Safety and Efficacy of Anamorelin HCl in Patients With Non-Small Cell Lung Cancer-Cachexia (ROMANA 1)

• ClinicalTrials.gov Identifier: NCT01387269
• Recruitment Status: Completed
• First Posted: July 4, 2011
• Results First Posted: July 11, 2017
• Last Update Posted: October 27, 2017
• Sponsor: Helsinn Therapeutics (U.S.), Inc
• Information provided by (Responsible Party): Helsinn Therapeutics (U.S.), Inc

Tracking Information

• First Submitted Date: June 30, 2011
• First Posted Date: July 4, 2011
• Results First Submitted Date: March 15, 2017
• Results First Posted Date: July 11, 2017
• Last Update Posted Date: October 27, 2017
• Study Start Date: July 2011
• Actual Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 9, 2017)

• Change in Lean Body Mass [ Time Frame: Change in Lean Body Mass from Baseline Over 12 Weeks ]
  Change in Lean Body Mass (LBM) from baseline over 12 weeks for the ITT Population. Change from baseline over 12 weeks was defined as the average of the change from baseline at Week 6 and the change from baseline at Week 12.
• Change in Handgrip Strength [ Time Frame: Change in Handgrip Strength of the Non-Dominant Hand from Baseline Over 12 Weeks ]
  Change in Handgrip Strength (HGS) of the non-dominant hand from baseline over 12 weeks for the ITT Population. Change from baseline over 12 weeks was defined as the average of the change from baseline at Week 6 and the change from baseline at Week 12.

Original Primary Outcome Measures (submitted: June 30, 2011)

• Evaluate the effect of Anamorelin on lean body mass as measured by DXA scan [ Time Frame: 12 weeks ]
• Evaluate the effect of Anamorelin on muscle strength as measured by hand-grip strength [ Time Frame: 12 weeks ]

Current Secondary Outcome Measures (submitted: June 9, 2017)

• Change in A/CS Domain Score [ Time Frame: Change in FAACT A/CS Domain Score from Baseline Over 12 Weeks ]
  The Functional Assessment of Anorexia/Cachexia Treatment (FAACT) Additional Concerns Subscale (A/CS domain) is a 12-item scale that is part of the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System. Each item is answered on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). The 12-items are summed together to obtain the domain score. Note that negatively phrased questions are reverse scored so that higher scores always represent improvement/less symptom burden. The total possible score for the A/CS domain ranges from 0 (worst) to 48 (best).
• Change in FACIT-F Fatigue Domain Score [ Time Frame: Change in FACIT-F Fatigue Domain Score from Baseline Over 12 Weeks ]
  The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) fatigue domain is a 13-item scale that is part of the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System. Each item is answered on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). The 13-items are summed together to obtain the domain score. Note that negatively phrased questions are reverse scored so that higher scores always represent improvement/less symptom burden. The total possible score for the FACIT-F fatigue domain ranges from 0 (worst) to 52 (best).
• Change in Body Weight [ Time Frame: Change in Body Weight from Baseline Over 12 Weeks ]
  Change in body weight (BW) from baseline overall (i.e., over 12 weeks) for the MITT Population.

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

Descriptive Information

• Brief Title: Safety and Efficacy of Anamorelin HCl in Patients With Non-Small Cell Lung Cancer-Cachexia (ROMANA 1)
• Official Title: Anamorelin HCl in the Treatment of Non-Small Cell Lung Cancer-Cachexia (NSCLC-C): A Randomized Double-Blind Placebo-Controlled Multicenter Phase III Study to Evaluate the Safety and Efficacy of Anamorelin HCl in Patients With NSCLC-C
• Brief Summary: The administration of Anamorelin in patients with Stage III-IV non-small cell lung cancer-cachexia (NSCLC-C) is expected to increase appetite, lean body mass, weight gain, and muscle strength.
• Detailed Description: This is a randomized, double-blind, placebo-controlled, multicenter study to assess the safety and efficacy of Anamorelin in patients with non-small cell lung cancer-cachexia (NSCLC-C). The primary efficacy analysis will include the treatment difference in the change in lean body mass and physical function. Pharmacokinetic (PK) samples will also be collected at Day 43 visit for population PK.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Cachexia
• Non-Small Cell Lung Cancer

Intervention

• Drug: Anamorelin HCl
  Anamorelin HCl will be orally administered daily at least one hour before meal
• Drug: Placebo
  Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before meal

Study Arms

• Experimental: 100 mg QD
  Anamorelin HCL 100 mg will be administered daily
  Intervention: Drug: Anamorelin HCl
• Placebo Comparator: Placebo
  Placebo tablets identical in appearance to active tablets; oral administration once daily
  Intervention: Drug: Placebo

Publications *

• Currow D, Temel JS, Abernethy A, Milanowski J, Friend J, Fearon KC. ROMANA 3: a phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer (NSCLC) patients with cachexia. Ann Oncol. 2017 Aug 1;28(8):1949-1956. doi: 10.1093/annonc/mdx192.
• Temel JS, Abernethy AP, Currow DC, Friend J, Duus EM, Yan Y, Fearon KC. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol. 2016 Apr;17(4):519-531. doi: 10.1016/S1470-2045(15)00558-6. Epub 2016 Feb 20.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 17, 2015): 484
• Original Estimated Enrollment (submitted: June 30, 2011): 477
• Actual Study Completion Date: February 2015
• Actual Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Documented diagnosis of unresectable Stage III or Stage IV NSCLC
• Patients may be receiving maintenance chemotherapy
• Patients planning to initiate a new chemotherapy and/or radiation therapy regimen may do so only within ± 14 days of randomization
• Patients may have completed a chemotherapy and/or radiation therapy and/or have no plan to initiate a new regimen within 12 weeks from randomization; at least 14 days must elapse from the completion of the chemotherapy and/or radiation therapy prior to randomization
• Involuntary weight loss of ≥5% body weight within 6 months prior to screening or a screening body mass index (BMI) <20 kg/m2
• Body mass index ≤30 kg/m2
• Life expectancy of >4 months at time of screening
• ECOG performance status ≤2
• Adequate hepatic function, defined as AST and ALT levels ≤5 x upper limit of normal
• Adequate renal function, defined as creatinine ≤2 x upper limit of normal, or calculated creatinine clearance >30 ml/minute
• Ability to understand and comply with the procedures for the HGS evaluation
• If a woman of childbearing potential or a fertile man, he/she must agree to use an effective form of contraception during the study and for 30 days following the last dose of study drug (an effective form of contraception is abstinence, a hormonal contraceptive, or a double-barrier method)
• Must be willing and able to give signed informed consent and, in the opinion of the Investigator, to comply with the protocol tests and procedures

Exclusion Criteria:

• Other forms of lung cancer (e.g., small cell, mesothelioma)
• Women who are pregnant or breast-feeding
• Known HIV, hepatitis (B&C), or active tuberculosis
• Had major surgery (central venous access placement and tumor biopsies are not considered major surgery) within 4 weeks prior to randomization; patients must be well recovered from acute effects of surgery prior to screening; patients should not have plans to undergo major surgical procedures during the treatment period
• Currently taking prescription medications intended to increase appetite or treat weight loss; these include, but are not limited to, testosterone, androgenic compounds, megestrol acetate, methylphenidate, and dronabinol
• Inability to readily swallow oral tablets; patients with severe gastrointestinal disease (including esophagitis, gastritis, malabsorption, or obstructive symptoms) or intractable or frequent vomiting are excluded
• Has an active, uncontrolled infection
• Has uncontrolled diabetes mellitus
• Has untreated clinically relevant hypothyroidism
• Has known or symptomatic brain metastases
• Receiving strong CYP3A4 inhibitors within 14 days of randomization
• Receiving tube feedings or parenteral nutrition (either total or partial); patients must have discontinued these treatments for at least 6 weeks prior to Day 1, and throughout the study duration
• Other clinical diagnosis, ongoing or intercurrent illness that in the Investigator's opinion would prevent the patient's participation
• Has had previous exposure to Anamorelin HCl
• Patients actively receiving a concurrent investigational agent

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belarus, Belgium, Canada, Czechia, France, Germany, Hungary, Italy, Netherlands, Poland, Russian Federation, Serbia, Slovenia, Spain, Ukraine, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01387269
• Other Study ID Numbers: HT-ANAM-301
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Helsinn Therapeutics (U.S.), Inc
• Original Responsible Party: John Friend, MD, Sr. Vice President, R&D, Helsinn Therapeutics (U.S.), Inc.
• Current Study Sponsor: Helsinn Therapeutics (U.S.), Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Helsinn Therapeutics (U.S.), Inc
• Verification Date: September 2017