A Study to Evaluate the Efficacy and Safety of Anamorelin HCl for the Treatment of Malignancy Associated Weight Loss and Anorexia in Adult Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

NCT03743051 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: ANAM-17-202018-002926-22
• Study Type: interventional
• Target: 318
• Locations: 7 countries
• Sites: 72

Brief Summary

The goal of this clinical trial was to compare the efficacy and safety of anamorelin HCl (the investigational drug) to that of placebo (tablet with no drug) in patients with advanced non-small cell lung cancer and cachexia (cancer-related weight loss). The main question it aimed to answer was as follows: Do patients who receive anamorelin HCl gain more body weight and show more improvement in anorexia symptoms than those who receive placebo. Approximately 316 patients were to be enrolled in the study. Of these patients, an equal number were to be assigned to each treatment group (anamorelin HCl or placebo). Participants were to take their assigned study drug by mouth once daily for a total of 24 weeks. During this treatment period, the patients were to visit the clinical study site every 3 weeks for health and other study-related assessments. Two weeks after the last treatment, patients were to receive a follow-up phone call.

Conditions

Cachexia; Cancer; Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Mean Change From Baseline in Body Weight Over 12 Weeks

  This co-primary efficacy endpoint was mean change from baseline in body weight (kg) over 12 weeks in the anamorelin HCl group versus placebo group. Mean change was computed as sum of the changes from baseline over 12 weeks by the time of the last assessment (either week 12 or before in case of death), and then divided by the number of assessments (observed or imputed) from baseline up to the time of the last assessment.

  Mean change from baseline over 12 weeks.

• Mean Change From Baseline in 5-item Anorexia Symptom Subscale (5-IASS) Over 12 Weeks

  This co-primary efficacy endpoint was mean change from baseline in 5-IASS (points) over 12 weeks in the anamorelin HCl group versus placebo group. Mean change was computed as sum of the changes from baseline over 12 weeks by the time of the last assessment (either week 12 or before in case of death), and then divided by the number of assessments (observed or imputed) from baseline up to the time of the last assessment. FAACT-A/CS (Functional Assessment Anorexia Cachexia Therapy) is a 12-item measure of patients' perceptions of anorexia/cachexia symptoms and concerns. From this questionnaire, the 5-item section referring to anorexia symptoms (i.e., "good appetite," "interest in food drops," "food tastes unpleasant," "get full quickly," and "difficulty eating rich/heavy foods") was used to assess 5-IASS. The range of possible scores is 0-20. Higher scores indicate lower levels of symptom burden.

  Mean change from baseline over 12 weeks.

Secondary Outcomes (4)

• Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in Body Weight (≥0 kg)

  Duration of treatment benefit from baseline over 12 weeks.

• Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in Body Weight (≥1.5 kg)

  Duration of treatment benefit from baseline over 12 weeks.

• Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in 5-IASS (≥0 Points)

  Duration of treatment benefit from baseline over 12 weeks.

• Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in 5-IASS (≥3 Points)

  Duration of treatment benefit from baseline over 12 weeks.

Study Arms (2)

100 mg anamorelin HCl

EXPERIMENTAL

100 mg anamorelin HCl (administered as film-coated tablets in fasted condition) was to be taken orally once daily for a total of 24 weeks

Drug: Anamorelin Hydrochloride

placebo

PLACEBO COMPARATOR

Placebo (administered as matching placebo tablets in fasted condition) was to be taken orally once daily for a total of 24 weeks

Drug: Placebo Oral Tablet

Interventions

Anamorelin Hydrochloride DRUG

100 mg anamorelin HCl (administered as 100 mg tablets in the fasted condition)

100 mg anamorelin HCl

Placebo Oral Tablet DRUG

Placebo (administered as matching placebo tablets in the fasted condition)

placebo

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent
• Female or male ≥18 years of age
• Documented histologic or cytologic diagnosis of American Joint Committee on Cancer (AJCC) Stage III or IV NSCLC. Stage III patient must have unresectable disease
• Body mass index \< 20 kg/m2 with involuntary weight loss of \>2% within 6 months prior to screening
• Ongoing problems with appetite/eating associated with the underlying cancer, as determined by having score of ≤ 17 points on the 5-item Anorexia Symptom Scale and ≤ 37 points on the 12-item FAACT A/CS
• Patient receiving or not receiving systemic anti-cancer treatment at the time of screening are eligible to participate. Systemic anti-cancer treatment includes first, second, third treatment line with chemotherapy/radiation therapy, immunotherapy or targeted therapy.
• Patient not receiving systemic anti-cancer treatment is eligible if:
• Not planning to receive anti-cancer treatment and/or at least 14 days must be elapsed from the completion of prior treatment at the day of screening, in case underwent previous cycle OR
• Planning to receive anti-cancer treatment within 14 days from randomization and/or at least 14 days must be elapsed from the completion of prior treatment at the day of screening, in case underwent previous cycle OR
• Patient on palliative care treatment
• ECOG performance status 0,1 or 2 at screening
• AST (SGOT) and ALT (SGPT) ≤ 3 x ULN or if hepatic metastases are present ≤ 5 x ULN
• Adequate renal function, defined as creatinine ≤2 ULN, or calculated creatinine clearance \>30 ml/minute
• Female patient shall be: a) of non-childbearing potential or b) of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test within 24 hours prior to first dose of investigational product.
• Notes:

You may not qualify if:

• Patient with other forms of lung cancer (e.g., small cell, neuroendocrine tumors)
• Woman who is pregnant or breast-feeding
• Reversible causes of reduced food intake, as determined by the Investigator. These causes may include but are not limited to:
• NCI CTCAE Grade 3 or 4 oral mucositis,
• NCI CTCAE Grade 3 or 4 GI disorders \[nausea, vomiting, diarrhea, and constipation\],
• mechanical obstructions making patient unable to eat, or
• severe depression
• Patient undergoing major surgery (central venous access placement and tumor biopsies are not considered major surgery) within 4 weeks prior to randomization. Patient must be well recovered from acute effects of surgery prior to screening. Patient should not have plans to undergo major surgical procedures during the treatment period.
• Patient currently taking androgenic compounds including but not limited to testosterone, testosterone-like agents, oxandrolone; megestrol acetate; corticosteroids; olanzapine, mirtazapine (however, long-term use of mirtazapine for depression for at least four weeks prior to screening is allowed); dronabinol; marijuana (cannabis); or any other prescription medication or off-label products intended to increase appetite or treat unintentional weight loss
• Patient with pleural effusion requiring thoracentesis, pericardial effusion requiring drainage, edema or evidence of ascites
• Patient with uncontrolled or significant cardiovascular disease, including:
• History of myocardial infarction within the past 3 months
• A-V block of second or third degree (may be eligible if currently have a pacemaker)
• Unstable angina
• Congestive heart failure within the past 3 months, if defined as NYHA class III-IV

Sponsors & Collaborators

• Helsinn Healthcare SA: lead

Study Sites (72)

Chen

Tucson, Arizona, 85745, United States

Location

CARTI Cancer Center

Little Rock, Arkansas, 72205, United States

Location

The Oncology Insitute of Hope and Innovation

Riverside, California, 92506, United States

Location

Hartford HealthCare Cancer Institute at the Hospital of Central Connecticut

Plainville, Connecticut, 06062, United States

Location

21st Century Oncology

Jacksonville, Florida, 32204, United States

Location

Mid Florida Hematology and Oncology Center

Orange City, Florida, 32763, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Joliet Oncology Hematology Associates, Ltd

Joliet, Illinois, 60435, United States

Location

Goshen Center for Cancer Care

Goshen, Indiana, 46526, United States

Location

McFarland Clinic, PC

Ames, Iowa, 50010, United States

Location

MercyOne Waterloo Cancer Center

Waterloo, Iowa, 50702, United States

Location

Jackson Oncology Associates, PLC

Jackson, Minnesota, 39216, United States

Location

Trinitas Comprehensive Cancer Center/Trinitas Regional Medical Center

Elizabeth, New Jersey, 07207, United States

Location

Englewood Health

Englewood, New Jersey, 07631, United States

Location

Broome Oncology LLC

Johnson City, New York, 13790, United States

Location

Northwell Health

Lake Success, New York, 11042, United States

Location

Stony Brook Cancer Center

Stony Brook, New York, 11794, United States

Location

Ohio State University Wexner Medical Center The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

Location

Gettysburg Cancer Center

Gettysburg, Pennsylvania, 17325, United States

Location

Tennessee Cancer Specialist

Knoxville, Tennessee, 37909, United States

Location

Community Cancer Trial of Utah

Ogden, Utah, 84405, United States

Location

Virginia Commonwealth University, Massey Cancer Center

Richmond, Virginia, 23298-0230, United States

Location

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, 99336, United States

Location

Wenatchee Valley Hospital & Clinics

Wenatchee, Washington, 98801, United States

Location

Department of Medical Oncology, Complex Oncology Center - Burgas, Burgas

Burgas, 8000, Bulgaria

Location

Department of Medical Oncology, Multiprofile Hospital for Active Treatment - Dobrich, Dobrich

Dobrich, 9300, Bulgaria

Location

Department of Medical Oncology, Multiprofile Hospital for Active Treatment

Gabrovo, 5300, Bulgaria

Location

Department of Medical Oncology, Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda, Sofia

Sofia, 1407, Bulgaria

Location

Clinic of Medical Oncology, Hospital Sveta Marina

Varna, 9010, Bulgaria

Location

Clinic on Medical Oncology University Multiprofile Hospital for Active Treatment "Sveta Marina", Varna

Varna, 9010, Bulgaria

Location

Koranyi National Institute of Pulmonology, 6th Department of Pulmonology

Budapest, H-1121, Hungary

Location

University of Debrecen Clinical Center, Department of Pulmonology

Debrecen, H-4032, Hungary

Location

Veszprem County Pulmonology Institute

Farkasgyepű, 1-1-8582, Hungary

Location

Clinical Center of the University of Pecs, Department of Pulmonology

Pécs, H-7623, Hungary

Location

Fejer County St. Gyorgy University Teaching Hospital, Pulmonology Department I

Székesfehérvár, H-8000, Hungary

Location

Jasz-Nagy Kun-Szolnok County Hetenyi Geza Hospital-Clinic, Department of Oncology

Szolnok, H-5000, Hungary

Location

Pulmonology Institute Torokbalint

Törökbálint, H - 2045, Hungary

Location

University Hospital of Ferrara, Oncology Department

Cona, Ferrara, 44124, Italy

Location

Scientific Institute of Romagna for the Study and Treatment of Cancer (IRST)

Meldola, Forli, 47014, Italy

Location

Hospital Mater Salutis

Legnago, Italia, 37045, Italy

Location

Versilia Hospital

Lido di Camaiore, Italia, 55049, Italy

Location

Hospital "Guglielmo da Saliceto"

Piacenza, Italia, 29121, Italy

Location

Oncology Reference Center

Aviano, 33081, Italy

Location

Local Healthcare Company of Monza (ASST Monza)

Monza, 20900, Italy

Location

AOU University Luigi Vanvitelli Oncohematology Department

Napoli, 80131, Italy

Location

Umberto I Policlinico la Sapienza, Translational and Precision Medicine Department

Roma, 00185, Italy

Location

University Policlinic Fondation Agostino Gemelli

Rome, 00168, Italy

Location

S.C. Pelican Impex S.R.L

Oradea, Bihor County, 410469, Romania

Location

Medisprof S.R.L

Cluj-Napoca, Cluj, 400641, Romania

Location

S.C. Onco Clinic Consult SA

Craiova, Dolj, 200094, Romania

Location

Mures County Clinical Hospital

Târgu Mureş, Mureș County, 540 141, Romania

Location

Ploiesti Municipal Hospital

Ploieşti, Prahova, 100337, Romania

Location

Oncocenter - Oncologie Clinica SRL

Timișoara, Timiș County, 300166, Romania

Location

National Medical Research Radiological Centre (Tsyb Medical Radiology Research Center)

Obninsk, Kaluga Oblast, 249036, Russia

Location

Evimed, LLC

Chelyabinsk, 454048, Russia

Location

lvanovo Regional Oncology Center

Ivanovo, 153040, Russia

Location

Primushko Republicun Clinical Oncology Center

Izhevsk, 426009, Russia

Location

Immanuel Kant Baltic Federal University

Kaliningrad, 236016, Russia

Location

Kursk Regional Clinical Oncology Center

Kursk, 305524, Russia

Location

YitaMed, LLC

Moscow, 121 309, Russia

Location

University Headache Clinic

Moscow, 121467, Russia

Location

Clinical Oncology Center

Omsk, 644013, Russia

Location

Clinical Oncology Center

Omsk, 644046, Russia

Location

First I.P. Pavlov State Medical University of St. Petersburg

Saint Petersburg, 197022, Russia

Location

City Outpatient Clinic #43

Saint Petersburg, 198207, Russia

Location

Tambov Regional Oncological Clinical Center

Tambov, 392013, Russia

Location

Tomsk National Research Medical Center

Tomsk, 634028, Russia

Location

Clinical Center of Serbia, Clinic of Pulmonology

Belgrade, 11000, Serbia

Location

Clinical Hospital Center l\emnijsJca kosa

Belgrade, 11000, Serbia

Location

Medical Military Academy

Belgrade, 11000, Serbia

Location

Oncomed-System, Specialized Hospital for Internal Diseases

Belgrade, 11000, Serbia

Location

Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

MeSH Terms

Conditions

Cachexia; Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

anamorelin

Condition Hierarchy (Ancestors)

Weight Loss; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Thinness; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Florin Muraru
• Organization: Helsinn Healthcare SA

florin.muraru@helsinn.com

+41 91985 21 21

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This was a double-blind study. The blinding of the study drugs was guaranteed by the use of anamorelin HCl film-coated tablets and matching placebo tablets. Patients were randomized using the Interactive Web Response System (IWRS). Any unblinding of the study treatment was performed using the IWRS.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blind, Placebo-Controlled, Multicenter Study

Study Record Dates

• First Submitted: November 14, 2018
• First Posted: November 15, 2018
• Study Start: March 5, 2019
• Primary Completion: February 11, 2023
• Study Completion: February 11, 2023
• Last Updated: June 26, 2024
• Results First Posted: June 26, 2024

Record last verified: 2024-06

Locations

IT (10); RU (14); SE (5); RO (6); BU (6); HU (7); US (24)