A Randomized, Double-blind, and Placebo Controlled Multicenter Phase II Trial Evaluating Anamorelin in the Prevention of Cancer Induced-Weight Loss and Anorexia in Patients Receiving First-line Treatment of Advanced Pancreatic Cancer
Overview
- Phase
- Phase 2
- Intervention
- Anamorelin Hydrochloride
- Conditions
- Metastatic Pancreatic Cancer
- Sponsor
- Lahey Clinic
- Enrollment
- 4
- Locations
- 1
- Primary Endpoint
- Percent Weight Change From Baseline to Week 25
- Status
- Terminated
- Last Updated
- 5 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed written informed consent
- •Female or male ≥18 years of age
- •Documented histologic or cytologic diagnosis of American Joint Committee on Cancer (AJCC) unresectable or metastatic pancreatic adenocarcinoma
- •Body mass index \< 20 kg/m2 with involuntary weight loss or \>5% within 6 months prior to screening
- •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
- •Subjects eligible to receive first line palliative chemotherapy
- •ECOG performance status 0 or 1 at screening
- •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
- •Appropriate treatment with pancreatic enzyme replacement prior to trial initiation
- •Female subjects shall be:
Exclusion Criteria
- •Patient with other forms of pancreatic cancer (e.g. neuroendocrine tumors)
- •Patient undergoing major surgery within 4 weeks of randomization or plans to undergo major surgery during study period.
- •Women who are pregnant or breastfeeding
- •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
- •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)
- •Patient unable to swallow pills
- •Patient with history of bariatric surgery, gastrectomy, or malabsorption disorder (gastritis, esophagitis)
- •Patient with recent use of CYP3A4 inhibitors
- •Patient with current daily use of therapies that may increase the QRS interval durations
- •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)
Arms & Interventions
Anamorelin
Patients randomized to anamorelin HCL will take it daily for 24 weeks starting 3-5 days prior to chemotherapy
Intervention: Anamorelin Hydrochloride
Placebo
Patients randomized to placebo will take it daily for 24 weeks starting 3-5 days prior to chemotherapy
Intervention: Placebo
Outcomes
Primary Outcomes
Percent Weight Change From Baseline to Week 25
Time Frame: 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 Outcomes
- Anorexia Questionnaire(from baseline to week 13)
- Survival(25 weeks)
- Radiologic Response to Chemotherapy(from baseline to week 13)
- Weight Gain(from baseline to week 25 (end of the study))
- Fatigue Questionnaire(from baseline to week 13)
- Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0(from baseline to week 25 (end of study))
- Adverse Events(from baseline to week 25 (end of study))