An early safety study testing a drug combination given before possible surgery for people with pancreatic cancer that can’t be easily removed yet or hasn’t spread far

Inclusion criteria:
1. Age ≥18 years old.
2. Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
4. Histologically or cytologically confirmed PDAC that is confined to the pancreas.
5. Borderline resectable (surgical resection possible but challenging) or locally advanced (surgical resection not possible) PDAC, as determined by the local investigator based on local institutional guidelines.
6. Measurable tumor lesions according to RECIST v1.1 (within 90 days prior to first dose of study treatment).
7. Have not received prior anticancer therapy for pancreatic cancer.
8. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
9. Agreement to practice effective contraception for female participants of child-bearing potential and non-sterile males. Female participants of child-bearing potential must agree to use effective contraception for up to 7 months after completion of therapy, and nonsterile male participants must agree to use a condom for up to 7 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), orals, injectables, two forms of barrier methods (e.g., condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and hormonal therapy.

Exclusion criteria:
1. Resectable PDAC, meeting the following criteria upon CT/MRI:
1.1. No superior mesenteric vein (SMV) or portal vein (PV) distortion; and
1.2. Clear fat planes around superior mesenteric artery (SMA), celiac artery (CA), and common hepatic artery (CHA).
2. Participants for whom an operation is not considered in the participant’s best interest (eg, due to comorbidity).
3. Histologically or cytologically confirmed pancreatic tumor that is not adenocarcinoma.
4. CA19-9 > 1,000 U/mL.
5. QTc interval using Fridericia's formula (QTcF) > 470 ms.
6. If participants have had major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
7. Have received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed.
8. Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
9. Inadequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to baseline:
9.1. Absolute neutrophil count (ANC) < 1,500 cells/μL without granulocyte colonystimulating factor support
9.2. Lymphocyte count < 500/μL
9.3. Platelet count < 100,000/μL without transfusion
9.4. Hemoglobin < 8.0 g/dL
Note: Participants may be transfused to meet this criterion.
9.5. International Normalized Ratio (INR) or aPTT activated partial thromboplastin time (aPTT) < 1.5 × upper limit of normal (ULN)
Note: This applies only to participants who are not receiving therapeutic anticoagulation; participants receiving therapeutic anticoagulation should be on a stable dose.
9.6. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase > 2.5 × ULN, with the following exception:
Participants with documented liver metastases: AST and/or ALT > 5 × ULN.
9.7. Serum bilirubin ≤ 3 × ULN
9.8. Creatinine clearance ≤ 60 mL/min (calculated using the Cockcroft-Gault formula).
9.9. Serum albumin ≤ 3.0 g/dL.
9.10. Urine dipstick for proteinuria > 2+ (within 7 days prior to initiation of study treatment). Participants with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate < 1 g of protein in 24 hours.
10. Significant cardiovascular disease (such as New York Heart Association cardiac disease
class II or greater), myocardial infarction within 3 months prior to baseline, unstable arrhythmias, or unstable angina.
11. Severe infections at the time of enrollment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
12. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Participants receiving prophylactic antibiotics (eg, to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
13. Prior allogeneic bone marrow transplantation or solid organ transplant.
14. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk for treatment complications.
15. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
16. Treatment with systemic immunosuppressive medications (including, but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to initiation of study treatment, or anticipation of the need for systemic immunosuppressive medication during study treatment, with the following exceptions:
16.1. Participants who have received acute, low-dose, systemic immunosuppressant medications (eg, a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the Medical Monitor.
16.2. The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (eg, fludrocortisone) for participants with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
17. Participation in an investigational drug study or history of receiving any investigational treatment within 30 days prior to the start of treatment on this study.
18. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
19. Pregnant and nursing women.

• US trials at ordinary hospitals: routine care is billed

  In the US a sponsor funds the study drug and study-specific scans, but the routine care around them is billed to insurance. Without US cover that bill falls on you.

  Cost is documented as the barrier that stops roughly 45 percent of US patients joining trials, before any question of being a non-resident. Eligibility on paper does not make a US site reachable. One email to the study coordinator asking what a non-resident without US insurance would be billed settles it either way.

  Verify with: The study coordinator listed on the registry record

  Ask first; potentially very high

• UK access: residence, not citizenship

  Being a British citizen does not by itself entitle you to free NHS treatment; entitlement runs on being ordinarily resident in the UK.

  The UK and EU agreed to continue a planned-treatment scheme equivalent to S2 from 1 January 2021, so an S2 issued by an EU insurer is the thing to ask about for a UK trial. Put the question to both your insurer and the trial coordinator, since sponsors sometimes cover trial-related care regardless.

  Verify with: NHS: planned treatment abroad and the S2 route

  Ask both; not free by citizenship

• Free patient navigation

  myTomorrows (Amsterdam) provides medically trained, multilingual patient navigators who search ClinicalTrials.gov, EU CTIS and ISRCTN and can support a doctor through an expanded-access application. Free to patients and families.

  A navigator keeps searching after any single page stops being current. Use it alongside this site, not instead of your oncologist.

  Verify with: myTomorrows for patients

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