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)

NCT03743064 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: ANAM-17-212018-002927-40
• Study Type: interventional
• Target: 318
• Locations: 8 countries
• Sites: 65

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.

Conditions

Cachexia; Cancer; Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Duration in Treatment Benefit (Weeks) From Baseline Over 12 Weeks in Body Weight (≥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)

  Duration of treatment benefit from baseline over 12 weeks.

• Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in 5-IASS (≥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)

  Duration of treatment benefit from baseline over 12 weeks.

Study Arms (2)

100 mg anamorelin HCl

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

anamorelin HCl DRUG

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

100 mg anamorelin HCl

Placebo Oral Tablet DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Female or male ≥18 years of age
• Documented histologic or cytologic diagnosis of American Joint Committee on Cancer (AJCC) Stage III or IV NSCLC. Stage III patient must have unresectable disease
• Body mass index \< 20 kg/m2 with involuntary weight loss of \>2% within 6 months prior to screening
• 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
• 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:
• 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
• 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
• Patient on palliative care treatment
• ECOG performance status 0,1 or 2 at screening
• AST (SGOT) and ALT (SGPT) ≤ 3 x ULN or if hepatic metastases are present ≤ 5 x ULN
• Adequate renal function, defined as creatinine ≤2 ULN, or calculated creatinine clearance \>30 ml/minute
• 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:

You may not qualify if:

• Patient with other forms of lung cancer (e.g., small cell, neuroendocrine tumors)
• Woman who is pregnant or breast-feeding
• Reversible causes of reduced food intake, as determined by the Investigator. These causes may include but are not limited to:
• NCI CTCAE Grade 3 or 4 oral mucositis,
• NCI CTCAE Grade 3 or 4 GI disorders \[nausea, vomiting, diarrhea, and constipation\],
• mechanical obstructions making patient unable to eat, or
• severe depression
• 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
• 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
• Patient with pleural effusion requiring thoracentesis, pericardial effusion requiring drainage, edema or evidence of ascites
• Patient with uncontrolled or significant cardiovascular disease, including:
• History of myocardial infarction within the past 3 months
• A-V block of second or third degree (may be eligible if currently have a pacemaker)
• Unstable angina
• Congestive heart failure within the past 3 months, if defined as NYHA class III-IV

Sponsors & Collaborators

• Helsinn Healthcare SA: lead

Study Sites (65)

The University of Arizona Cancer Center - North Campus

Tucson, Arizona, 85719, United States

Location

Pacific Cancer Medical Center, Inc

Anaheim, California, 92801, United States

Location

CBCC Global Research Inc

Bakersfield, California, 93309, United States

Location

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

Fountain Valley, California, 92708, United States

Location

Marin Cancer Care

Greenbrae, California, 94904, United States

Location

Smilow Cancer Hospital at Yale-New Haven

Waterbury, Connecticut, 06708, United States

Location

Bond & Steele Clinic P.A.

Winter Haven, Florida, 33881, United States

Location

Presence Infusion Care

Skokie, Illinois, 60077, United States

Location

Siouxland Regional Cancer Center dba June E.Nylen Cancer Center

Sioux City, Iowa, 51101, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, 49503, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

New Jersey Hematology Oncology Associates Inc

Brick, New Jersey, 08724, United States

Location

Hunterdon Hematology Oncology LLC

Flemington, New Jersey, 08822, United States

Location

Hematology Oncology Center at Nyack Hospital

Nyack, New York, 10960, United States

Location

University of Rochester, Medical Center

Rochester, New York, 14642, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Toledo Clinic Cancer Center-Toledo

Toledo, Ohio, 43623, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Calvary Central Districts Hospital

Elizabeth Vale, South Australia, 5112, Australia

Location

Flinders Medical Centre

Bedford Park, 5042, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, 3065, Australia

Location

Barwon Health, The McKellar Centre

North Geelong, 3215, Australia

Location

The Royal Melbourne Hospital

Parkville, 3050, Australia

Location

Gold Coast University Hospital

Southport, 4215, Australia

Location

Jules Bordet Institut

Brussels, 1000, Belgium

Location

Saint Luc University Hospital

Brussels, 1200, Belgium

Location

Charleroi Grand Hospital (GHDC)

Charleroi, 6000, Belgium

Location

University Hospital Antwerp (UZA)

Edegem, 2650, Belgium

Location

General Hospital Delta

Roeselare, 8800, Belgium

Location

General Hospital Pula

Pula, 52 100, Croatia

Location

University Hospital Center Split

Split, 21000, Croatia

Location

University Hospital Center Zagreb

Zagreb, 10000, Croatia

Location

Wladyslaw Bieganski Regional Specialist Hospital, Clinical Oncology Department

Grudziądz, 86-300, Poland

Location

"VEGAMED" Non-Public Healthcare Facility

Katowice, 40-060, Poland

Location

MSF Institute Ltd. Santa Familia Medical Institute

Lodz, 90-302, Poland

Location

MED - POLONIA Ltd.

Poznan, 60-693, Poland

Location

Specialist Hospital in Prabuty sp. z o.o. [limited liability company], Department of Pulmonology

Prabuty, 82-550, Poland

Location

Maria Skfodowska-Curie Institute of Oncology, Department of Lung and Thoracic Cancers

Warsaw, 02-781, Poland

Location

Mazovian Oncology Hospital, Oncology Outpatient Clinic

Wieliszew, 05-135, Poland

Location

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

Cluj-Napoca, Cluj, 400015, Romania

Location

"Sf. Nectarie" Oncology Center, Medical Oncology Department

Craiova, Dolj, 200347, Romania

Location

SC Oncopremium Team SRL, Medical Oncology Department

Baia Mare, Maramureş, 430291, Romania

Location

Topmed Medical Center, Medical Oncology Department

Târgu Mureş, Murers, 540156, Romania

Location

Sf. Ioan cel Nou Country Emergency Hospital, Oncology Department

Suceava, Suceava, 720237, Romania

Location

S.C. Oncomed SRL, Medical Oncology Department

Timișoara, Timiș County, 300239, Romania

Location

Alexandru Trestioreanu Institute of Oncology

Bucharest, 022328, Romania

Location

Republican Clinical Oncology Center

Kazan', 420029, Russia

Location

Pyatigorsk Interdistric Oncology Center

Pyatigorsk, 357502, Russia

Location

Oncology Center of Moskovskiy District

Saint Petersburg, 196247, Russia

Location

AV Medical Group

Saint Petersburg, 197082, Russia

Location

Palliative Care Center Devita

Saint Petersburg, 197183, Russia

Location

City Clinical Oncology Center

Saint Petersburg, 198255, Russia

Location

Samara Regional Clinical Oncology Center

Samara, 443031, Russia

Location

Ogaryov Mordovia National Research State University, Republican Oncology Center

Saransk, 430032, Russia

Location

Oncology Center #2

Sochi, 354057, Russia

Location

Volgograd Regional Clinical Oncology Center

Volgograd, 400138, Russia

Location

Publ Non- Profit Ent. under Kharkiv Reg. Council

Kharkiv, Kharkiev Region, 61166, Ukraine

Location

Communal Non-Profit Enterprise "Regional Center of Oncology"

Kharkiv, Kharkiev, 61070, Ukraine

Location

Medical Center "VERUM" Limited Liability Company

Kyiv, Kyviv, 3039, Ukraine

Location

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

Poltava, Poltava Oblast, 36011, Ukraine

Location

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

Dnipro, 49055, Ukraine

Location

Private Enterprise "First Private Clinic"

Kyiv, 03037, Ukraine

Location

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

Ternopil, 46023, Ukraine

Location

Medical Center of Limited Liability Company "ONCOLIFE"

Zaporizhzhya, 69059, Ukraine

Location

MeSH Terms

Conditions

Cachexia; Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Weight Loss; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Thinness; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Florin Muraru
• Organization: Helsinn Healthcare SA

florin.muraru@helsinn.com

+41 91985 21 21

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This was a double-blind study. The blinding of the study drugs was guaranteed by the use of anamorelin HCl film-coated tablets and matching placebo tablets. Patients were randomized using the Interactive Web Response System (IWRS). Any unblinding of the study treatment was performed using the IWRS.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blind, Placebo-Controlled, Multicenter Study

Study Record Dates

• First Submitted: November 14, 2018
• First Posted: November 15, 2018
• Study Start: May 6, 2019
• Primary Completion: December 27, 2022
• Study Completion: December 27, 2022
• Last Updated: June 26, 2024
• Results First Posted: June 26, 2024

Record last verified: 2024-06

Locations

RO (7); CR (3); UA (8); PL (7); AU (6); RU (10); US (19); BE (5)