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)

Multicenter, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy and safety of anamorelin HCl. Approximately 316 patients with advanced NSCLC with cachexia will be randomized 1:1 to anamorelin HCl 100 mg or placebo, taken orally once daily (QD) for a total of 24 weeks. Patients will be instructed to take the study drug at least 1 hour before their first meal of the day

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 316
• 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 Acti ve T reatment ··Dr. Tota Venkova" , Gabrovo
  • 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 Muliprofile Hospital for active treatment "Sveta Marina", Varna
• Hungary
  • Budapest, Hungary, H-1121
    • K o ran y i National Institute of Pulmo nol ogy, 6th D epartm ent of Pulmono logy
  • Debrecen, Hungary, H-4032
    • University o f D ebrecen C linical Center, Department of Pulmono log y
  • Farkasgyepű, Hungary, 1-1-8582
    • Veszprem C ounty Pulmonology I nstitute
  • Pécs, Hungary, H-7623
    • Clinical Center of the University of Pecs, Depaitment ofPulmonology
  • Szekesfehervar, Hungary, H-8000
    • Fejer County St. Gyorgy University Teaching Hospital, Pulmonology Department I
  • Szolnok, Hungary, H-5000
    • Jasz-N agy kun-Szo l nok County H eteny i G eza 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 Oncoematology 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 Regiona l 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 K ragujevac
• 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
• Genders Eligible for Study: All

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 will be checked at screening visit (Visit 1).

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 or 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 will be checked at screening visit (Visit 1).

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
Placebo Comparator: placebo	Drug: Placebo Oral Tablet; Placebo (administered as matching placebo tablets in the fasted condition)
Experimental: 100mg Anamorelin HCl	Drug: Anamorelin Hydrochloride; 100 mg anamorelin HCl (administered as 100 mg tablets in the fasted condition)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
body weight	Mean change in body weight	From baseline until week 12
5 item Anorexia Symptom Subscale	Mean change in 5-item Anorexia Symptom Subscale	From baseline until week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
body weight	Duration of treatment benefit in weight (≥0).	From baseline until week 12
body weight	Duration of treatment benefit in weight (≥ to a predefined threshold).	From baseline until week 12
5 item Anorexia Symptom Subscale	Duration of treatment benefit in anorexia symptoms (≥0), as measured by the 5-item Anorexia Symptom Subscale.	From baseline until week 12
5 item Anorexia Symptom Subscale	Duration of treatment benefit in 5-item Anorexia Symptom Subscale (≥ to a predefined threshold).	From baseline until week 12
FAACT 12-item A/CS domain	Mean change in FAACT 12-item A/CS domain.	From baseline until week 12
FACIT-F	Mean change in FACIT-F.	From baseline until week 12
FAACT total score	Mean change in FAACT total score.	From baseline until week 12

Collaborators and Investigators

• Sponsor: Helsinn Healthcare SA

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2018
• Primary Completion (Actual): August 12, 2022
• Study Completion (Actual): February 13, 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): April 6, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

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; Emaciation; 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