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)

NCT ID: NCT03743064

Last Updated: 2024-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 318 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-06
• Study Completion Date: 2022-12-27

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.

Conditions

Cachexia; Cancer; Non Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

anamorelin HCl

Intervention Type: DRUG

100 mg anamorelin HCl (administered as 100 mg tablets in the fasted condition)

Placebo

Placebo (administered as matching placebo tablets in fasted condition) was to be taken orally once daily for a total of 24 weeks

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

Placebo (administered as matching placebo tablets in the fasted condition)

Interventions

anamorelin HCl

100 mg anamorelin HCl (administered as 100 mg tablets in the fasted condition)

Intervention Type: DRUG

Placebo Oral Tablet

Placebo (administered as matching placebo tablets in the fasted condition)

Intervention Type: DRUG

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.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Helsinn Healthcare SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The University of Arizona Cancer Center - North Campus

Tucson, Arizona, United States

Pacific Cancer Medical Center, Inc

Anaheim, California, United States

CBCC Global Research Inc

Bakersfield, California, United States

Compassionate Care Research Group, Inc., at Compassionate Cancer Care Medical Group, Inc.

Fountain Valley, California, United States

Marin Cancer Care

Greenbrae, California, United States

Smilow Cancer Hospital at Yale-New Haven

Waterbury, Connecticut, United States

Bond & Steele Clinic P.A.

Winter Haven, Florida, United States

Presence Infusion Care

Skokie, Illinois, United States

Siouxland Regional Cancer Center dba June E.Nylen Cancer Center

Sioux City, Iowa, United States

Cancer Center of Kansas

Wichita, Kansas, United States

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, United States

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

New Jersey Hematology Oncology Associates Inc

Brick, New Jersey, United States

Hunterdon Hematology Oncology LLC

Flemington, New Jersey, United States

Hematology Oncology Center at Nyack Hospital

Nyack, New York, United States

University of Rochester, Medical Center

Rochester, New York, United States

Duke Cancer Center

Durham, North Carolina, United States

Toledo Clinic Cancer Center-Toledo

Toledo, Ohio, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Calvary Central Districts Hospital

Elizabeth Vale, South Australia, Australia

Flinders Medical Centre

Bedford Park, , Australia

St Vincent's Hospital Melbourne

Fitzroy, , Australia

Barwon Health, The McKellar Centre

North Geelong, , Australia

The Royal Melbourne Hospital

Parkville, , 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 Antwerp (UZA)

Edegem, , Belgium

General Hospital Delta

Roeselare, , Belgium

General Hospital Pula

Pula, , Croatia

University Hospital Center Split

Split, , Croatia

University Hospital Center Zagreb

Zagreb, , Croatia

Wladyslaw Bieganski Regional Specialist Hospital, Clinical Oncology Department

Grudziądz, , Poland

"VEGAMED" Non-Public Healthcare Facility

Katowice, , Poland

MSF Institute Ltd. Santa Familia Medical Institute

Lodz, , Poland

MED - POLONIA Ltd.

Poznan, , Poland

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

Mazovian Oncology Hospital, Oncology Outpatient Clinic

Wieliszew, , Poland

"Prof. Dr. Ion Chiricuta" Institute of Oncology, Medical Oncology Department

Cluj-Napoca, Cluj, Romania

"Sf. Nectarie" Oncology Center, Medical Oncology Department

Craiova, Dolj, Romania

SC Oncopremium Team SRL, Medical Oncology Department

Baia Mare, Maramureş, Romania

Topmed Medical Center, Medical Oncology Department

Târgu Mureş, Murers, Romania

Sf. Ioan cel Nou Country Emergency Hospital, Oncology Department

Suceava, Suceava, Romania

S.C. Oncomed SRL, Medical Oncology Department

Timișoara, Timiș County, Romania

Alexandru Trestioreanu Institute of Oncology

Bucharest, , Romania

Republican Clinical Oncology Center

Kazan', , Russia

Pyatigorsk Interdistric Oncology Center

Pyatigorsk, , Russia

Oncology Center of Moskovskiy District

Saint Petersburg, , Russia

AV Medical Group

Saint Petersburg, , Russia

Palliative Care Center Devita

Saint Petersburg, , Russia

City Clinical Oncology Center

Saint Petersburg, , Russia

Samara Regional Clinical Oncology Center

Samara, , Russia

Ogaryov Mordovia National Research State University, Republican Oncology Center

Saransk, , Russia

Oncology Center #2

Sochi, , Russia

Volgograd Regional Clinical Oncology Center

Volgograd, , Russia

Publ Non- Profit Ent. under Kharkiv Reg. Council

Kharkiv, Kharkiev Region, Ukraine

Communal Non-Profit Enterprise "Regional Center of Oncology"

Kharkiv, Kharkiev, Ukraine

Medical Center "VERUM" Limited Liability Company

Kyiv, Kyviv, Ukraine

Public Entreprise "Poltava Regional Clinical Oncology Center under Poltava Regional Council"

Poltava, Poltava Oblast, Ukraine

Medical Center "MEDICAL PLAZA" of the Limited Liability Company "EKODNIPRO"

Dnipro, , Ukraine

Private Enterprise "First Private Clinic"

Kyiv, , Ukraine

Public Non-Profit Enterprise 'Ternopil Regional Clinical Oncology Center'' under Temopil Regional Council

Ternopil, , Ukraine

Medical Center of Limited Liability Company "ONCOLIFE"

Zaporizhzhya, , Ukraine

Countries

United States; Australia; Belgium; Croatia; Poland; Romania; Russia; Ukraine

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-002927-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ANAM-17-21

Identifier Type: -

Identifier Source: org_study_id