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 (DIsCOvER)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 109
- 试验地点
- 11
- 主要终点
- Standardized area under the curve of the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 symptom summary score over the on-treatment period.
研究概览
简要总结
Aim of this phase III trial is to investigate the efficacy and safety of dronabinol (orally administered tetrahydrocannabinol (THC)) as adjuvant therapy to first-line standard chemotherapy in patients with metastatic pancreatic cancer for improvement of chemotherapy- and tumor-related symptoms applicated by individual titration up to the maximum tolerated dose.
详细描述
Patients with pancreatic cancer suffer from multiple symptoms related to the tumor itself or induced by the chemotherapy. The available supportive therapy is still not able to relief all symptoms that are caused by the malignancy itself as well as by the antineoplastic therapy.
Additionally, anorexia and weight loss, that often result in increased morbidity and mortality in this patient population as well as in psycho-social burden and suffering in patients and their relatives, are unmet needs in pancreatic cancer patients.
Therapeutic approaches focus on treating the malignancy itself, additional nutritional support and physical examination might prevent patients from further side effects such as sarcopenia.
During the last decades a number of appetite-modulating drugs have been under clinical investigation. A number of studies focused on the endocannabinoid system, which is involved amongst others in appetite-modulating, antiemetic, analgesic and anti-inflammatory processes.
As dronabinol is already used as magistral formulation, its beneficial effect has often been observed in these patients in the clinical routine, especially in patients with therapy-refractory nausea and emesis. Due to its broad efficacy it might be of benefit for patients suffering from malignancy. Thus, investigators want to evaluate the efficacy of dronabinol in the improvement of chemotherapy-induced and tumor-related symptoms in advanced pancreatic patients during systemic first-line chemotherapy. However, data on optimal dosage are conflicting yet.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects aged ≥18
- •Patients with diagnosis of locally advanced, inoperable or metastatic pancreatic cancer, eligible for first-line chemotherapy with FOLFIRINOX or gemcitabine+Abraxane®
- •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 consent.
- •Written informed consent given prior to any trial-related procedure not part of the normal medical practice.
排除标准
- •Patients who are members of the staff of the trial center, staff of the sponsor or CRO, the investigator him/herself or close relatives of the investigator.
- •Simultaneous participation in another interventional clinical trial, participation in another trial with less than 30 days or five half-lives of the IMP (whatever is longer) to screening, or previous participation in this trial.
- •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
- •History of or existing cardiac diseases or pathological findings (e.g. chronic insufficiency NYHA III/IV, severe arrhythmia, unstable angina pectoris, myocardial infarction within the past 6 months, significant QT-prolongation etc.), which in the opinion of the investigator might interfere with the safety or tolerability of the study treatment. An ECG has to be done to exclude pathological findings and must not be older than 3 months before screening or if none is available, has to be performed during the screening phase and assessed prior to randomization
- •Clinically relevant, severe pulmonary diseases, uncontrolled hypertension, or poorly controlled diabetes
- •History of or existing relevant CNS and/or psychiatric disorders (e.g. schizophrenia, psychosis, manic and/or depressive disorders, suicidal ideations, etc) which might interfere with the safety or tolerability of the study treatment. Patients with reactive depression are not excluded from participation.
- •Known current or past (within the last year prior to screening) alcohol, narcotics or drug abuse
- •Pregnancy or breast feeding
- •Known allergy to cannabinoids and other constituents of the investigational medicinal product
- •Intake of prohibited concomitant medication
- •Any other substantial medical condition that in the opinion of the investigator could create undue risk to the subject or could affect adherence with the trial protocol
- •Legal incapacity, limited legal capacity or any other condition which makes the subject unable to understand the subject information and informed consent form (ICF)
- •Patients unable or unwilling to waive driving motor vehicles or using machines especially during titration period
- •Unable or unwilling to comply with the protocol regulations
研究组 & 干预措施
Dronabinol
BX-1 contains 25 mg dronabinol/ml (2.5% delta-9-trans-tetrahydrocannabinol = THC), oral solution; three applications per day from 2.5 mg (3 x 1 droplet) up to 30 mg (3 x 12 droplets)
干预措施: Dronabinol in Oral Dosage Form (Drug)
Placebo
Placebo: oral solution with cannabis flavor without active substance and otherwise identical to active comparator, three applications per day from 3 x 1 droplet up to 3 x 12 droplets
干预措施: Placebo in Oral Dosage Form (Drug)
结局指标
主要结局
Standardized area under the curve of the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 symptom summary score over the on-treatment period.
时间窗: Prior to treatment start until end of 16 weeks maintenance treatment
The EORTC-QLQ-C30 is an integrated system for assessing the health-related quality of life (QoL) of cancer patients participating in international clinical trials. The validated QLQ-C30 summary score is calculated as mean score of the 13 of the 15 EORTC QLQ-C30 scales (v3.0), based on 27 of 30 items (the Financial Impact scale and Quality of Life score are not included). A high score for a symptom scale / item (fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea) represents a high level of symptomatology / problems. A high score for a functional scale (physical functioning, role functioning, cognitive functioning, emotional functioning, social functioning) represents a high / healthy level of functioning. Scores for individual items: "Not at All" = 1 point, "A Little" = 2 points, "Quite a Bit" = 3 points, "Very Much" = 4 points. A linear transformation is used to standardize the raw score, so that overall scores range from 0 to 100.
次要结局
- Change of European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 symptom summary score from baseline to summary score over the maintenance period(From treatment start until week 16)
- Standardized area under the curve of the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 symptom summary score over the maintenance period(After 4 weeks of treatment until week 16)
- Global quality of life of the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30(At baseline and 2-weekly until end of treatment at week 18)
- Symptom scales of European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30(At baseline and 2-weekly until end of treatment at week 18)
- Functional scales of the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30(At baseline and 2-weekly until end of treatment at week 18)
- Mean change from baseline of the Glasgow Prognostic Score(At baseline and at end of treatment at week 16)
- Amount of concomitant medication taken(From baseline until end of treatment at week 18)
- Mean time to critical weight-loss (5%)(From baseline until end of treatment at week 16)
- Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Lean body mass (LBM)(At baseline and at end of treatment at week 16)
- Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Total body water (TBW)(At baseline and at end of treatment at week 16)
- Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Fat mass (FM)(At baseline and at end of treatment at week 16)
- Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Body cell mass (BCM)(At baseline and at end of treatment at week 16)
- Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Extracellular mass (EM)(At baseline and at end of treatment at week 16)
- Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Reactance(Xc)(At baseline and at end of treatment at week 16)
- Mean change from baseline of muscle strength(At baseline and at end of treatment at week 16)
- Proportion of patients not adhering to individual baseline chemotherapy regimen(From baseline until end of treatment at week 18)
- Chemotherapeutic dose intensity over the treatment period of 18 weeks(From baseline until end of treatment at week 18)
- Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Phase angle (PA)(At baseline and at end of treatment at week 16)
- Mean changes from baseline for Bioelectrical Impedance Analysis (BIA) parameter Resistance (Rz)(At baseline and at end of treatment at week 16)
- Overall survival (OS)(From treatment start until death from any cause assessed up to week 22)
- Incidence of adverse drug reactions (ARs)(From baseline until safety visit at week 22)
- Progression-free survival (PFS)(From treatment start until the date of first documented progression or death from any cause assessed up to week 22)
- Frequency and severity of (serious) adverse events (S)AE(From baseline until safety visit at week 22)