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)

Phase 3

Completed

Conditions: Non Small Cell Lung Cancer
Cachexia; Cancer

Interventions: Drug: anamorelin HCl
Drug: Placebo Oral Tablet

Registration Number: NCT03743064

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 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

Inclusion Criteria

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:
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
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:
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.
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

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:
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
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 or 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:
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
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)
Patient unable to readily swallow oral tablets
Patient with severe gastrointestinal disease (including esophagitis, gastritis, malabsorption)
Patient with history of gastrectomy
Patient with uncontrolled diabetes mellitus or unmonitored diabetes mellitus
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
Patient receiving strong CYP3A4 inhibitors within 14 days of randomization
Patient currently receiving tube feedings or parenteral nutrition (either total or partial).
Current excessive alcohol or illicit drug use
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
Enrollment in a previous study with anamorelin HCl
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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
100 mg anamorelin HCl	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
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 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.
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.

Secondary Outcome Measures

Name	Time	Method
Duration in 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.
Duration in 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.

Trial Locations

Locations (65): The University of Arizona Cancer Center - North Campus
🇺🇸
Tucson, Arizona, United States
Cancer and Hematology Centers of Western Michigan
🇺🇸
Grand Rapids, Michigan, United States
New Jersey Hematology Oncology Associates Inc
🇺🇸
Brick, New Jersey, United States
Hunterdon Hematology Oncology LLC
🇺🇸
Flemington, New Jersey, United States
The Royal Melbourne Hospital
🇦🇺
Parkville, Australia
University Hospital Antwerp (UZA)
🇧🇪
Edegem, Belgium
General Hospital Delta
🇧🇪
Roeselare, Belgium
General Hospital Pula
🇭🇷
Pula, Croatia
Specialist Hospital in Prabuty sp. z o.o. [limited liability company], Department of Pulmonology
🇵🇱
Prabuty, Poland
Maria Skfodowska-Curie Institute of Oncology, Department of Lung and Thoracic Cancers
🇵🇱
Warsaw, Poland
Publ Non- Profit Ent. under Kharkiv Reg. Council
🇺🇦
Kharkiv, Kharkiev Region, Ukraine
"VEGAMED" Non-Public Healthcare Facility
🇵🇱
Katowice, Poland
Mazovian Oncology Hospital, Oncology Outpatient Clinic
🇵🇱
Wieliszew, Poland
Alexandru Trestioreanu Institute of Oncology
🇷🇴
Bucharest, Romania
AV Medical Group
🇷🇺
Saint Petersburg, Russian Federation
Cancer Center of Kansas
🇺🇸
Wichita, Kansas, United States
Pacific Cancer Medical Center, Inc
🇺🇸
Anaheim, California, United States
CBCC Global Research Inc
🇺🇸
Bakersfield, California, United States
Bond & Steele Clinic P.A.
🇺🇸
Winter Haven, Florida, United States
Smilow Cancer Hospital at Yale-New Haven
🇺🇸
Waterbury, Connecticut, United States
Marin Cancer Care
🇺🇸
Greenbrae, California, United States
Presence Infusion Care
🇺🇸
Skokie, Illinois, United States
Siouxland Regional Cancer Center dba June E.Nylen Cancer Center
🇺🇸
Sioux City, Iowa, United States
Hematology Oncology Center at Nyack Hospital
🇺🇸
Nyack, New York, United States
The University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Duke Cancer Center
🇺🇸
Durham, North Carolina, United States
Calvary Central Districts Hospital
🇦🇺
Elizabeth Vale, South Australia, Australia
Toledo Clinic Cancer Center-Toledo
🇺🇸
Toledo, Ohio, United States
Flinders Medical Centre
🇦🇺
Bedford Park, Australia
Barwon Health, The McKellar Centre
🇦🇺
North Geelong, Australia
St Vincent's Hospital Melbourne
🇦🇺
Fitzroy, Australia
Gold Coast University Hospital
🇦🇺
Southport, Australia
Jules Bordet Institut
🇧🇪
Brussels, Belgium
Saint Luc University Hospital
🇧🇪
Brussels, Belgium
Charleroi Grand Hospital (GHDC)
🇧🇪
Charleroi, Belgium
University Hospital Center Split
🇭🇷
Split, Croatia
University Hospital Center Zagreb
🇭🇷
Zagreb, Croatia
Wladyslaw Bieganski Regional Specialist Hospital, Clinical Oncology Department
🇵🇱
Grudziądz, Poland
MED - POLONIA Ltd.
🇵🇱
Poznań, Poland
MSF Institute Ltd. Santa Familia Medical Institute
🇵🇱
Łódź, Poland
"Prof. Dr. Ion Chiricuta" Institute of Oncology, Medical Oncology Department
🇷🇴
Cluj-Napoca, Cluj County, Romania
"Sf. Nectarie" Oncology Center, Medical Oncology Department
🇷🇴
Craiova, Dolj County, Romania
Topmed Medical Center, Medical Oncology Department
🇷🇴
Târgu-Mureş, Murers, Romania
SC Oncopremium Team SRL, Medical Oncology Department
🇷🇴
Baia Mare, Maramures, Romania
S.C. Oncomed SRL, Medical Oncology Department
🇷🇴
Timisoara, Timis, Romania
Sf. Ioan cel Nou Country Emergency Hospital, Oncology Department
🇷🇴
Suceava, Suceava County, Romania
Pyatigorsk Interdistric Oncology Center
🇷🇺
Pyatigorsk, Russian Federation
Oncology Center of Moskovskiy District
🇷🇺
Saint Petersburg, Russian Federation
Republican Clinical Oncology Center
🇷🇺
Kazan, Russian Federation
Samara Regional Clinical Oncology Center
🇷🇺
Samara, Russian Federation
City Clinical Oncology Center
🇷🇺
Saint Petersburg, Russian Federation
Palliative Care Center Devita
🇷🇺
St. Petersburg, Russian Federation
Ogaryov Mordovia National Research State University, Republican Oncology Center
🇷🇺
Saransk, Russian Federation
Oncology Center #2
🇷🇺
Sochi, Russian Federation
Volgograd Regional Clinical Oncology Center
🇷🇺
Volgograd, Russian Federation
Communal Non-Profit Enterprise "Regional Center of Oncology"
🇺🇦
Kharkiv, Kharkiev, Ukraine
Medical Center "VERUM" Limited Liability Company
🇺🇦
Kyiv, Kyviv, Ukraine
Medical Center "MEDICAL PLAZA" of the Limited Liability Company "EKODNIPRO"
🇺🇦
Dnipro, Ukraine
Public Entreprise "Poltava Regional Clinical Oncology Center under Poltava Regional Council"
🇺🇦
Poltava, Poltava Region, Ukraine
Medical Center of Limited Liability Company "ONCOLIFE"
🇺🇦
Zaporizhzhya, Ukraine
Private Enterprise "First Private Clinic"
🇺🇦
Kyiv, Ukraine
Public Non-Profit Enterprise 'Ternopil Regional Clinical Oncology Center'' under Temopil Regional Council
🇺🇦
Ternopil', Ukraine
Compassionate Care Research Group, Inc., at Compassionate Cancer Care Medical Group, Inc.
🇺🇸
Fountain Valley, California, United States
Dartmouth-Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
University of Rochester, Medical Center
🇺🇸
Rochester, New York, United States