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)
- Conditions
- Cachexia; CancerNon Small Cell Lung Cancer
- Interventions
- Drug: Placebo Oral Tablet
- Registration Number
- NCT03743051
- Lead Sponsor
- Helsinn Healthcare SA
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 318
-
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
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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
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AST (SGOT) and ALT (SGPT) ≤ 3 x ULN or if hepatic metastases are present ≤ 5 x ULN
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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:
- 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.
- Reliable contraceptive measures include implants, injectables, combined oral contraceptives, intrauterine devices, vasectomized partner or complete (long term) sexual abstinence.
-
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).
-
Patient with other forms of lung cancer (e.g., small cell, neuroendocrine tumors)
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Woman who is pregnant or breast-feeding
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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
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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
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, Wolff-Parkinson-White (WPW) syndrome, or torsade de pointes)
- Uncontrolled hypertension (blood pressure >150 mm Hg systolic and >95 mm Hg diastolic)
- Heart rate < 50 beats per minute on pre-entry electrocardiogram and patient is symptomatic
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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)
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Patient unable to readily swallow oral tablets
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Patient with severe gastrointestinal disease (including esophagitis, gastritis, malabsorption)
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Patient with history of gastrectomy
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Patient with uncontrolled diabetes mellitus or unmonitored diabetes mellitus
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Patient with cachexia caused by other reasons, as determined by the investigator such as:
- Severe COPD requiring use of home O2,
- New York Heart Association (NYHA) class III-IV heart failure
- AIDS
- Uncontrolled thyroid disease
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Patient receiving strong CYP3A4 inhibitors within 14 days of randomization
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Patient currently receiving tube feedings or parenteral nutrition (either total or partial).
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Current excessive alcohol or illicit drug use
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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
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Enrollment in a previous study with anamorelin HCl
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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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 100 mg anamorelin HCl Anamorelin Hydrochloride 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 placebo Placebo Oral Tablet Placebo (administered as matching placebo tablets in fasted condition) was to be taken orally once daily for a total of 24 weeks
- Primary Outcome Measures
Name Time Method Mean Change From Baseline in 5-item Anorexia Symptom Subscale (5-IASS) Over 12 Weeks Mean change from baseline 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 in Body Weight Over 12 Weeks Mean change from baseline 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.
- Secondary Outcome Measures
Name Time Method 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. 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 (Weeks) From Baseline Over 12 Weeks in 5-IASS (≥3 Points) Duration of treatment benefit from baseline over 12 weeks. 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 (Weeks) From Baseline Over 12 Weeks in Body Weight (≥0 kg) Duration of treatment benefit from baseline over 12 weeks. 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 (Weeks) From Baseline Over 12 Weeks in 5-IASS (≥0 Points) Duration of treatment benefit from baseline over 12 weeks. 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.
Trial Locations
- Locations (71)
Englewood Health
🇺🇸Englewood, New Jersey, United States
Versilia Hospital
🇮🇹Lido Di Camaiore, Italia, Italy
S.C. Onco Clinic Consult SA
🇷🇴Craiova, Dolj, Romania
Oncocenter - Oncologie Clinica SRL
🇷🇴Timisoara, Timis, Romania
National Medical Research Radiological Centre (Tsyb Medical Radiology Research Center)
🇷🇺Obninsk, Kaluga Region, Russian Federation
Evimed, LLC
🇷🇺Chelyabinsk, Russian Federation
lvanovo Regional Oncology Center
🇷🇺Ivanovo, Russian Federation
City Outpatient Clinic #43
🇷🇺Saint Petersburg, Russian Federation
Tambov Regional Oncological Clinical Center
🇷🇺Tambov, Russian Federation
Tomsk National Research Medical Center
🇷🇺Tomsk, Russian Federation
Clinical Hospital Center l\emnijsJca kosa
🇷🇸Belgrade, Serbia
Clinical Center of Serbia, Clinic of Pulmonology
🇷🇸Belgrade, Serbia
Ohio State University Wexner Medical Center The James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
Wenatchee Valley Hospital & Clinics
🇺🇸Wenatchee, Washington, United States
Chen
🇺🇸Tucson, Arizona, United States
The Oncology Insitute of Hope and Innovation
🇺🇸Riverside, California, United States
Mid Florida Hematology and Oncology Center
🇺🇸Orange City, Florida, United States
McFarland Clinic, PC
🇺🇸Ames, Iowa, United States
MercyOne Waterloo Cancer Center
🇺🇸Waterloo, Iowa, United States
Trinitas Comprehensive Cancer Center/Trinitas Regional Medical Center
🇺🇸Elizabeth, New Jersey, United States
Jackson Oncology Associates, PLC
🇺🇸Jackson, Minnesota, United States
Broome Oncology LLC
🇺🇸Johnson City, New York, United States
Stony Brook Cancer Center
🇺🇸Stony Brook, New York, United States
Northwell Health
🇺🇸Lake Success, New York, United States
Community Cancer Trial of Utah
🇺🇸Ogden, Utah, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
Department of Medical Oncology, Complex Oncology Center - Burgas, Burgas
🇧🇬Burgas, Bulgaria
Department of Medical Oncology, Multiprofile Hospital for Active Treatment
🇧🇬Gabrovo, Bulgaria
Department of Medical Oncology, Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda, Sofia
🇧🇬Sofia, Bulgaria
Koranyi National Institute of Pulmonology, 6th Department of Pulmonology
🇭🇺Budapest, Hungary
University of Debrecen Clinical Center, Department of Pulmonology
🇭🇺Debrecen, Hungary
Clinical Center of the University of Pecs, Department of Pulmonology
🇭🇺Pécs, Hungary
Veszprem County Pulmonology Institute
🇭🇺Farkasgyepű, Hungary
Jasz-Nagy Kun-Szolnok County Hetenyi Geza Hospital-Clinic, Department of Oncology
🇭🇺Szolnok, Hungary
Pulmonology Institute Torokbalint
🇭🇺Törökbálint, Hungary
University Hospital of Ferrara, Oncology Department
🇮🇹Cona, Ferrara, Italy
Scientific Institute of Romagna for the Study and Treatment of Cancer (IRST)
🇮🇹Meldola, Forli, Italy
Hospital Mater Salutis
🇮🇹Legnago, Italia, Italy
Hospital "Guglielmo da Saliceto"
🇮🇹Piacenza, Italia, Italy
Local Healthcare Company of Monza (ASST Monza)
🇮🇹Monza, Italy
Oncology Reference Center
🇮🇹Aviano, Italy
AOU University Luigi Vanvitelli Oncohematology Department
🇮🇹Napoli, Italy
Umberto I Policlinico la Sapienza, Translational and Precision Medicine Department
🇮🇹Roma, Italy
University Policlinic Fondation Agostino Gemelli
🇮🇹Rom, Italy
S.C. Pelican Impex S.R.L
🇷🇴Oradea, Bihor, Romania
Medisprof S.R.L
🇷🇴Cluj Napoca, Cluj, Romania
Mures County Clinical Hospital
🇷🇴Targu Mures, Mures, Romania
Ploiesti Municipal Hospital
🇷🇴Ploiesti, Prahova, Romania
Immanuel Kant Baltic Federal University
🇷🇺Kaliningrad, Russian Federation
Kursk Regional Clinical Oncology Center
🇷🇺Kursk, Russian Federation
University Headache Clinic
🇷🇺Moscow, Russian Federation
First I.P. Pavlov State Medical University of St. Petersburg
🇷🇺Saint Petersburg, Russian Federation
Medical Military Academy
🇷🇸Belgrade, Serbia
Oncomed-System, Specialized Hospital for Internal Diseases
🇷🇸Belgrade, Serbia
Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Joliet Oncology Hematology Associates, Ltd
🇺🇸Joliet, Illinois, United States
Virginia Commonwealth University, Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Gettysburg Cancer Center
🇺🇸Gettysburg, Pennsylvania, United States
Clinic of Medical Oncology, Hospital Sveta Marina
🇧🇬Varna, Bulgaria
Goshen Center for Cancer Care
🇺🇸Goshen, Indiana, United States
Clinic on Medical Oncology University Multiprofile Hospital for Active Treatment "Sveta Marina", Varna
🇧🇬Varna, Bulgaria
YitaMed, LLC
🇷🇺Moscow, Russian Federation
CARTI Cancer Center
🇺🇸Little Rock, Arkansas, United States
Fejer County St. Gyorgy University Teaching Hospital, Pulmonology Department I
🇭🇺Szekesfehervar, Hungary
Hartford HealthCare Cancer Institute at the Hospital of Central Connecticut
🇺🇸Plainville, Connecticut, United States
Department of Medical Oncology, Multiprofile Hospital for Active Treatment - Dobrich, Dobrich
🇧🇬Dobrich, Bulgaria
Primushko Republicun Clinical Oncology Center
🇷🇺Izhevsk, Russian Federation
Clinical Oncology Center
🇷🇺Omsk, Russian Federation
Tennessee Cancer Specialist
🇺🇸Knoxville, Tennessee, United States
21st Century Oncology
🇺🇸Jacksonville, Florida, United States