AEterna Zentaris

Investigators

• Principal Investigator: Jose M Garcia, MD, PhD; University of Washington and Veterans Affairs Puget Sound Health Care System

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Garcia, Jose M., MD, PhD
• ClinicalTrials.gov Identifier: NCT01614990
• Other Study ID Numbers: 00954
• First Posted: June 8, 2012
• Last Update Posted: January 7, 2020
• Last Verified: January 2020

Additional relevant MeSH terms:

Wasting Syndrome; Cachexia; Emaciation; Weight Loss; Body Weight Changes; Body Weight; Metabolic Diseases; Nutrition Disorders