metastatic pancreatic cancer metastatic pancreatic ductal adenocarcinoma
Conditions
Interventions
All included patients will receive combination therapy with rintatolimod and
durvalumab. Patients will start with rintatolimod 200mg via IV infusion twice
per week for a total of 6 weeks (12 doses).
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Histologically or cytologically (Bethesda 5 or 6) confirmed metastatic pancreatic cancer, as indicated by a definite cytology/histology report. • Stable disease according to RECIST criteria version 1.1 after at least 8 cycles of chemotherapy (FOLFIRINOX). • Inclusion = 18 years at time of study entry. • Body weight >30 kg. • WHO performance status of 0-1. • Adequate renal function (eGFR > 40 ml/min). • Adequate liver tests (bilirubin 3.0 x 109/L, platelets > 75 x 109/L , absolute neutrophil count (ANC) >=1.0 × 109 /L and hemoglobin > 5.6 mmol/L. • Effective contraceptive methods. • Patient must have a life expectancy of at least 12 weeks. • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., European Union Data Privacy Directive) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
Exclusion criteria
Exclusion criteria: • Child-Pugh Classification grade B/C. • Current treatment with immunotherapeutic drugs. • Previous malignancy (excluding non-melanoma skin cancer, pancreatic neuroendocrine tumor (pNET) <2cm, and gastrointestinal stromal tumor (GIST) <2cm), unless no evidence of disease and diagnosed more than 3 years before diagnosis of pancreatic cancer, or with a life expectancy of more than 5 years from date of inclusion. • Malignant ascites or pleural effusion. • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy. • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. • An active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or other immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion: A. Patients with vitiligo or alopecia; B. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; C. Any chronic skin condition that does not require systemic therapy; D. Patients without active disease in the last 5 years may be included but only after consultation with the study physician; E. Patients with celiac disease controlled by diet alone. • Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the planned first dose of the study. The following are exceptions to this criterion: 1) Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), 2) Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent and 3) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP. • Prior randomisation or treatment in a previous durvalumab clinical study regardless of treatment arm assignment. • Participation in another clinical study with an investigational product during the last 3 months. • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study. • Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) <=28 days prior to the first dose of s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of the safety run-in (phase Ib) is to determine safety of combination therapy with durvalumab and rintatolimod. The primary objective of the phase II trial is to determine the clinical benefit rate of combination therapy with durvalumab and rintatolimod. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objectives are: 1. To explore the immunogenic effect of combination therapy on the circulating immune profile. 2. To explore the immunogenic effect of combination therapy on the infiltrating immune profile. 3. To determine the clinical effect of combination therapy on survival rates 4. To determine the clinical effect of combination therapy on quality of life. | — |
Countries
Netherlands
Outcome results
None listed