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)

A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter 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)

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.

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer; Cachexia; Cancer
• Intervention / Treatment: Drug: Anamorelin Hydrochloride; Drug: Placebo Oral Tablet

Detailed Description

The study was a multicenter, randomized, double-blind, parallel-group, placebo controlled study to evaluate the efficacy and safety of anamorelin HCl. It was planned that approximately 316 patients with advanced NSCLC with cachexia were to be randomized 1:1 to anamorelin HCl 100 mg or placebo (158 patients per treatment group). The study treatment was to be taken orally once daily for a total of 24 weeks. Patients were instructed to take the study drug at least 1 hour before their first meal of the day.

Central randomization was stratified by line of systemic anti-cancer treatment (first line vs second line vs third line or higher), by type of anti-cancer therapy (immunotherapy vs non-immunotherapy), and by baseline score of the 5-item Anorexia Symptom Subscale (5-IASS) (≤10 vs >10).

Patients who had never received anti-cancer treatment prior to entering the study but who met all eligibility criteria were eligible to enter the study and were assigned to receive first line treatment in the Interactive Web Response System (IWRS).

Patients were to visit the site every 3 weeks for the study Treatment Period of 24 weeks. A follow-up telephone visit was to be scheduled at Week 26. Thus, patients were enrolled in the study for a maximum duration of 27 weeks (including a 1-week Screening Period, a 24-week Treatment Period, and a 2-week Follow-up Period). Each patient was scheduled to have a total of 10 planned visits plus 1 telephone contact for the Follow-up Visit.

• Study Type: Interventional
• Enrollment (Actual): 318
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Burgas, Bulgaria, 8000
    • Department of Medical Oncology, Complex Oncology Center - Burgas, Burgas
  • Dobrich, Bulgaria, 9300
    • Department of Medical Oncology, Multiprofile Hospital for Active Treatment - Dobrich, Dobrich
  • Gabrovo, Bulgaria, 5300
    • Department of Medical Oncology, Multiprofile Hospital for Active Treatment
  • Sofia, Bulgaria, 1407
    • Department of Medical Oncology, Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda, Sofia
  • Varna, Bulgaria, 9010
    • Clinic of Medical Oncology, Hospital Sveta Marina
  • Varna, Bulgaria, 9010
    • Clinic on Medical Oncology University Multiprofile Hospital for Active Treatment "Sveta Marina", Varna
• Hungary
  • Budapest, Hungary, H-1121
    • Koranyi National Institute of Pulmonology, 6th Department of Pulmonology
  • Debrecen, Hungary, H-4032
    • University of Debrecen Clinical Center, Department of Pulmonology
  • Farkasgyepű, Hungary, 1-1-8582
    • Veszprem County Pulmonology Institute
  • Pécs, Hungary, H-7623
    • Clinical Center of the University of Pecs, Department of Pulmonology
  • Szekesfehervar, Hungary, H-8000
    • Fejer County St. Gyorgy University Teaching Hospital, Pulmonology Department I
  • Szolnok, Hungary, H-5000
    • Jasz-Nagy Kun-Szolnok County Hetenyi Geza Hospital-Clinic, Department of Oncology
  • Törökbálint, Hungary, H - 2045
    • Pulmonology Institute Torokbalint
• Italy
  • Aviano, Italy, 33081
    • Oncology Reference Center
  • Monza, Italy, 20900
    • Local Healthcare Company of Monza (ASST Monza)
  • Napoli, Italy, 80131
    • AOU University Luigi Vanvitelli Oncohematology Department
  • Rom, Italy, 00168
    • University Policlinic Fondation Agostino Gemelli
  • Roma, Italy, 00185
    • Umberto I Policlinico la Sapienza, Translational and Precision Medicine Department
  • Ferrara
    • Cona, Ferrara, Italy, 44124
      • University Hospital of Ferrara, Oncology Department
  • Forli
    • Meldola, Forli, Italy, 47014
      • Scientific Institute of Romagna for the Study and Treatment of Cancer (IRST)
  • Italia
    • Legnago, Italia, Italy, 37045
      • Hospital Mater Salutis
    • Lido Di Camaiore, Italia, Italy, 55049
      • Versilia Hospital
    • Piacenza, Italia, Italy, 29121
      • Hospital "Guglielmo da Saliceto"
• Romania
  • Bihor
    • Oradea, Bihor, Romania, 410469
      • S.C. Pelican Impex S.R.L
  • Cluj
    • Cluj Napoca, Cluj, Romania, 400641
      • Medisprof S.R.L
  • Dolj
    • Craiova, Dolj, Romania, 200094
      • S.C. Onco Clinic Consult SA
  • Mures
    • Targu Mures, Mures, Romania, 540 141
      • Mures County Clinical Hospital
  • Prahova
    • Ploiesti, Prahova, Romania, 100337
      • Ploiesti Municipal Hospital
  • Timis
    • Timisoara, Timis, Romania, 300166
      • Oncocenter - Oncologie Clinica SRL
• Russian Federation
  • Chelyabinsk, Russian Federation, 454048
    • Evimed, LLC
  • Ivanovo, Russian Federation, 153040
    • lvanovo Regional Oncology Center
  • Izhevsk, Russian Federation, 426009
    • Primushko Republicun Clinical Oncology Center
  • Kaliningrad, Russian Federation, 236016
    • Immanuel Kant Baltic Federal University
  • Kursk, Russian Federation, 305524
    • Kursk Regional Clinical Oncology Center
  • Moscow, Russian Federation, 121467
    • University Headache Clinic
  • Moscow, Russian Federation, 121 309
    • YitaMed, LLC
  • Omsk, Russian Federation, 644013
    • Clinical Oncology Center
  • Omsk, Russian Federation, 644046
    • Clinical Oncology Center
  • Saint Petersburg, Russian Federation, 197022
    • First I.P. Pavlov State Medical University of St. Petersburg
  • Saint Petersburg, Russian Federation, 198207
    • City Outpatient Clinic #43
  • Tambov, Russian Federation, 392013
    • Tambov Regional Oncological Clinical Center
  • Tomsk, Russian Federation, 634028
    • Tomsk National Research Medical Center
  • Kaluga Region
    • Obninsk, Kaluga Region, Russian Federation, 249036
      • National Medical Research Radiological Centre (Tsyb Medical Radiology Research Center)
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia, Clinic of Pulmonology
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center l\emnijsJca kosa
  • Belgrade, Serbia, 11000
    • Medical Military Academy
  • Belgrade, Serbia, 11000
    • Oncomed-System, Specialized Hospital for Internal Diseases
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
• United States
  • Arizona
    • Tucson, Arizona, United States, 85745
      • Chen
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • CARTI Cancer Center
  • California
    • Riverside, California, United States, 92506
      • The Oncology Insitute of Hope and Innovation
  • Connecticut
    • Plainville, Connecticut, United States, 06062
      • Hartford HealthCare Cancer Institute at The Hospital of Central Connecticut
  • Florida
    • Jacksonville, Florida, United States, 32204
      • 21st Century Oncology
    • Orange City, Florida, United States, 32763
      • Mid Florida Hematology and Oncology Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology Hematology Associates, Ltd
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Goshen Center for Cancer Care
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic, PC
    • Waterloo, Iowa, United States, 50702
      • MercyOne Waterloo Cancer Center
  • Minnesota
    • Jackson, Minnesota, United States, 39216
      • Jackson Oncology Associates, PLC
  • New Jersey
    • Elizabeth, New Jersey, United States, 07207
      • Trinitas Comprehensive Cancer Center/Trinitas Regional Medical Center
    • Englewood, New Jersey, United States, 07631
      • Englewood Health
  • New York
    • Johnson City, New York, United States, 13790
      • Broome Oncology LLC
    • Lake Success, New York, United States, 11042
      • Northwell Health
    • Stony Brook, New York, United States, 11794
      • Stony Brook Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Wexner Medical Center The James Cancer Hospital and Solove Research Institute
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
      • Gettysburg Cancer Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Tennessee Cancer Specialist
  • Utah
    • Ogden, Utah, United States, 84405
      • Community Cancer Trial of Utah
  • Virginia
    • Richmond, Virginia, United States, 23298-0230
      • Virginia Commonwealth University, Massey Cancer Center
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital & Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed written informed consent
2. Female or male ≥18 years of age
3. Documented histologic or cytologic diagnosis of American Joint Committee on Cancer (AJCC) Stage III or IV NSCLC. Stage III patient must have unresectable disease
4. Body mass index < 20 kg/m2 with involuntary weight loss of >2% within 6 months prior to screening
5. 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

6. 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:

   1. 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
   2. 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
   3. Patient on palliative care treatment
7. ECOG performance status 0,1 or 2 at screening
8. AST (SGOT) and ALT (SGPT) ≤ 3 x ULN or if hepatic metastases are present ≤ 5 x ULN
9. Adequate renal function, defined as creatinine ≤2 ULN, or calculated creatinine clearance >30 ml/minute

10. 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:

    1. Female patient of non-childbearing potential are defined as being in post-menopausal state since at least 1 year; or having documented surgical sterilization or hysterectomy at least 3 months before study participation.
    2. Reliable contraceptive measures include implants, injectables, combined oral contraceptives, intrauterine devices, vasectomized partner or complete (long term) sexual abstinence.
11. The patient must be willing and able to comply with the protocol tests and procedures.

All inclusion criteria were to be checked at screening visit (Visit 1). Inclusion criterion #10 was to be re-checked and verified at Day 1 (Visit 2).

Exclusion Criteria:

1. Patient with other forms of lung cancer (e.g., small cell, neuroendocrine tumors)
2. Woman who is pregnant or breast-feeding

3. Reversible causes of reduced food intake, as determined by the Investigator. These causes may include but are not limited to:

   1. NCI CTCAE Grade 3 or 4 oral mucositis,
   2. NCI CTCAE Grade 3 or 4 GI disorders [nausea, vomiting, diarrhea, and constipation],
   3. mechanical obstructions making patient unable to eat, or
   4. severe depression
4. 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.
5. 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
6. Patient with pleural effusion requiring thoracentesis, pericardial effusion requiring drainage, edema or evidence of ascites

7. Patient with uncontrolled or significant cardiovascular disease, including:

   1. History of myocardial infarction within the past 3 months
   2. A-V block of second or third degree (may be eligible if currently have a pacemaker)
   3. Unstable angina
   4. Congestive heart failure within the past 3 months, if defined as NYHA class III-IV
   5. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, Wolff-Parkinson-White (WPW) syndrome, or torsade de pointes)
   6. Uncontrolled hypertension (blood pressure >150 mm Hg systolic and >95 mm Hg diastolic)
   7. Heart rate < 50 beats per minute on pre-entry electrocardiogram and patient is symptomatic
8. Patient on drugs that may prolong the PR or QRS interval durations, such as any of the antiarrhythmic medications Class I (Fast sodium (Na) channel blockers)
9. Patient unable to readily swallow oral tablets
10. Patient with severe gastrointestinal disease (including esophagitis, gastritis, malabsorption)
11. Patient with history of gastrectomy
12. Patient with uncontrolled diabetes mellitus or unmonitored diabetes mellitus

13. Patient with cachexia caused by other reasons, as determined by the investigator such as:

    1. Severe COPD requiring use of home O2,
    2. New York Heart Association (NYHA) class III-IV heart failure
    3. AIDS
    4. Uncontrolled thyroid disease
14. Patient receiving strong CYP3A4 inhibitors within 14 days of randomization
15. Patient currently receiving tube feedings or parenteral nutrition (either total or partial).
16. Current excessive alcohol or illicit drug use
17. Any condition, including the presence of laboratory abnormalities, which in the Investigator's opinion, places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
18. Enrollment in a previous study with anamorelin HCl
19. Patient actively receiving a concurrent investigational agent, or having received an investigational agent within 28 days of Day 1

All exclusion criteria were to be checked at screening visit (Visit 1). Exclusion Criteria #3, 5, 6, 7g, and 9 were to be re-checked and verified before study drug administration (Visit 2).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 100 mg anamorelin HCl; 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; 100 mg anamorelin HCl (administered as 100 mg tablets in the fasted condition)
Placebo Comparator: placebo; 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; Placebo (administered as matching placebo tablets in the fasted condition)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in Body Weight (≥0 kg)	The duration of treatment benefit over 12 weeks was measured as the period, or the sum of the periods, over 12 weeks (or less in case of death), in which the patient observed a change from baseline in body weight of ≥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)	The duration of treatment benefit over 12 weeks was measured as the period, or the sum of the periods, over 12 weeks (or less in case of death), in which the patient observed a change from baseline in body weight of ≥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)	The duration of treatment benefit over 12 weeks was measured as the period, or the sum of the periods, over 12 weeks (or less in case of death), in which the patient observed a change from baseline in 5-IASS of ≥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)	The duration of treatment benefit over 12 weeks was measured as the period, or the sum of the periods, over 12 weeks (or less in case of death), in which the patient observed a change from baseline in 5-IASS of ≥3 points.	Duration of treatment benefit from baseline over 12 weeks.

Collaborators and Investigators

• Sponsor: Helsinn Healthcare SA

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2019
• Primary Completion (Actual): February 11, 2023
• Study Completion (Actual): February 11, 2023

Study Registration Dates

• First Submitted: November 14, 2018
• First Submitted That Met QC Criteria: November 14, 2018
• First Posted (Actual): November 15, 2018

Study Record Updates

• Last Update Posted (Actual): June 26, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Signs and Symptoms, Digestive; Body Weight; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Body Weight Changes; Thinness; Anorexia; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Weight Loss; Cachexia
• Other Study ID Numbers: ANAM-17-20; 2018-002926-22 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No