DURVALUMAB for Metastatic pancreatic cancer

Inclusion criteria

• {"criterion_text":"- Metastatic pancreatic cancer as defined by the presence of radiologically suspect metastatic lesions"}
• {"criterion_text":"- Inclusion ≤ 6 weeks after the start date of the last cycle of FOLFIRINOX (= ≤ 4 weeks after stopping FOLFIRINOX)"}
• {"criterion_text":"- SIII<900 (Systemic Immune-Inflammation Index = ((absolute neutrophil count * platelet count) / absolute lymphocyte count))."}
• {"criterion_text":"- CA 19.9 <1000kU/L"}
• {"criterion_text":"- Age ≥ 18 years at time of study entry."}
• {"criterion_text":"- Body weight >30 kg."}
• {"criterion_text":"- WHO performance status of 0-1."}
• {"criterion_text":"- Adequate renal function (eGFR > 40 ml/min)."}
• {"criterion_text":"- Adequate liver tests (bilirubin ≤ 1.5 times normal; ALAT/ASAT ≤ 5 times normal)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Effective contraceptive methods."}
• {"criterion_text":"- Patient must have a life expectancy of at least 12 weeks."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Stable disease according to RECIST criteria version 1.1 after at least 8 cycles of chemotherapy (FOLFIRINOX)."}

Exclusion criteria

• {"criterion_text":"- Child-Pugh Classification grade B/C."}
• {"criterion_text":"- Prior randomisation or treatment in a previous durvalumab clinical study regardless of treatment arm assignment."}
• {"criterion_text":"- Participation in another clinical study with an investigational product during the last 3 months."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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 study drug If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca and the investigator."}
• {"criterion_text":"- Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. o\tPatients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. o\tPatients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician."}
• {"criterion_text":"- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable."}
• {"criterion_text":"- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug."}
• {"criterion_text":"- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable."}
• {"criterion_text":"- History of allogenic organ transplantation."}
• {"criterion_text":"- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent."}
• {"criterion_text":"- Current treatment with immunotherapeutic drugs."}
• {"criterion_text":"- History of leptomeningeal carcinomatosis."}
• {"criterion_text":"- Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry to rule out the presence of brain metastasis."}
• {"criterion_text":"- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms."}
• {"criterion_text":"- Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Adjust wording as necessary and consider evaluating at screening for studies with known hepatotoxicity or other relevant requirements."}
• {"criterion_text":"- Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice)."}
• {"criterion_text":"- Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Malignant ascites or pleural effusion."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients."}
• {"criterion_text":"- 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.\tPatients with vitiligo or alopecia; B.\tPatients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; C.\tAny chronic skin condition that does not require systemic therapy; D.\tPatients without active disease in the last 5 years may be included but only after consultation with the study physician; E.\tPatients with celiac disease controlled by diet alone."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}

Primary endpoints

• {"endpoint_text":"- Phase Ib The primary endpoint of the safety run-in (phase Ib) is the recommended phase II dose (RP2D) defined by the highest dose per protocol without dose-limiting toxicity (DLT) according to a 3+3 design (see section 8.3.2 and 8.3.7) related to the intervention from the start of rintatolimod until 6 weeks after the first day of the first cycle of durvalumab (one cycle is 28 days).","definition_or_measurement_approach":"RP2D defined as highest dose per protocol without dose-limiting toxicity (DLT) according to a 3+3 dose-escalation design; DLT assessment window from start of rintatolimod until 6 weeks after first day of first durvalumab cycle (one cycle = 28 days)."}
• {"endpoint_text":"- Phase II The primary endpoint of the phase II trial is the clinical benefit rateclinical benefit rate; response is defined as stable disease, partial or complete response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) determined 6 months after start of combination therapy.","definition_or_measurement_approach":"Clinical benefit rate defined as proportion of patients with stable disease, partial response, or complete response per RECIST 1.1 assessed at 6 months after start of combination therapy."}

Secondary endpoints

• {"endpoint_text":"- Overall survival (OS), defined as the time between start combination therapy with durvalumab and rintatolimod to date of death.","definition_or_measurement_approach":"OS measured as time from start of combination therapy to date of death."}
• {"endpoint_text":"- Progression free survival (PFS), defined as the time between start of combination therapy with durvalumab and rintatolimod to date of progression (according to RECIST criteria version 1.1) or death, whichever occurs first.","definition_or_measurement_approach":"PFS measured as time from start of combination therapy to objective progression per RECIST 1.1 or death."}
• {"endpoint_text":"- Immunogenic efficacy defined as >50% increase in circulating Ki67+ CD 8+ T cell in the peripheral blood.","definition_or_measurement_approach":"Immunogenic efficacy assessed by change in circulating Ki67+ CD8+ T cells; endpoint defined as >50% increase from baseline."}
• {"endpoint_text":"- Infiltrating immune profile defines as the change in infiltrating immune profile after start of combination therapy.","definition_or_measurement_approach":"Change in tumour/infiltrating immune profile measured after start of combination therapy (methodology as per protocol; exact assays not detailed in provided JSON)."}
• {"endpoint_text":"- Quality of life (EORTC QLQ-C30), measured at baseline, after 5 weeks, 13 weeks, 25 weeks, 37 weeks, and 49 weeks after start immunotherapy.","definition_or_measurement_approach":"Quality of life assessed using EORTC QLQ-C30 at baseline and at scheduled timepoints: 5, 13, 25, 37, and 49 weeks after start of immunotherapy."}

Netherlands

Earliest CTIS Part Ii Submission Date

01-08-2024

Latest Decision Or Authorization Date

28-05-2025

Processing Time Days

300

Number Of Sites

1

Number Of Participants

43

Primary sponsor

Full Name

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"Erasmus MC","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"AIM Immunotech","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"Astra Zeneca","duties_or_roles":"Source of monetary support","organisation_type":""}