Gemcitabine and Capecitabine With or Without T-ChOS as Adjuvant Therapy for Patients With Resected Pancreatic Cancer

A Single Center, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Gemcitabine (GEM) and Capecitabine (CAP) With or Without T-ChOS as Adjuvant Therapy in Patients With Surgically Resected Pancreatic Cancer.

This is a single center, randomized, double-blind, placebo-controlled phase II trial that will compare the efficacy of T-ChOS in combination with gemcitabine to gemcitabine alone as adjuvant treatment for 6 months in patients with surgically resected pancreatic adenocarcinoma.

Inclusion Criteria:

1. Signed informed consent

2. Histologically confirmed resected ductal pancreatic adenocarcinoma with macroscopic complete resection (R0 and R1). Subjects with neuroendocrine (and mixed type) tumors are excluded

3. Subject should be able to start treatment no later than 12 weeks post-surgery

4. Male or non-pregnant, non-lactating females who are ≥18 years of age at the time of signing the informed consent form (ICF)

5. ECOG/WHO Performance Status (PS) 0-1

6. Females of child-bearing potential (defined as a sexually mature woman who (1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or (2) has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must:

   • Agree to the use of two physician-approved contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study IP; and for 3months following the last dose of IP
   • Has negative serum pregnancy test (β-hCG) result at screening

7. Male subjects:

   • Must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following IP discontinuation, even if he has undergone a successful vasectomy

8. Understand and voluntarily sign an ICF prior to any study related assessments or procedures being conducted

9. Be able to adhere to the study visit schedule and other protocol requirements

10. Acceptable hematology parameters defined as:

    • Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
    • Platelet count ≥ 100 x 10⁹/L
    • Haemoglobin ≥ 5.6 mmol/L

11. Acceptable liver function defined as:

    • Serum bilirubin < 1.5 x upper limit of normal (ULN)
    • ASAT/ALAT < 2.5 x ULN

12. Acceptable renal function with a creatinine clearance ≥ 50 mL/min/ (e.g., using the Cockroft-Gault formula)

Exclusion Criteria:

1. Prior neo-adjuvant treatment, radiation therapy, or systemic therapy for pancreatic adenocarcinoma

2. Presence of or history of metastatic or locally recurrent pancreatic adenocarcinoma

3. Other malignancies, except adequately treated basal carcinoma or squamous cell carcinoma of the skin or in situ cervix carcinoma or incidental prostate cancer (T1a, Gleason score ≤ 6, PSA < 0.5 ng/ml), or any other tumor with a DSF survival of ≥ 5 years

4. History of serious or concurrent illness or uncontrolled medical disorder; any medical condition that might be aggravated by chemotherapy treatment or which could not be controlled; including, but not restricted to:

   • Active infection requiring antibiotics within 2 weeks before the study inclusion
   • Concurrent congestive heart failure NYHA class III - IV
   • Unstable angina pectoris, or myocardial infarction within 6 months and/or prior poorly controlled hypertension
   • History of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies
   • Concomitant use of immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications

5. Known or suspected allergy to the investigational agents or any agents given in association with this trial

6. Any psychological, familial, sociological, or geographical condition which does not permit protocol compliance and medical follow-up

7. Enrollment in any other clinical protocol or investigational study with an interventional agent or assessments that may interfere with study procedures

8. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study

9. Any condition that confounds the ability to interpret data from the study

10. Unwillingness or inability to comply with study procedures

11. Current use of anticoagulation therapy such as heparins both unfractionated and low molecular weighted