Efficacy and Safety of Dronabinol in the Improvement of Chemotherapy-induced and Tumor-related Symptoms in Advanced Pancreatic Cancer

NCT03984214 | Completed Phase 3 DMC

• 1 other identifier: AGMT_DISCOVER
• Study Type: interventional
• Target: 109
• Locations: 2 countries
• Sites: 11

Brief Summary

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.

Conditions

Pancreatic Cancer Non-resectable; Chemotherapy-induced Nausea and Vomiting; Pancreatic Cancer Metastatic

Keywords

Dronabinol; THC; Placebo; Pancreatic Cancer; Chemotherapy-induced Nausea and Vomiting; Tumor related symptoms; Quality of life; EORTC QLQ-C30; FOLFIRINOX; Abraxane; Gemcitabine

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  Prior to treatment start until end of 16 weeks maintenance treatment

Secondary Outcomes (23)

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

Dronabinol

ACTIVE COMPARATOR

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)

Drug: Dronabinol in Oral Dosage Form

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo in Oral Dosage Form

Interventions

Dronabinol in Oral Dosage Form DRUG

Titration period for 4 weeks: titration according to tolerability from 2.5 mg (3 x 1 droplet) up to 30 mg (3 x 12 droplets) per day; dose increased by 2.5 mg (3 x 1 droplet) every other day Maintenance period for 12 weeks: individually tolerated maximum dose (up to 30 mg ≙ 3 x 12 droplets) at end of titration period will be continued for maintenance treatment Tapering period for 2 weeks: dose is decreased every other day by 5 mg (3 x 2 droplets) Safety follow-up: 4 weeks after end of treatment

Also known as: BX-1

Dronabinol

Placebo in Oral Dosage Form DRUG

Titration period for 4 weeks: titration according to tolerability from 3 x 1 droplet up to 3 x 12 droplets per day; dose increased by 3 x 1 droplet every other day Maintenance period for 12 weeks: individually tolerated maximum dose (up to 3 x 12 droplets) at end of titration period will be continued for maintenance treatment Tapering period for 2 weeks: dose is decreased every other day by 3 x 2 droplets Safety follow-up: 4 weeks after end of treatment

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Arbeitsgemeinschaft medikamentoese Tumortherapie: lead
• Medical University of Graz: collaborator
• Unidata Geodesign: collaborator
• Bionorica SE: collaborator

Study Sites (11)

IIIrd Medical Department, Private Medical University Hospital Salzburg

Salzburg, Salzburg, 5020, Austria

Location

Klinikum Wels-Grieskirchen GmbH, Abteilung für Innere Medizin IV

Wels, Upper Austria, 4600, Austria

Location

Hanusch Krankenhaus der Wiener Gebietskrankenkasse

Vienna, Vienna, 1140, Austria

Location

KABEG-Klinikum Klagenfurt am Woerthersee, Abteilung f. Anaesthesie u. Intensivmedizin

Klagenfurt, 9020, Austria

Location

LKH Hochsteiermark - Standort Leoben Abteilung für Innere Medizin und Hämatologie und internistische Onkologie

Leoben, 8700, Austria

Location

Krankenhaus d. Barmherzigen Brüder, Abt. f. Innere Medizin

Sankt Veit an der Glan, 9300, Austria

Location

Pyhrn-Eisenwurzen Klinikum Steyr, Interne Medizin II

Steyr, A-4400, Austria

Location

KH Zams, Innere Medizin, Internistische Onkologie u. Haematologie

Zams, 6511, Austria

Location

Universitätsmedizin Göttingen Abt. f. Gastroenterologie, gastrointestinale Onkologie u. Endokrinologie

Göttingen, 37075, Germany

Location

München Klinik Neuperlach

München, 81737, Germany

Location

Marienhospital Onkologie, Hämatologie, Palliativmedizin

Stuttgart, 07199, Germany

Location

Related Publications (5)

• van Amerongen G, Kanhai K, Baakman AC, Heuberger J, Klaassen E, Beumer TL, Strijers RLM, Killestein J, van Gerven J, Cohen A, Groeneveld GJ. Effects on Spasticity and Neuropathic Pain of an Oral Formulation of Delta9-tetrahydrocannabinol in Patients WithProgressive Multiple Sclerosis. Clin Ther. 2018 Sep;40(9):1467-1482. doi: 10.1016/j.clinthera.2017.01.016. Epub 2017 Feb 9.

  PMID: 28189366 BACKGROUND

• Davis MP. Cannabinoids for Symptom Management and Cancer Therapy: The Evidence. J Natl Compr Canc Netw. 2016 Jul;14(7):915-22. doi: 10.6004/jnccn.2016.0094.

  PMID: 27407130 BACKGROUND

• Cannabis-In-Cachexia-Study-Group; Strasser F, Luftner D, Possinger K, Ernst G, Ruhstaller T, Meissner W, Ko YD, Schnelle M, Reif M, Cerny T. Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J Clin Oncol. 2006 Jul 20;24(21):3394-400. doi: 10.1200/JCO.2005.05.1847.

  PMID: 16849753 BACKGROUND

• Turgeman I, Bar-Sela G. Cannabis Use in Palliative Oncology: A Review of the Evidence for Popular Indications. Isr Med Assoc J. 2017 Feb;19(2):85-88.

  PMID: 28457056 BACKGROUND

• Jatoi A, Windschitl HE, Loprinzi CL, Sloan JA, Dakhil SR, Mailliard JA, Pundaleeka S, Kardinal CG, Fitch TR, Krook JE, Novotny PJ, Christensen B. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol. 2002 Jan 15;20(2):567-73. doi: 10.1200/JCO.2002.20.2.567.

  PMID: 11786587 BACKGROUND

Related Links

• Sponsor

MeSH Terms

Conditions

Vomiting; Pancreatic Neoplasms

Interventions

Dronabinol; Dosage Forms

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals; Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Study Officials

• Felix Keil, Prof.MD

  Med. Dept. III, Hematolog and Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2019
• First Posted: June 12, 2019
• Study Start: December 16, 2019
• Primary Completion: September 25, 2024
• Study Completion: September 25, 2024
• Last Updated: April 10, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (8); DE (3)