Cachexia
Conditions
Keywords
NSCLC, anorexia, cachexia, grip strength, lean body mass
Brief summary
Cachexia is a presentation of a chronic manifestation of acute metabolic stress, a hypercatabolic nutritional state in which the normal fat and protein sparing mechanisms are not functioning and increased nutrition is not utilized. To switch the nutritional system from a hypercatabolic to a normal nutritional state, therapy must block multi-factorial stress signaling a threshold of activation. Consistent with the synergistic hypothesis, propranolol and etodolac have been evaluated in subjects with advanced cancer demonstrating cachexia. This trial will evaluate the safety and efficacy of VT-122 in subjects with NSCLC who have hypercatabolic cachexia.
Detailed description
The objective of this trial is to evaluate the safety and dose tolerability of VT-122 regimen and to evaluate the efficacy of VT-122 regimen This trial is to be conducted on patients who have a diagnosis of Stage IV NSCLC, are not on chemotherapy, have lost 5% of their body weight in the previous 2 months and are deemed to be hypercatabolic.
Interventions
DRUGVT-122 high dose
VT-122 high dose, dose escalated
DRUGVT-122 low dose
VT-122 low dose, dose escalated
Sponsors
Vicus Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with NSCLC * Demonstrating average weight loss of 5% within 2 months prior to enrollment * Heart rate of 72 bpm or greater * Negative pregnancy test (female patients of child bearing age) * Able to give informed consent * Able to be administered medication * Able to take food and defined nutritional support * Have not been on beta-blockers for a minimum of 1 week prior to administration of the medication screening dose * Have not undergone surgery for at least 2 weeks prior to entry into trial * Have not been on chemotherapy, immunotherapy, biologic therapy, radio therapy, and experimental therapy for a minimum of two weeks prior to medication screening dose and during their participation in this trial * An expected survival for a minimum of 12 weeks
Exclusion criteria
* Contraindication to nonsteroidal antiinflammatory drugs (NSAIDs) and beta blockers * Blood pressure less than 100/65 * Weight loss of 15% within 2 months prior to recruitment * Hypersensitivity reaction to the active components in VT-122 * History of myocardial infraction within the past 3 months * Congestive heart failure (as determined by symptoms and ECG) * A-V block of second or third degree * Unstable angina * Uncontrolled diabetes * Unable to be assessed for grip strength * A positive pregnancy test * Chronic infection or sepsis * History of bleeding disorders * Patients with peripheral edema * Patients on digoxin or other chronotropic drugs * Patients with evidence of severe dehydration * Patients with evidence of ascites
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Subjects With a Positive Change From Baseline to Week 4 in Lean Body Mass | 4 weeks |
| Proportion of Subjects With a Positive Change From Baseline to Week 4 in Grip Strength | 4 weeks |
Countries
India, United States
Participant flow
Recruitment details
First patient visit: March 23, 2007 Last patient visit: December 10, 2008
Participants by arm
| Arm | Count |
|---|---|
| Group A, Control Group Supportive care only | 12 |
| Group B, Low Dose VT-122 VT-122 (dose of etodolac: 400 mg/day) + supportive care | 12 |
| Group C, High Dose VT-122 VT-122 (dose of etodolac: 800 mg/day) + supportive care | 13 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Death | 0 | 3 | 1 |
| Overall Study | Intercurrent Medical Illness | 0 | 1 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 0 | 1 |
Baseline characteristics
| Characteristic | Group A, Control Group | Group B, Low Dose VT-122 | Group C, High Dose VT-122 | Total |
|---|---|---|---|---|
| Age Continuous | 54.1 years STANDARD_DEVIATION 12 | 55.1 years STANDARD_DEVIATION 7.6 | 57.6 years STANDARD_DEVIATION 10.4 | 55.7 years STANDARD_DEVIATION 10.1 |
| Region of Enrollment India | 12 participants | 12 participants | 13 participants | 37 participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 3 Participants | 12 Participants |
| Sex: Female, Male Male | 9 Participants | 6 Participants | 10 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 12 | 9 / 12 | 10 / 13 |
| serious Total, serious adverse events | 0 / 12 | 4 / 12 | 3 / 13 |
Outcome results
Primary
Proportion of Subjects With a Positive Change From Baseline to Week 4 in Grip Strength
Time frame: 4 weeks
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Group A, Control Group | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Grip Strength | >0% to <5% | 3 participants | — |
| Group A, Control Group | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Grip Strength | <=0% | 4 participants | 4.03 |
| Group A, Control Group | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Grip Strength | >=5% | 5 participants | — |
| Group B, Low Dose VT-122 | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Grip Strength | >0% to <5% | 1 participants | — |
| Group B, Low Dose VT-122 | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Grip Strength | <=0% | 8 participants | 3.56 |
| Group B, Low Dose VT-122 | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Grip Strength | >=5% | 3 participants | — |
| Group C, High Dose VT-122 | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Grip Strength | <=0% | 7 participants | 6.25 |
| Group C, High Dose VT-122 | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Grip Strength | >=5% | 4 participants | — |
| Group C, High Dose VT-122 | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Grip Strength | >0% to <5% | 2 participants | — |
Primary
Proportion of Subjects With a Positive Change From Baseline to Week 4 in Lean Body Mass
Time frame: 4 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A, Control Group | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Lean Body Mass | >0% to <5% | 3 participants |
| Group A, Control Group | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Lean Body Mass | >=5% | 1 participants |
| Group A, Control Group | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Lean Body Mass | <=0% | 8 participants |
| Group A, Control Group | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Lean Body Mass | Data Missing | 0 participants |
| Group B, Low Dose VT-122 | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Lean Body Mass | >0% to <5% | 3 participants |
| Group B, Low Dose VT-122 | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Lean Body Mass | <=0% | 6 participants |
| Group B, Low Dose VT-122 | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Lean Body Mass | >=5% | 3 participants |
| Group B, Low Dose VT-122 | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Lean Body Mass | Data Missing | 0 participants |
| Group C, High Dose VT-122 | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Lean Body Mass | >=5% | 4 participants |
| Group C, High Dose VT-122 | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Lean Body Mass | <=0% | 5 participants |
| Group C, High Dose VT-122 | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Lean Body Mass | >0% to <5% | 3 participants |
| Group C, High Dose VT-122 | Proportion of Subjects With a Positive Change From Baseline to Week 4 in Lean Body Mass | Data Missing | 1 participants |