Metastatic Pancreatic Cancer
Conditions
Keywords
Phase II, Randomized, double-blind, placebo-controlled, Anamorelin HCI, Cachexia, Anorexia, Weight loss, FAACT A/CS
Brief summary
Multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of anamorelin HCl. Approximately 100 subjects with advanced PDAC and cachexia will be randomized 1:1 to anamorelin HCl 100 mg or placebo, taken orally once daily (QD) for a total of 25 weeks. Subjects will be instructed to take the study drug at least 1 hour before their first meal of the day
Detailed description
Anorexia and cachexia are common clinical sequelae of uncontrolled, metastatic cancer. These effects can impair physical function, reduce quality of life, impair tolerability of anticancer therapy, and reduce survival. Anorexia and cachexia are especially challenging problems in patients diagnosed with metastatic pancreatic cancer. With an annual incidence approaching 50,000 patients in the U.S. alone, pancreatic cancer has an annual mortality of approximately 40,000 patients with most individuals succumbing to their disease within two years. Between 70-80% of patients with metastatic pancreatic cancer experience cancer cachexia, which has been associated with reduced survival, increased risk of disease progression, and impaired chemotherapy tolerance. Anamorelin HCl is an orally-active selective ghrelin receptor agonist which has shown anabolic and appetite-stimulating effects. Several randomized, double-blind, clinical trials in cancer patients have shown that anamorelin HCL is safe, efficacious and increases lean body mass, bodyweight, and appetite. Investigators propose to test anamorelin HCL administered with chemotherapy in the first-line treatment of locally advanced unresectable and metastatic pancreatic cancer. The study is a randomized, placebo controlled multicenter, Phase II trial to evaluate the efficacy and safety of anamorelin HCl. Approximately 100 patients with be enrolled in a 1:1 randomization to anamorelin HCL 100mg per day given concurrently with first-line chemotherapy compared to chemotherapy alone. Patients randomized to anamorelin HCL will take it daily for 24 weeks starting one day prior to chemotherapy. All patients will undergo an assessment by a certified nutritionist at or prior to their first cycle of chemotherapy. Both body weight and appetite will be measured at enrollment as well as at the initiation of chemotherapy. Patients will be stratified by degree of weight loss in the six months prior to enrollment, choice of first-line chemotherapy, and by baseline score of 5-item Anorexia Symptom Scale.
Interventions
Anamorelin HCl is an orally-active selective ghrelin receptor agonist which has shown anabolic and appetite-stimulating effects.
DRUGPlacebo
Anamorelin placebo
Sponsors
Helsinn Healthcare SA
Quartesian LLC
Lahey Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Masking description
double-blind. Neither the investigator nor the participant would know the assigned drug/placebo
Intervention model description
One group receives Anamorelin, and the other group receives placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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) unresectable or metastatic pancreatic adenocarcinoma 4. Body mass index \< 20 kg/m2 with involuntary weight loss or \>5% 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. Subjects eligible to receive first line palliative chemotherapy 7. ECOG performance status 0 or 1 at screening 8. Acceptable hepatic function as defined by total bilirubin \< 1.6 mg/dl unless associated with Gilbert syndrome, then total bilirubin \< 2 x ULN. AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN or if hepatic metastases are present ≤ 5 x ULN 9. Appropriate treatment with pancreatic enzyme replacement prior to trial initiation 10. Female subjects shall be: 1. of non-childbearing potential or 2. of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test within 24 hours prior to first dose of investigational product. 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 pancreatic cancer (e.g. neuroendocrine tumors) 2. Patient undergoing major surgery within 4 weeks of randomization or plans to undergo major surgery during study period. 3. Women who are pregnant or breastfeeding 4. Patient with alternative cause of cachexia as determined by the investigator including: a) severe COPD requiring O2, b) severe heart failure (NYHA Class III- IV), c) second malignancy 5. Reversible causes of reduced food intake as determined by the investigator including but not limited to: severe mucositis (\>=NCI CTCAE grade 3), mechanical obstruction, severe nausea, vomiting, or diarrhea (\>=NCI CTCAE grade 3) 6. Patient unable to swallow pills 7. Patient with history of bariatric surgery, gastrectomy, or malabsorption disorder (gastritis, esophagitis) 8. Patient with recent use of CYP3A4 inhibitors 9. Patient with current daily use of therapies that may increase the QRS interval durations 10. Patient currently taking medications/compounds intended to increase appetite or decrease weight loss (e.g. testosterone, megestrol acetate, cannabis products, methylphenidate, corticosteroids, olanzapine, mirtazapine (allowed if \>4 weeks of use as therapy for depression) 11. Patient with current use of tube feeding or parenteral feeding 12. Patient with pleural effusion requiring thoracentesis, pericardial effusion requiring drainage, edema or evidence of ascites 13. 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 14. Patient with uncontrolled diabetes mellitus or unmonitored diabetes mellitus 15. Patient with uncontrolled pain. 16. 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 17. Enrollment in a previous study with anamorelin HCl 18. Enrollment in another clinical trial during the time of this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Weight Change From Baseline to Week 25 | 25 weeks from baseline | Does anamorelin HCl dosed at 100mg per day vs. placebo demonstrate superiority on body weight gain and improvement in anorexia symptoms in patients undergoing first-line chemotherapy for incurable pancreatic cancer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anorexia Questionnaire | from baseline to week 13 | Absolute change in the Functional Assessment of Anorexia/Cachexia Treatment (FAACT 5) item Anorexia Symptom Score from baseline at week 13 |
| Survival | 25 weeks | Overall Survival |
| Radiologic Response to Chemotherapy | from baseline to week 13 | Chemotherapy response will be evaluated by RECIST criteria |
| Weight Gain | from baseline to week 25 (end of the study) | — |
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 | from baseline to week 25 (end of study) | expected toxicities for Chemotherapies (FOLFIRINOX and Gemcitabine/Nab-Paclitaxel) will be assessed by CTCAE v5.0 |
| Adverse Events | from baseline to week 25 (end of study) | Number of AEs that are definitely related to Anamorelin or Placebo. |
| Fatigue Questionnaire | from baseline to week 13 | Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire, fatigue subscale |
Other
| Measure | Time frame | Description |
|---|---|---|
| Unplanned Visits | From baseline to week 25 (end of the study) | Number of unplanned visits for symptom management as defined by unscheduled clinic visits, emergency department visits, or hospitalizations |
| Chemotherapy Dose Change | from baseline to week 13 | Percent change in dose intensity of chemotherapy as defined by percent reduction in anticipated chemotherapy dose as determined by the treating physician. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anamorelin Patients randomized to anamorelin HCL or placebo will take it daily for 24 weeks starting 3-5 days prior to chemotherapy.
Anamorelin Hydrochloride: Anamorelin HCl is an orally-active selective ghrelin receptor agonist which has shown anabolic and appetite-stimulating effects. | 2 |
| Placebo Patients randomized to anamorelin HCL or placebo will take it daily for 24 weeks starting 3-5 days prior to chemotherapy. | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Anamorelin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Continuous | 57.5 years | 75.5 years | 66.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 2 participants | 2 participants | 4 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 1 / 2 |
| other Total, other adverse events | 0 / 2 | 1 / 2 |
| serious Total, serious adverse events | 0 / 2 | 1 / 2 |
Outcome results
Primary
Percent Weight Change From Baseline to Week 25
Does anamorelin HCl dosed at 100mg per day vs. placebo demonstrate superiority on body weight gain and improvement in anorexia symptoms in patients undergoing first-line chemotherapy for incurable pancreatic cancer.
Time frame: 25 weeks from baseline
Population: No patients were analyzed for this outcome measure because no weight was collected at the 25-week time point.
Secondary
Adverse Events
Number of AEs that are definitely related to Anamorelin or Placebo.
Time frame: from baseline to week 25 (end of study)
Population: 2 patients on the anamorelin arm both withdrew, data was collected until withdraw of consent. One patient on the placebo arm ended the study prior to week 13 (data collected up until they ended) and another patient's data was analyzed through week 25.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anamorelin | Adverse Events | 0 of events |
| Placebo | Adverse Events | 0 of events |
Secondary
Anorexia Questionnaire
Absolute change in the Functional Assessment of Anorexia/Cachexia Treatment (FAACT 5) item Anorexia Symptom Score from baseline at week 13
Time frame: from baseline to week 13
Population: Upon review of collected data, no subjects completed the FAACT - 5 questionnaire at the week 13 visit. Three out of 4 patient were not on the study at the week 13 visit.
Secondary
Fatigue Questionnaire
Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire, fatigue subscale
Time frame: from baseline to week 13
Population: Upon review of collected data, 3 of 4 patients were no longer on the trial at week 13. The fourth patients' data was not collected.
Secondary
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0
expected toxicities for Chemotherapies (FOLFIRINOX and Gemcitabine/Nab-Paclitaxel) will be assessed by CTCAE v5.0
Time frame: from baseline to week 25 (end of study)
Population: 2 patients on the anamorelin arm both withdrew, data was collected until withdraw of consent. One patient on the placebo arm ended the study prior to week 13 (data collected up until they ended) and another patient's data was analyzed through week 25.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anamorelin | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 | 0 Participants |
| Placebo | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 | 1 Participants |
Secondary
Radiologic Response to Chemotherapy
Chemotherapy response will be evaluated by RECIST criteria
Time frame: from baseline to week 13
Population: RECIST data was not collected for any patient at the week 13 time point and therefore not analyzed for this outcome. Three out of the 4 patients were not on the study at week 13, and one patient's RECIST data was not collected due to site error.
Secondary
Survival
Overall Survival
Time frame: 25 weeks
Population: Unable to analyze the Anamorelin group since both patients withdrew consent. One patient in the Placebo arm ended the study prior to week 13 and could not be analyzed for this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Survival | 1 Participants |
Secondary
Weight Gain
Time frame: from baseline to week 25 (end of the study)
Population: Weight was not collected for 3 out of 4 patients since they were already removed from the trial by week 25 and the fourth patients' weight was not collected due to site error.
Other Pre-specified
Chemotherapy Dose Change
Percent change in dose intensity of chemotherapy as defined by percent reduction in anticipated chemotherapy dose as determined by the treating physician.
Time frame: from baseline to week 13
Population: Chemotherapy dose change data was not collected for any patient. This outcome measure was not analyzed.
Other Pre-specified
Unplanned Visits
Number of unplanned visits for symptom management as defined by unscheduled clinic visits, emergency department visits, or hospitalizations
Time frame: From baseline to week 25 (end of the study)
Population: Data for this outcome was not collected for any patient; no patients were analyzed.