Clinical trial NCT03743051: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cachexia; Cancer
Non Small Cell Lung Cancer
Lead sponsor: Helsinn Healthcare SA
Sponsor class: INDUSTRY
First posted: 2018-11-15
Enrollment: 318
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind, Placebo-Controlled, Multicenter Study
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Mean Change From Baseline in Body Weight Over 12 Weeks
timeFrame: Mean change from baseline over 12 weeks.
measure: Mean Change From Baseline in 5-item Anorexia Symptom Subscale (5-IASS) Over 12 Weeks
timeFrame: Mean change from baseline over 12 weeks.
Secondary outcomes:
measure: Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in Body Weight (≥0 kg)
timeFrame: Duration of treatment benefit from baseline over 12 weeks.
measure: Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in Body Weight (≥1.5 kg)
timeFrame: Duration of treatment benefit from baseline over 12 weeks.
measure: Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in 5-IASS (≥0 Points)
timeFrame: Duration of treatment benefit from baseline over 12 weeks.
measure: Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in 5-IASS (≥3 Points)
timeFrame: Duration of treatment benefit from baseline over 12 weeks.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Chen
state: Arizona
city: Little Rock
country: United States
facility: CARTI Cancer Center
state: Arkansas
city: Riverside
country: United States
facility: The Oncology Insitute of Hope and Innovation
state: California
city: Plainville
country: United States
facility: Hartford HealthCare Cancer Institute at the Hospital of Central Connecticut
state: Connecticut
city: Jacksonville
country: United States
facility: 21st Century Oncology
state: Florida
city: Orange City
country: United States
facility: Mid Florida Hematology and Oncology Center
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology Hematology Associates, Ltd
state: Illinois
city: Goshen
country: United States
facility: Goshen Center for Cancer Care
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Waterloo
country: United States
facility: MercyOne Waterloo Cancer Center
state: Iowa
city: Jackson
country: United States
facility: Jackson Oncology Associates, PLC
state: Minnesota
city: Elizabeth
country: United States
facility: Trinitas Comprehensive Cancer Center/Trinitas Regional Medical Center
state: New Jersey
city: Englewood
country: United States
facility: Englewood Health
state: New Jersey
city: Johnson City
country: United States
facility: Broome Oncology LLC
state: New York
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Cancer Center
state: New York
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center The James Cancer Hospital and Solove Research Institute
state: Ohio
city: Gettysburg
country: United States
facility: Gettysburg Cancer Center
state: Pennsylvania
city: Knoxville
country: United States
facility: Tennessee Cancer Specialist
state: Tennessee
city: Ogden
country: United States
facility: Community Cancer Trial of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University, Massey Cancer Center
state: Virginia
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Hospital & Clinics
state: Washington
city: Burgas
country: Bulgaria
facility: Department of Medical Oncology, Complex Oncology Center - Burgas, Burgas
city: Dobrich
country: Bulgaria
facility: Department of Medical Oncology, Multiprofile Hospital for Active Treatment - Dobrich, Dobrich
city: Gabrovo
country: Bulgaria
facility: Department of Medical Oncology, Multiprofile Hospital for Active Treatment
city: Sofia
country: Bulgaria
facility: Department of Medical Oncology, Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda, Sofia
city: Varna
country: Bulgaria
facility: Clinic of Medical Oncology, Hospital Sveta Marina
city: Varna
country: Bulgaria
facility: Clinic on Medical Oncology University Multiprofile Hospital for Active Treatment "Sveta Marina", Varna
city: Budapest
country: Hungary
facility: Koranyi National Institute of Pulmonology, 6th Department of Pulmonology
city: Debrecen
country: Hungary
facility: University of Debrecen Clinical Center, Department of Pulmonology
city: Farkasgyepű
country: Hungary
facility: Veszprem County Pulmonology Institute
city: Pécs
country: Hungary
facility: Clinical Center of the University of Pecs, Department of Pulmonology
city: Szekesfehervar
country: Hungary
facility: Fejer County St. Gyorgy University Teaching Hospital, Pulmonology Department I
city: Szolnok
country: Hungary
facility: Jasz-Nagy Kun-Szolnok County Hetenyi Geza Hospital-Clinic, Department of Oncology
city: Törökbálint
country: Hungary
facility: Pulmonology Institute Torokbalint
city: Cona
country: Italy
facility: University Hospital of Ferrara, Oncology Department
state: Ferrara
city: Meldola
country: Italy
facility: Scientific Institute of Romagna for the Study and Treatment of Cancer (IRST)
state: Forli
city: Legnago
country: Italy
facility: Hospital Mater Salutis
state: Italia
city: Lido Di Camaiore
country: Italy
facility: Versilia Hospital
state: Italia
city: Piacenza
country: Italy
facility: Hospital "Guglielmo da Saliceto"
state: Italia
city: Aviano
country: Italy
facility: Oncology Reference Center
city: Monza
country: Italy
facility: Local Healthcare Company of Monza (ASST Monza)
city: Napoli
country: Italy
facility: AOU University Luigi Vanvitelli Oncohematology Department
city: Roma
country: Italy
facility: Umberto I Policlinico la Sapienza, Translational and Precision Medicine Department
city: Rom
country: Italy
facility: University Policlinic Fondation Agostino Gemelli
city: Oradea
country: Romania
facility: S.C. Pelican Impex S.R.L
state: Bihor
city: Cluj Napoca
country: Romania
facility: Medisprof S.R.L
state: Cluj
city: Craiova
country: Romania
facility: S.C. Onco Clinic Consult SA
state: Dolj
city: Targu Mures
country: Romania
facility: Mures County Clinical Hospital
state: Mures
city: Ploiesti
country: Romania
facility: Ploiesti Municipal Hospital
state: Prahova
city: Timisoara
country: Romania
facility: Oncocenter - Oncologie Clinica SRL
state: Timis
city: Obninsk
country: Russian Federation
facility: National Medical Research Radiological Centre (Tsyb Medical Radiology Research Center)
state: Kaluga Region
city: Chelyabinsk
country: Russian Federation
facility: Evimed, LLC
city: Ivanovo
country: Russian Federation
facility: lvanovo Regional Oncology Center
city: Izhevsk
country: Russian Federation
facility: Primushko Republicun Clinical Oncology Center
city: Kaliningrad
country: Russian Federation
facility: Immanuel Kant Baltic Federal University
city: Kursk
country: Russian Federation
facility: Kursk Regional Clinical Oncology Center
city: Moscow
country: Russian Federation
facility: YitaMed, LLC
city: Moscow
country: Russian Federation
facility: University Headache Clinic
city: Omsk
country: Russian Federation
facility: Clinical Oncology Center
city: Omsk
country: Russian Federation
facility: Clinical Oncology Center
city: Saint Petersburg
country: Russian Federation
facility: First I.P. Pavlov State Medical University of St. Petersburg
city: Saint Petersburg
country: Russian Federation
facility: City Outpatient Clinic #43
city: Tambov
country: Russian Federation
facility: Tambov Regional Oncological Clinical Center
city: Tomsk
country: Russian Federation
facility: Tomsk National Research Medical Center
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia, Clinic of Pulmonology
city: Belgrade
country: Serbia
facility: Clinical Hospital Center l\emnijsJca kosa
city: Belgrade
country: Serbia
facility: Medical Military Academy
city: Belgrade
country: Serbia
facility: Oncomed-System, Specialized Hospital for Internal Diseases
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
Study officials:
References: