Cachexia, Non-Small Cell Lung Cancer
Conditions
Brief summary
The administration of Anamorelin HCl in patients with 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, parallel-group, placebo-controlled, extension study to assess the safety and efficacy of Anamorelin HCl in NSCLC-C patients.
Interventions
DRUGAnamorelin HCl
DRUGPlacebo
Sponsors
Helsinn Therapeutics (U.S.), Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has completed the Day 85 Visit in the original trial (Study HT-ANAM-301 or HT-ANAM-302) and is considered appropriate to continue to receive additional study drug; must start dosing on the extension study within 5 days of completing dosing on the original trial * ECOG performance status ≤2 * Life expectancy of \>4 months at time of screening * If 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
* Women who are pregnant or breast-feeding * Had major surgery (central venous access placement and tumor biopsies are not considered major surgery) within 4 weeks prior to enrollment into the extension study; 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 known or symptomatic brain metastases * Receiving strong CYP3A4 inhibitors * 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 * Patients actively receiving a concurrent investigational agent, other than Anamorelin HCl
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events | Over the 12-week treatment period | To Evaluate the Safety and Tolerability of Anamorelin HCl. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight | Change in body weight from baseline of the original trial through Week 12 of this extension trial. | — |
| Change in Handgrip Strength of the Non-Dominant Hand | Change in HGS from baseline of the original trial through Week 12 of this extension trial. | — |
| Change in A/CS Domain Score | Change in FAACT A/CS Domain Score from baseline of the original trial through Week 12 of this extension trial | Change in the Functional Assessment of Anorexia/Cachexia Treatment (FAACT) 12-item Additional Concerns Subscale (A/CS) domain score is a 12-item scale. 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). |
Countries
Australia, Belarus, Belgium, Canada, Czechia, France, Germany, Hungary, Israel, Italy, Poland, Russia, Serbia, Slovenia, Spain, Ukraine, United States
Participant flow
Recruitment details
Patients who completed dosing in either of the original trials of anamorelin HCl in the treatment of NSCLC-C (HT-ANAM-301 or HT-ANAM-302) were able to enroll in this study and continue to receive the study drug to which they were assigned, either anamorelin HCl 100 mg or placebo QD for an additional 12 weeks.
Pre-assignment details
The primary purpose of this extension study was to permit patients who completed dosing in the original 12-week trials to have the option of continuing to receive randomized study drug for an additional 12 weeks, to further evaluate the safety and tolerability of anamorelin HCl.
Participants by arm
| Arm | Count |
|---|---|
| Anamorelin HCl Active drug; 100 mg tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day. | 345 |
| Placebo Placebo tablets identical in appearance to active tablets; oral administration QD for 12 weeks, at least 1 hour before the first meal of the day. | 168 |
| Total | 513 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 23 | 17 |
| Overall Study | Lost to Follow-up | 6 | 2 |
| Overall Study | Other | 9 | 3 |
| Overall Study | Study drug-related AE | 1 | 0 |
| Overall Study | Unrelated to study drug AE | 6 | 1 |
| Overall Study | Withdrawal by patient | 27 | 14 |
Baseline characteristics
| Characteristic | Placebo | Total | Anamorelin HCl |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 48 Participants | 157 Participants | 109 Participants |
| Age, Categorical Between 18 and 65 years | 120 Participants | 356 Participants | 236 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 166 Participants | 510 Participants | 344 Participants |
| Region of Enrollment Australia | 3 participants | 10 participants | 7 participants |
| Region of Enrollment Belarus | 6 participants | 14 participants | 8 participants |
| Region of Enrollment Belgium | 2 participants | 4 participants | 2 participants |
| Region of Enrollment Canada | 1 participants | 4 participants | 3 participants |
| Region of Enrollment Czech Republic | 3 participants | 14 participants | 11 participants |
| Region of Enrollment France | 2 participants | 3 participants | 1 participants |
| Region of Enrollment Germany | 0 participants | 3 participants | 3 participants |
| Region of Enrollment Hungary | 16 participants | 55 participants | 39 participants |
| Region of Enrollment Israel | 2 participants | 6 participants | 4 participants |
| Region of Enrollment Italy | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Netherlands | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Poland | 60 participants | 167 participants | 107 participants |
| Region of Enrollment Russian Federation | 31 participants | 100 participants | 69 participants |
| Region of Enrollment Serbia | 2 participants | 6 participants | 4 participants |
| Region of Enrollment Slovenia | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Spain | 2 participants | 7 participants | 5 participants |
| Region of Enrollment Ukraine | 33 participants | 97 participants | 64 participants |
| Region of Enrollment United States | 4 participants | 20 participants | 16 participants |
| Sex: Female, Male Female | 43 Participants | 126 Participants | 83 Participants |
| Sex: Female, Male Male | 125 Participants | 387 Participants | 262 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 94 / 343 | 57 / 167 |
| serious Total, serious adverse events | 44 / 343 | 21 / 167 |
Outcome results
Primary
Percentage of Participants With Treatment-emergent Adverse Events
To Evaluate the Safety and Tolerability of Anamorelin HCl.
Time frame: Over the 12-week treatment period
Population: Safety Population, defined as patients who received any extension trial study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anamorelin HCl | Percentage of Participants With Treatment-emergent Adverse Events | 52 percentage of participants |
| Placebo | Percentage of Participants With Treatment-emergent Adverse Events | 56 percentage of participants |
Secondary
Change in A/CS Domain Score
Change in the Functional Assessment of Anorexia/Cachexia Treatment (FAACT) 12-item Additional Concerns Subscale (A/CS) domain score is a 12-item scale. 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).
Time frame: Change in FAACT A/CS Domain Score from baseline of the original trial through Week 12 of this extension trial
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Anamorelin HCl | Change in A/CS Domain Score | 4.46 scores on a scale | Standard Error 0.92 |
| Placebo | Change in A/CS Domain Score | 3.24 scores on a scale | Standard Error 1.01 |
Secondary
Change in Body Weight
Time frame: Change in body weight from baseline of the original trial through Week 12 of this extension trial.
Population: Intent-to-Treat Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Anamorelin HCl | Change in Body Weight | 3.06 kg | Standard Error 0.631 |
| Placebo | Change in Body Weight | 0.92 kg | Standard Error 0.697 |
Secondary
Change in Handgrip Strength of the Non-Dominant Hand
Time frame: Change in HGS from baseline of the original trial through Week 12 of this extension trial.
Population: Intent-to-Treat Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Anamorelin HCl | Change in Handgrip Strength of the Non-Dominant Hand | -0.83 kg | Standard Error 0.929 |
| Placebo | Change in Handgrip Strength of the Non-Dominant Hand | -0.55 kg | Standard Error 1.036 |