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

NCT01614990 | Completed Phase 2 Results DMC

• 1 other identifier: 00954
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Cancer Cachexia

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (25)

• Food Intake and Diary

  7 days

• Appetite (Visual Analog Scale [VAS] for Appetite)

  7 days

• Handgrip Strength

  7 days

• Energy Expenditure as Measured by Indirect Calorimetry.

  7 days

• Laboratory Assays

  Day 1 to Day 7

Study Arms (2)

Macimorelin

ACTIVE COMPARATOR

Drug: Macimorelin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Macimorelin DRUG

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

Also known as: AEZS-130

Macimorelin

Placebo DRUG

placebo (Powerade®) daily for 7 days.

Also known as: Powerade®

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Garcia, Jose M., MD, PhD: lead
• VA Office of Research and Development: collaborator
• Baylor College of Medicine: collaborator
• AEterna Zentaris: collaborator

Study Sites (1)

Veterans Affairs Puget Sound Health Care System

Seattle, Washington, 98108, United States

Location

Related Publications (2)

• 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.

  PMID: 36860137 RESULT

• 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.

  PMID: 29575771 DERIVED

MeSH Terms

Interventions

macimorelin

Results Point of Contact

• Title: Jose Garcia, MD, PhD
• Organization: Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System

jg77@uw.edu

(206) 764-2984

Study Officials

• Jose M Garcia, MD, PhD

  University of Washington and Veterans Affairs Puget Sound Health Care System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2012
• First Posted: June 8, 2012
• Study Start: May 1, 2012
• Primary Completion: July 1, 2020
• Study Completion: December 1, 2021
• Last Updated: March 20, 2024
• Results First Posted: March 19, 2024

Record last verified: 2024-03

Locations

US (1)