Combining anti-PD-L1 immune checkpoint inhibitor durvalumab with TLR-3 agonist rintatolimod in patients with metastatic pancreatic ductal adenocarcinoma for therapy efficacy. DURIPANC study.
- Conditions
- metastatic pancreatic cancermetastatic pancreatic ductal adenocarcinoma1001567410017991
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 43
• 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 <= 6 weeks after stopping FOLFIRINOX.
• An accessible metastatic lesion for histological tissue collection.
• SIII<900 (Systemic Immune-Inflammation Index = ((absolute neutrophil count *
platelet count) / absolute lymphocyte count)).
• CA 19.9 <1000kU/L.
• Age >= 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 <= 1.5 times normal; ALAT/ASAT <= 5 times
normal).
• Adequate bone marrow function (WBC > 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.
• 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objective of the safety run-in (phase Ib) is to determine safety of<br /><br>combination therapy with durvalumab and rintatolimod.<br /><br>The primary objective of the phase II trial is to determine the clinical<br /><br>benefit rate of combination therapy with durvalumab and rintatolimod. </p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary objectives are:<br /><br>1. To explore the immunogenic effect of combination therapy on the circulating<br /><br>immune profile.<br /><br>2. To explore the immunogenic effect of combination therapy on the infiltrating<br /><br>immune profile.<br /><br>3. To determine the clinical effect of combination therapy on survival rates<br /><br>4. To determine the clinical effect of combination therapy on quality of life.</p><br>