Clinical trial NCT03743064: 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 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 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).

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