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)

• ClinicalTrials.gov Identifier: NCT03743064
• Recruitment Status: Recruiting
• First Posted: November 15, 2018
• Last Update Posted: December 4, 2020
• Sponsor: Helsinn Healthcare SA
• Information provided by (Responsible Party): Helsinn Healthcare SA

Tracking Information

• First Submitted Date: November 14, 2018
• First Posted Date: November 15, 2018
• Last Update Posted Date: December 4, 2020
• Actual Study Start Date: December 18, 2018
• Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 14, 2018)

Composite Clinical Response (CCR) [ Time Frame: from baseline to week 9 ]

CCR is a composite measure including both a ≥ 5% body weight gain from baseline and increase ≥ 2 points (meaning a clinically relevant improvement) in the 5-item Anorexia Symptom Scale score from baseline) in patients who survive until Day 64.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 15, 2018)

• body weight [ Time Frame: from baseline to week 9 ]
  Change in body weight from baseline to Week 9
• 5 item Anorexia Symptom Scale [ Time Frame: from baseline to week 9 ]
  Change in patient-reported anorexia symptoms from baseline to Week 9 as measured by the 5 item Anorexia Symptom Scale. The 5 item Anorexia Symptom Scale ranges from 0 to 20, higher score indicates better condition regarding anorexia symptoms.
• FAACT total score [ Time Frame: from baseline to week 9 ]
  Change in FAACT total score from baseline to week 9. FAACT total score (Functional Assessment of Anorexia Cachexia Treatment total score) is the sum of the scores FACT-G (Functional Assessment of Cancer Therapy - General) and FAACT A/CS domain (Functional Assessment Anorexia Cachexia Therapy Anorexia Cachexia Subscale domain). The FACT-G is the sum of the Physical Well-Being (ranging from 0 to 28), the Social/Family Well-Being (ranging from 0 to 28), the Emotional Well-Being (ranging from 0 to 24) and the Functional Well-Being (ranging from 0 to 28). The FAACT A/CS domain ranges from 0 to 48. The FAACT total score ranges from 0 to 156, higher score indicates better condition.

Original Secondary Outcome Measures (submitted: November 14, 2018)

• body weight [ Time Frame: from baseline to week 9 ]
  Change in body weight from baseline to Week 9
• 5 item Anorexia Symptom Scale [ Time Frame: from baseline to week 9 ]
  Change in patient-reported anorexia symptoms from baseline to Week 9 as measured by the 5 item Anorexia Symptom Scale
• FAACT total score [ Time Frame: from baseline to week 9 ]
  Change in FAACT total score from baseline to Week 9

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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)
• Brief 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized, Double-Blind, Placebo-Controlled, Multicenter Study

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition

• Cachexia; Cancer
• Non Small Cell Lung Cancer

Intervention

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

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 14, 2018): 316
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2022
• Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)

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.
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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Edwin De Wit, MD; 0041919852161; edwin.dewit@helsinn.com

• Listed Location Countries: Australia, Belgium, Croatia, Poland, Romania, Russian Federation, Ukraine, United States

Administrative Information

• NCT Number: NCT03743064
• Other Study ID Numbers: ANAM-17-21; 2018-002927-40 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Helsinn Healthcare SA
• Study Sponsor: Helsinn Healthcare SA
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Helsinn Healthcare SA
• Verification Date: December 2020