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)

Non Small Cell Lung Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03743064
• Other study ID #: ANAM-17-21
• Secondary ID: 2018-002927-40
• Status: Completed
• Phase: Phase 3
• Start date: December 18, 2018
• Est. completion date: December 23, 2022

Study information

• Verified date: April 2023
• Source: Helsinn Healthcare SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Multicenter, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy and safety of anamorelin HCl. Approximately 316 patients with advanced NSCLC with cachexia will be randomized 1:1 to anamorelin HCl 100 mg or placebo, taken orally once daily (QD) for a total of 24 weeks. Patients will be instructed to take the study drug at least 1 hour before their first meal of the day

Recruitment information / eligibility

• Status: Completed
• Enrollment: 318
• Est. completion date: December 23, 2022
• Est. primary completion date: July 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Anorexia
• Cachexia
• Cachexia; Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer
• Weight Loss

Intervention

Drug:
• anamorelin HCl
100 mg anamorelin HCl (administered as 100 mg tablets in the fasted condition)
• Placebo Oral Tablet
Placebo (administered as matching placebo tablets in the fasted condition)

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park
Australia	Calvary Central Districts Hospital	Elizabeth Vale	South Australia
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
Belgium	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
Croatia	General Hospital Pula	Pula
Croatia	University Hospital Center Split	Split
Croatia	University Hospital Center Zagreb	Zagreb
Poland	Wladyslaw Bieganski Regional Specialist Hospital, Clnical Oncology Department	Grudziadz
Poland	"VEGAMED" Non-Public Healthcare Facility	Katowice
Poland	MSF Institute Ltd. Santa Familia Medical Institute	Lódz
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
Romania	SC Oncopremium team SRL, Medical oncology department	Baia Mare	Maramures
Romania	Alexandru Trestioreanu Institute of Oncology	Bucharest
Romania	"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	Sf. Ioan cel Nou Country Emergency Hospital, Oncology department	Suceava	Suceava County
Romania	Topmed Medical center, Medical Oncology Department	Târgu-Mures	Murers
Romania	S.C. Oncomed SRL, Medical Oncology Department	Timisoara	Timis
Russian Federation	Republican Clinical Oncology Center	Kazan
Russian Federation	Pyatigorsk Interdistric Oncology Center	Pyatigorsk
Russian Federation	AV Medical Group	Saint Petersburg
Russian Federation	City Clinical Oncology Center	Saint Petersburg
Russian Federation	Oncology Center of Moskovskiy District	Saint Petersburg
Russian Federation	Samara Regional clinical Oncology Center	Samara
Russian Federation	Ogaryov Mordovia National Research State University, Republican Oncology Center	Saransk
Russian Federation	Oncology Center #2	Sochi
Russian Federation	Palliative Care Center Devita	St. Petersburg
Russian Federation	Volgograd Regional Clinical Oncology Center	Volgograd
Ukraine	Medical Center "MEDICAL PLAZA" of the Limited Liability Company "EKODNIPRO"	Dnipro
Ukraine	Communal Non-Profit Enterprise "Regional Center of Oncology"	Kharkiv	Kharkiev
Ukraine	Publ Non- Profit Ent. under Kharkiv Reg. Council	Kharkiv	Kharkiev Region
Ukraine	Medical Center "VERUM" Limited Liability Company	Kyiv	Kyviv
Ukraine	Private Enterprise "First Private Clinic"	Kyiv
Ukraine	Public Entreprise "Poltava Regional Clinical oncology Center under Poltava Regional Council"	Poltava	Poltava Region
Ukraine	Public Non-Profit Enterprise 'Ternopil Regional Clini cal Oncology Center'' under Temopil Regional Counci l	Ternopil'
Ukraine	Medical Center of Limited Liability Company "ONCOLIFE"	Zaporizhzhya
United States	Pacific Cancer Medical Center, Inc	Anaheim	California
United States	CBCC Global Research Inc	Bakersfield	California
United States	New Jersey Hematology Oncology associates Inc	Brick	New Jersey
United States	Duke Cancer Center	Durham	North Carolina
United States	Hunterdon hematology Oncology LLC	Flemington	New Jersey
United States	Compassionate Care Research Group, Inc., at Compassionate Cancer Care Medical Group, Inc.	Fountain Valley	California
United States	Cancer and Hematology Centers Of Western Michigan	Grand Rapids	Michigan
United States	Marin cancer Care	Greenbrae	California
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Hematology Oncology Center at Nyack Hospital	Nyack	New York
United States	University of Rochester, Medical Center	Rochester	New York
United States	Siouxland Regional cancer Center dba June E.Nylen Cancer Center	Sioux City	Iowa
United States	Presence Infusion Care	Skokie	Illinois
United States	Toledo Clinic Cancer center-Toledo	Toledo	Ohio
United States	The university of Arizona Cancer Center - North Campus	Tucson	Arizona
United States	Smilow Cancer Hospital at Yale-New Haven	Waterbury	Connecticut
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Bond & Steele Clinic P.A.	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Helsinn Healthcare SA

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Croatia,  Poland,  Romania,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	body weight	Mean change in body weight	From baseline until week 12
Primary	5 item Anorexia Symptom Subscale	Mean change in 5-item Anorexia Symptom Subscale	From baseline until week 12
Secondary	body weight	Duration of treatment benefit in weight (=0).	From baseline until week 12
Secondary	body weight	Duration of treatment benefit in weight (= to a predefined threshold).	From baseline until week 12
Secondary	5 item Anorexia Symptom Subscale	Duration of treatment benefit in anorexia symptoms (=0), as measured by the 5-item Anorexia Symptom Subscale.	From baseline until week 12
Secondary	5 item Anorexia Symptom Subscale	Duration of treatment benefit in 5-item Anorexia Symptom Subscale (= to a predefined threshold).	From baseline until week 12
Secondary	FAACT 12-item A/CS domain	Mean change in FAACT 12-item A/CS domain.	From baseline until week 12
Secondary	FACIT-F	Mean change in FACIT-F.	From baseline until week 12
Secondary	FAACT total score	Mean change in FAACT total score.	From baseline until week 12