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: NCT03743051
• Other study ID #: ANAM-17-20
• Secondary ID: 2018-002926-22
• Status: Completed
• Phase: Phase 3
• Start date: December 18, 2018
• Est. completion date: February 13, 2023

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: 316
• Est. completion date: February 13, 2023
• Est. primary completion date: August 12, 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 Hydrochloride
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
Bulgaria	Department of Medical Oncology, Complex Oncology Center - Burgas, Burgas	Burgas
Bulgaria	Department of Medical Oncology, Multiprofile Hospital for Active Treatment- Dobrich, Dobrich	Dobrich
Bulgaria	Department of Medical Oncology, Multiprofile Hospital for Acti ve T reatment ··Dr. Tota Venkova" , Gabrovo	Gabrovo
Bulgaria	Department of Medical Oncology, Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda, Sofia	Sofia
Bulgaria	clinic of medical oncology,hospital Sveta marina	Varna
Bulgaria	Clinic on Medical oncology University Muliprofile Hospital for active treatment "Sveta Marina", Varna	Varna
Hungary	K o ran y i National Institute of Pulmo nol ogy, 6th D epartm ent of Pulmono logy	Budapest
Hungary	University o f D ebrecen C linical Center, Department of Pulmono log y	Debrecen
Hungary	Veszprem C ounty Pulmonology I nstitute	Farkasgyepu
Hungary	Clinical Center of the University of Pecs, Depaitment ofPulmonology	Pécs
Hungary	Fejer County St. Gyorgy University Teaching Hospital, Pulmonology Department I	Szekesfehervar
Hungary	Jasz-N agy kun-Szo l nok County H eteny i G eza Hospital-Clinic, Department of Oncology	Szolnok
Hungary	Pulmonology Institute Torokbalint	Törökbálint
Italy	Oncology reference center	Aviano
Italy	University Hospital of Ferrara, Oncology department	Cona	Ferrara
Italy	Hospital Mater Salutis	Legnago	Italia
Italy	Versilia Hospital	Lido Di Camaiore	Italia
Italy	Scientific Institute of Romagna for the study and treatment of cancer (IRST)	Meldola	Forli
Italy	Local Healthcare Company of Monza (ASST Monza)	Monza
Italy	AOU University Luigi Vanvitelli Oncoematology department	Napoli
Italy	Hospital "Guglielmo da Saliceto"	Piacenza	Italia
Italy	University Policlinic Fondation Agostino Gemelli	Rom
Italy	Umberto I policlinico la Sapienza, Translational and Precision Medicine department	Roma
Romania	Medisprof S.R.L	Cluj Napoca	Cluj
Romania	S.C. Onco Clinic Consult SA	Craiova	Dolj
Romania	S.C. Pelican Impex S.R.L	Oradea	Bihor
Romania	Ploiesti Municipal Hospital	Ploiesti	Prahova
Romania	Mures County Clinical Hospital	Targu Mures	Mures
Romania	Oncocenter - Oncologie Clinica SRL	Timisoara	Timis
Russian Federation	Evimed, LLC	Chelyabinsk
Russian Federation	lvanovo Regional Oncology Center	Ivanovo
Russian Federation	Primushko Republicun Clinical Oncology Center	Izhevsk
Russian Federation	Immanuel Kant Baltic Federal University	Kaliningrad
Russian Federation	Kursk Regiona l Clinical Oncology Center	Kursk
Russian Federation	University Headache Clinic	Moscow
Russian Federation	YitaMed, LLC	Moscow
Russian Federation	National Medical Research Radiological Centre (Tsyb Medical Radiology Research Center)	Obninsk	Kaluga Region
Russian Federation	Clinical Oncology Center	Omsk
Russian Federation	Clinical Oncology Center	Omsk
Russian Federation	City Outpatient Clinic #43	Saint Petersburg
Russian Federation	First I.P. Pavlov State Medical University of St. Petersburg	Saint Petersburg
Russian Federation	Tambov Regional Oncological Clinical Center	Tambov
Russian Federation	Tomsk National Research Medical Center	Tomsk
Serbia	Clinical Center of Serbia, Clinic of Pulmonology	Belgrade
Serbia	Clinical Hospital Center l\emnijsJca kosa	Belgrade
Serbia	Medical Military Academy	Belgrade
Serbia	Oncomed-System, Specialized Hospital for Internal Diseases	Belgrade
Serbia	Clinical Center K ragujevac	Kragujevac
United States	McFarland Clinic, PC	Ames	Iowa
United States	Rush University Medical Center	Chicago	Illinois
United States	Ohio State University Wexner Medical Center The James Cancer Hospital and Solove Research Institute	Columbus	Ohio
United States	trinitas comprehensive cancer center/Trinitas Regional Medical Center	Elizabeth	New Jersey
United States	Englewood Health	Englewood	New Jersey
United States	Gettysburg Cancer Center	Gettysburg	Pennsylvania
United States	Goshen Center for Cancer Care	Goshen	Indiana
United States	Jackson oncology Associates, PLC	Jackson	Minnesota
United States	21st Century oncology	Jacksonville	Florida
United States	Broome Oncology LLC	Johnson City	New York
United States	Joliet Oncology hematology Associates, Ltd	Joliet	Illinois
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Tennessee Cancer Specialist	Knoxville	Tennessee
United States	Northwell Health	Lake Success	New York
United States	CARTI Cancer center	Little Rock	Arkansas
United States	Community Cancer Trial of Utah	Ogden	Utah
United States	mid Florida hematology and Oncology Center	Orange City	Florida
United States	Hartford HealthCare Cancer Institute at The Hospital of Central Connecticut	Plainville	Connecticut
United States	Virginia Commonwealth University, Massey Cancer Center	Richmond	Virginia
United States	the oncology Insitute of Hope and Innovation	Riverside	California
United States	Stony Brook Cancer Center	Stony Brook	New York
United States	Chen	Tucson	Arizona
United States	MercyOne Waterloo Cancer Center	Waterloo	Iowa
United States	Wenatchee Valley Hospital & Clinics	Wenatchee	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Helsinn Healthcare SA

Countries where clinical trial is conducted

United States,  Bulgaria,  Hungary,  Italy,  Romania,  Russian Federation,  Serbia, 

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