Multicenter, randomized, double-blind, placebo-controlled, phase III clinical trial to investigate the efficacy and safety of Dronabinol in the Improvement of ChemOthErapy-induced and tumor-Related symptoms in patients with locally advanced or metastatic pancreatic cancer during first-line chemotherapy.
Short title: AGMT_DISCOVER
Title: Multicenter, randomized, double-blind, placebo-controlled, phase III clinical trial to investigate the efficacy and safety of Dronabinol in the Improvement of ChemOthErapy-induced and tumor-Related symptoms in patients with locally advanced or metastatic pancreatic cancer during first-line chemotherapy.
Start: November 2019
Coordinating Investigator: Univ. Prof. Dr. Felix Keil
EudraCT Number: 2019-000616-28
Number of patients: 140
Sponsor: AGMT gemeinnützige GmbH
This is a multicenter, randomized, double-blind, placebo-controlled clinical trial to investigate the efficacy and safety of dronabinol in the improvement of chemotherapy-induced and tumor-related symptoms in patients with advanced pancreatic cancer during first-line chemotherapy.
The primary endpoint variable is the standardized area under the curve of the EORTC QLQ-C30 symptom summary score over the on-treatment period (visit 1-9).
Secondary endpoints will be evaluated by comparison of the two treatment groups.
- Standardized area under the curve of the EORTC QLQ-C30 symptom summary score over the maintenance period scores at visits 3-9
- Change of EORTC QLQ-C30 symptom summary score from baseline to visit 9
- Symptom scales of EORTC QLQ-C30 such as fatigue, pain, nausea and vomiting, dyspnoea, insomnia, appetite loss, constipation and diarrhea
- Global quality of life of the EORTC QLQ-C30
- Functional scales of the EORTC QLQ-C30 such as physical, role, cognitive, emotional and social
Mean change from baseline of the Glasgow Prognostic Score and from baseline of serum levels of the score-defining biomarkers C-reactive protein (CRP) and albumin
- Amount of concomitant medication taken with special focus on antiemetic, psychotropic and pain medication
- Mean time to critical weight-loss (5%) after the 16 weeks treatment period assessed with a standard scale
- Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameters: Lean body mass (LBM = Fat free mass FFM), Total body water (TBW), Fat mass (FM), Body cell mass (BCM), Extracellular mass (ECM), Phase angle (PA), Resistance (Rz), Reactance (Xc)(1)
- Mean change from baseline of muscle strength measured by hand-grip strength test
Proportion of patients not adhering to individual baseline chemotherapy regime (dose and time frame)
- Chemotherapeutic dose intensity over the treatment period of 18 weeks
- Frequency and severity of adverse events (AE) and serious adverse events (SAEs) assessed with Common Toxicity Criteria for Adverse Events (NCI-CTCAE V5.0)
- Incidence of adverse drug reactions (ARs)
- Progression-free survival (PFS) from treatment start until progression or death from any cause and overall survival (OS) from treatment start until death from any cause
- Male and female subjects aged ≥18
- Patients with diagnosis of locally advanced or metastatic pancreatic cancer, eligible for first-line chemotherapy
Note: the decision for chemotherapy treatment has to be taken prior to screening and independently from the decision to participate in this clinical trial
- According to investigator life expectancy of > 4 months at screening
- Female patients must either be post-menopausal or surgically sterilized or use a highly effective method of birth control (hormonal contraceptives, intra–uterine devices, or diaphragms with spermicide) for the duration of the study and/or must have a negative pregnancy test (female patients with childbearing potential only)
- Willing and able to provide written informed consentWritten informed consent given prior to any trial-related procedure not part of the normal medical practice
Exclusion criteria (selected):
- Ineligible for chemotherapy treatment with FOLFIRINOX or Gemcitabine+Abraxane®
- Use of dronabinol or cannabis-based medicine with THC as constituent within 6 months before screening. A urine drug test will be performed during screening phase.
- Use of marihuana within the last 4 weeks and unwillingness to abstain for the duration of the study. A urine drug test will be performed during screening phase.
- Currently receiving chemotherapy or anticipated use of chemotherapy due to any condition not related to locally advanced or metastatic pancreatic cancer
- Known current or past (within the last year prior to screening) alcohol, narcotics or drug abuse
- Patients unable or unwilling to waive driving motor vehicles or using machines especially during titration period