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)

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.

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Actual): 318
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia, 5042
    • Flinders Medical Centre
  • Fitzroy, Australia, 3065
    • St Vincent's Hospital Melbourne
  • North Geelong, Australia, 3215
    • Barwon Health, The McKellar Centre
  • Parkville, Australia, 3050
    • The Royal Melbourne Hospital
  • Southport, Australia, 4215
    • Gold Coast University Hospital
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 5112
      • Calvary Central Districts Hospital
• Belgium
  • Brussels, Belgium, 1200
    • Saint Luc University Hospital
  • Brussels, Belgium, 1000
    • Jules Bordet Institut
  • Charleroi, Belgium, 6000
    • Charleroi Grand Hospital (GHDC)
  • Edegem, Belgium, 2650
    • University Hospital Antwerp (UZA)
  • Roeselare, Belgium, 8800
    • General Hospital Delta
• Croatia
  • Pula, Croatia, 52 100
    • General Hospital Pula
  • Split, Croatia, 21000
    • University Hospital Center Split
  • Zagreb, Croatia, 10000
    • University Hospital Center Zagreb
• Poland
  • Grudziądz, Poland, 86-300
    • Wladyslaw Bieganski Regional Specialist Hospital, Clinical Oncology Department
  • Katowice, Poland, 40-060
    • "VEGAMED" Non-Public Healthcare Facility
  • Poznań, Poland, 60-693
    • MED - POLONIA Ltd.
  • Prabuty, Poland, 82-550
    • Specialist Hospital in Prabuty sp. z o.o. [limited liability company], Department of Pulmonology
  • Warsaw, Poland, 02-781
    • Maria Skfodowska-Curie Institute of Oncology, Department of Lung and Thoracic Cancers
  • Wieliszew, Poland, 05-135
    • Mazovian Oncology Hospital, Oncology Outpatient Clinic
  • Łódź, Poland, 90-302
    • MSF Institute Ltd. Santa Familia Medical Institute
• Romania
  • Bucharest, Romania, 022328
    • Alexandru Trestioreanu Institute of Oncology
  • Cluj County
    • Cluj-Napoca, Cluj County, Romania, 400015
      • "Prof. Dr. Ion Chiricuta" Institute of Oncology, Medical Oncology Department
  • Dolj County
    • Craiova, Dolj County, Romania, 200347
      • "Sf. Nectarie" Oncology Center, Medical Oncology Department
  • Maramures
    • Baia Mare, Maramures, Romania, 430291
      • SC Oncopremium Team SRL, Medical Oncology Department
  • Murers
    • Târgu-Mureş, Murers, Romania, 540156
      • Topmed Medical Center, Medical Oncology Department
  • Suceava County
    • Suceava, Suceava County, Romania, 720237
      • Sf. Ioan cel Nou Country Emergency Hospital, Oncology Department
  • Timis
    • Timisoara, Timis, Romania, 300239
      • S.C. Oncomed SRL, Medical Oncology Department
• Russian Federation
  • Kazan, Russian Federation, 420029
    • Republican Clinical Oncology Center
  • Pyatigorsk, Russian Federation, 357502
    • Pyatigorsk Interdistric Oncology Center
  • Saint Petersburg, Russian Federation, 196247
    • Oncology Center of Moskovskiy District
  • Saint Petersburg, Russian Federation, 197082
    • AV Medical Group
  • Saint Petersburg, Russian Federation, 198255
    • City Clinical Oncology Center
  • Samara, Russian Federation, 443031
    • Samara Regional Clinical Oncology Center
  • Saransk, Russian Federation, 430032
    • Ogaryov Mordovia National Research State University, Republican Oncology Center
  • Sochi, Russian Federation, 354057
    • Oncology Center #2
  • St. Petersburg, Russian Federation, 197183
    • Palliative Care Center Devita
  • Volgograd, Russian Federation, 400138
    • Volgograd Regional Clinical Oncology Center
• Ukraine
  • Dnipro, Ukraine, 49055
    • Medical Center "MEDICAL PLAZA" of the Limited Liability Company "EKODNIPRO"
  • Kyiv, Ukraine, 03037
    • Private Enterprise "First Private Clinic"
  • Ternopil', Ukraine, 46023
    • Public Non-Profit Enterprise 'Ternopil Regional Clinical Oncology Center'' under Temopil Regional Council
  • Zaporizhzhya, Ukraine, 69059
    • Medical Center of Limited Liability Company "ONCOLIFE"
  • Kharkiev
    • Kharkiv, Kharkiev, Ukraine, 61070
      • Communal Non-Profit Enterprise "Regional Center of Oncology"
  • Kharkiev Region
    • Kharkiv, Kharkiev Region, Ukraine, 61166
      • Publ Non- Profit Ent. under Kharkiv Reg. Council
  • Kyviv
    • Kyiv, Kyviv, Ukraine, 3039
      • Medical Center "VERUM" Limited Liability Company
  • Poltava Region
    • Poltava, Poltava Region, Ukraine, 36011
      • Public Entreprise "Poltava Regional Clinical Oncology Center under Poltava Regional Council"
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • The University of Arizona Cancer Center - North Campus
  • California
    • Anaheim, California, United States, 92801
      • Pacific Cancer Medical Center, Inc
    • Bakersfield, California, United States, 93309
      • CBCC Global Research Inc
    • Fountain Valley, California, United States, 92708
      • Compassionate Care Research Group, Inc., at Compassionate Cancer Care Medical Group, Inc.
    • Greenbrae, California, United States, 94904
      • Marin Cancer Care
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Smilow Cancer Hospital at Yale-New Haven
  • Florida
    • Winter Haven, Florida, United States, 33881
      • Bond & Steele Clinic P.A.
  • Illinois
    • Skokie, Illinois, United States, 60077
      • Presence Infusion Care
  • Iowa
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center dba June E.Nylen Cancer Center
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Cancer and Hematology Centers of Western Michigan
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • New Jersey Hematology Oncology Associates Inc
    • Flemington, New Jersey, United States, 08822
      • Hunterdon Hematology Oncology LLC
  • New York
    • Nyack, New York, United States, 10960
      • Hematology Oncology Center at Nyack Hospital
    • Rochester, New York, United States, 14642
      • University of Rochester, Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center
  • Ohio
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cancer Center-Toledo
  • Texas
    • Houston, Texas, United States, 77030-4009
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

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
Experimental: 100 mg 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	Drug: anamorelin HCl; 100 mg anamorelin HCl (administered as 100 mg tablets in the fasted condition)
Placebo Comparator: Placebo; Placebo (administered as matching placebo tablets in fasted condition) was to be taken orally once daily for a total of 24 weeks	Drug: Placebo Oral Tablet; Placebo (administered as matching placebo tablets in the fasted condition)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Body Weight 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 over 12 weeks.
Mean Change From Baseline in 5-item Anorexia Symptom Subscale (5-IASS) 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 over 12 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration in Treatment Benefit (Weeks) From Baseline Over 12 Weeks in Body Weight (≥0 kg)	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 from baseline over 12 weeks.
Duration in Treatment Benefit (Weeks) From Baseline Over 12 Weeks in Body Weight (≥1.5 kg)	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 from baseline over 12 weeks.
Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in 5-IASS (≥0 Points)	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 of treatment benefit from baseline over 12 weeks.
Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in 5-IASS (≥3 Points)	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 from baseline over 12 weeks.

Collaborators and Investigators

• Sponsor: Helsinn Healthcare SA

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2019
• Primary Completion (Actual): December 27, 2022
• Study Completion (Actual): December 27, 2022

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): June 26, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

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; Thinness; Anorexia; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Weight Loss; Cachexia
• Other Study ID Numbers: ANAM-17-21; 2018-002927-40 (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