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

NCT ID: NCT03984214

Last Updated: 2025-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-16
• Study Completion Date: 2024-09-25

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.

Detailed Description

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.

In detail, investigators want to study whether dronabinol has a positive influence on quality of life and whether symptoms caused by the tumor or by the chemotherapy itself might be palliated by dronabinol. Beneficial and potential harmful side effects and the personal perception of advanced pancreatic cancer patients will be documented.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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)

Group Type: ACTIVE_COMPARATOR

Dronabinol in Oral Dosage Form

Intervention Type: 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

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

Group Type: PLACEBO_COMPARATOR

Placebo in Oral Dosage Form

Intervention Type: 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

Interventions

Dronabinol in Oral Dosage Form

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

Intervention Type: DRUG

Placebo in Oral Dosage Form

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

Intervention Type: DRUG

Other Intervention Names

BX-1

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Graz

OTHER

Sponsor Role: collaborator

Unidata Geodesign

UNKNOWN

Sponsor Role: collaborator

Bionorica SE

INDUSTRY

Sponsor Role: collaborator

Arbeitsgemeinschaft medikamentoese Tumortherapie

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Felix Keil, Prof.MD

Role: PRINCIPAL_INVESTIGATOR

Med. Dept. III, Hematolog and Oncology

Locations

IIIrd Medical Department, Private Medical University Hospital Salzburg

Salzburg, Salzburg, Austria

Klinikum Wels-Grieskirchen GmbH, Abteilung für Innere Medizin IV

Wels, Upper Austria, Austria

Hanusch Krankenhaus der Wiener Gebietskrankenkasse

Vienna, Vienna, Austria

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

Klagenfurt, , Austria

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

Leoben, , Austria

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

Sankt Veit an der Glan, , Austria

Pyhrn-Eisenwurzen Klinikum Steyr, Interne Medizin II

Steyr, , Austria

KH Zams, Innere Medizin, Internistische Onkologie u. Haematologie

Zams, , Austria

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

Göttingen, , Germany

München Klinik Neuperlach

München, , Germany

Marienhospital Onkologie, Hämatologie, Palliativmedizin

Stuttgart, , Germany

Countries

Austria; Germany

References

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.

Reference Type: BACKGROUND

PMID: 28189366 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27407130 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16849753 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28457056 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11786587 (View on PubMed)

Related Links

http://www.agmt.at

Sponsor

Other Identifiers

AGMT_DISCOVER

Identifier Type: -

Identifier Source: org_study_id