Phase II Pilot Study of Digitoxin Combined with Chemotherapy in Patients with Inoperable Pancreatic Adenocarcinoma

Trial ID: 2024-512128-12-01
Protocol: Digi-Panc-1
Sponsor: Vaestra Goetalandsregionen

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Diseases & Conditions

Pancreatic carcinoma

Objectives

The primary objective of this trial is to improve the survival of patients with inoperable **pancreatic adenocarcinoma**. This is clinically significant as pancreatic cancer is often diagnosed at an advanced stage, and improving survival rates is a critical goal in the management of this disease.

Secondary objectives include:

Evaluating the effectiveness of chemotherapy and **digitoxin** in both intention-to-treat (ITT) and per protocol (PP) treated populations.
Assessing the safety and tolerability of the treatment regimens.
Conducting life quality assessments to understand the impact of the treatment on patients' quality of life.
Performing translational studies, specifically analyzing cytokines at baseline and at 3 months, to gain insights into the biological effects of the treatment.

Participants

The clinical trial focuses on patients diagnosed with **pancreatic cancer**, specifically inoperable pancreatic adenocarcinoma. The study population includes both male and female participants aged 18 years and older. Participants are required to have a WHO performance status of 0-2 and must have histologically or cytologically confirmed inoperable adenocarcinoma of the pancreas. The trial does not include a vulnerable population. Participants must be newly diagnosed and have not commenced any other treatment for pancreatic cancer. They should have radiographically measurable or evaluable disease according to RECIST (v1.1) criteria. The trial requires participants to be capable of managing their medication independently and to have provided written consent to participate. Female participants of childbearing potential must have a negative pregnancy test prior to treatment and agree to use adequate contraception during the study and for six months after the last dose. Male participants with partners of childbearing potential must also agree to use adequate contraception. The sponsor has not provided information regarding the total number of participants in the trial.

Plans and Procedures

The clinical trial is a **prospective single-arm pilot phase II trial** designed to evaluate the efficacy of **digitoxin** in combination with chemotherapy for patients with inoperable **pancreatic cancer**. The primary objective is to improve the survival of patients with inoperable pancreatic adenocarcinoma. The trial will assess progression-free survival at one year as the primary endpoint, with secondary endpoints including overall survival, objective response rate, safety, and quality of life assessments. The trial is expected to commence recruitment on December 1, 2024, and conclude by October 1, 2027.

Participants will be required to attend several study visits throughout the trial. The initial visit will be a screening visit to confirm eligibility based on criteria such as age, performance status, and disease confirmation. Following successful screening, participants will begin treatment with **digitoxin** tablets, administered orally. Follow-up visits will occur at regular intervals to monitor disease progression, assess treatment safety, and evaluate biochemical responses. These visits will include radiographic assessments and laboratory tests to measure tumor markers and cytokines pivotal for cancer and inflammation. The end-of-study visit will occur at the conclusion of the treatment period or upon early termination.

The expected duration of participant involvement is up to 52 weeks, corresponding to the maximum treatment period. Participants may be withdrawn from the study early if they experience unacceptable adverse events, disease progression, or if they withdraw consent. The trial is not categorized as low intervention and is conducted under controlled conditions to ensure the reliability of the results. The study is designed to provide valuable insights into the potential benefits of **digitoxin** in treating inoperable pancreatic cancer, with a focus on improving patient outcomes and quality of life.

Treatment

The clinical trial involves the administration of **Digitoxin**, a cardiac glycoside, as the experimental medication. The pharmaceutical form of the medication is a **tablet**, specifically marketed under the name "Digitoxin AWD 0,07 0,07 mg/Tablette" by TEVA GMBH. Each tablet contains 0.07 mg of **digitoxin** as the active substance. The medication is administered **orally**. The maximum daily dose is 0.28 mg, with a total maximum dose of 1456 mg over the course of the treatment. The treatment period is set for a maximum of 52 weeks. The **digitoxin** used in this trial is of chemical origin, and the product is not a paediatric formulation.

In this study, **digitoxin** is being evaluated in combination with standard chemotherapy for patients with inoperable pancreatic adenocarcinoma. The trial is designed as a prospective single-arm pilot phase II study, with the primary objective of improving patient survival. No placebo or comparator treatment is used in this trial. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed regimen.

Efficacy

Efficacy in the clinical trial titled "Digi-Panc-1; A prospective single-arm pilot phase II trial of digitoxin in combination with chemotherapy for patients with inoperable pancreatic cancer" will be assessed using several primary and secondary endpoints. The primary endpoint is **progression-free survival** at 1 year, measured from the date of enrollment, which marks the start of digitoxin tablet administration. Secondary endpoints include overall survival at 1 year, progression-free survival defined as the time from enrollment until the earliest date of disease progression, and objective response rate and duration of response, all determined by radiographic disease assessments per RECIST (v1.1).

Additional secondary endpoints involve the safety and tolerability of the treatment regimens, assessed through adverse events and changes in safety assessments, including laboratory parameters. Biochemical response will be evaluated by changes in serum tumor markers (CA19-9, CEA, CA125) with baseline measurements taken before the start of digitoxin tablets and subsequent evaluations every 3 months. Quality of life will be assessed using the EORTC QLQ-C30 and EORTC QLQ-PAN-26 instruments. Translational studies will analyze cytokines pivotal for cancer and inflammation, with more than 40 cytokines examined before the start of digitoxin and at 3 months of treatment.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Male or female, 18 years or older.
WHO performance status 0-2.
Histologically or cytologically confirmed inoperable adenocarcinoma of the pancreas. Histologically or cytologically confirmed from primary tumor in the pancreas or metastasis.
The patient shall be newly diagnosed and not have started any other treatment for the pancreatic cancer.
Radiographically measurable or evaluable disease, according RECIST (v1.1).
The patient is able to take care of his/her medication.
The patient has given written consent to participate in the trial.
Female patient of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Female patients of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 6 months after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
Male patients with a female partner of childbearing potential must agree to use an adequate method of contraception (condom and acceptable contraception method for the partner), starting with the first dose of study therapy through 6 months after the last dose of study therapy. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

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Exclusion Criteria

Chronic or current active infectious disease requiring systemic antibiotics, antifungal or antiviral treatment.
Significant concurrent, uncontrolled medical condition including, but not limited: to renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral, or psychiatric disease.
Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from day 1 of trial drug administration. Patients with heart disease already on a cardiac glycoside are not eligible.
Cardiac arrythmia which may worsen by digitoxin therapy.
Current or previous other malignancy within 2 years of trial entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other non-invasive or indolent malignancy.
Patient who has already been subjected to or started chemotherapy or other treatment for the pancreatic cancer.
Absolute B-neutrophil count (ANC) <1.5 × 10^9/L.
B-Platelets < 75 × 10^9/L.
B-Haemoglobin < 9 g/L (transfusions are permitted to achieve baseline haemoglobin level).
P-ALAT/ASAT > 2.5 × ULN; or > 5 × ULN in the presence of liver metastases.
Total P-bilirubin > 1.5 × ULN (use of biliary stent to achieve bilirubin levels is permitted).
S- LDH > 3 × ULN in the absence of haemolysis.
P-Potassium < 3.5 or > 4.5 mmol/L.
P-Sodium <137 or >145 mmol/L
P-Albumin <25 g/L
P-Calcium < 2.15 or > 2.50 mmol/L.
S-Magnesium <0.7 mmol/L or > 1.1 mmol/L
S-creatinine > 150 μmol/L.
Pregnancy or female patients that are breastfeeding and not willing to refrain.
Hypersensitivity to digitoxin or other cardiac glycoside or any other ingredients in the tablets (see SmPC).
Carotid sinus syndrome.
Simultaneous administration of intravenous calcium salts.
Thoracic aortic aneurysm.
Intended electrical cardioversion.