Neoadjuvant Folfirinox Combined With Pembrolizumab Followed by Surgery for Patients With Resectable Pancreatic Cancer

• Status: Not yet recruiting
• Trial end date: 2024-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Abbreviated Title: Neoadjuvant FOLFIRINOX combined with Pembrolizumab followed by surgery for patients with resectable pancreatic cancer Trial Phase: Phase II Clinical Indication: Pancreatic ductal adenocarcinoma; Adenocarcinoma; AJCC I, II, or III; 1st Line neoadjuvant Trial Type: Interventional prospective Type of control: Historical Route of administration: IV Treatment Groups: Neoadjuvant FOLFIRINOX combined with Pembrolizumab followed by surgery for patients with resectable pancreatic cancer Number of trial participants: 27 Estimated enrollment period: 24 months Estimated duration of trial: 3.5 Years Duration of Participation: 9 months Estimated average length of treatment per patient: 9 months

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Folfirinox; Pembrolizumab

Criteria

Inclusion Criteria:

1. Patient is ≥18 years of age and has histologically or cytologically confirmed localized adenocarcinoma of the pancreas that is potentially resectable. Patients with islet cell or other neuroendocrine neoplasms are excluded.

2. Definition of localized, potentially resectable disease:

1. Staging by intravenous contrast-enhanced thin section helical abdominal computed tomography (2.5 mm cuts or less) or MRI (for patients with an IV contrast allergy) using pancreatic protocol. Endoscopic ultrasound is required for tissue acquisition and staging confirmation.

2. No extension to superior mesenteric artery (SMA) and hepatic artery. Patent superior mesenteric vein/portal vein (SMV/PV) with < 180-degree abutment and no evidence of invasion.

3. Clear fat plane between the SMA and celiac axis.

4. No extension to celiac axis and hepatic artery.

5. Patent superior mesenteric vein and portal vein.

6. No evidence of distant disease by additional imaging of the chest (CT with or without contrast or PET/CT) and pelvis (CT with contrast, PET/CT, or MRI with contrast).

7. No other evidence of distant disease 3. If a female patient is of childbearing potential, she must have a negative serum pregnancy test (β hCG) documented within 72 hours of the first administration of study drug.

4. If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator.

5. Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least [X days/weeks, corresponding to time needed to eliminate any study treatment(s) (e.g. 5 terminal half-lives for pembrolizumab and/or any active comparator/combination) plus an additional 90 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose] after the last dose of study treatment and refrain from donating sperm during this period.

6. Patient must not have received prior chemotherapy or radiation for pancreatic cancer.

7. Patient has an ECOG performance status PS 0-1. 8. Patient has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form prior to participation in any study-related activities.

9. A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:

a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least [X days/weeks (corresponding to time needed to eliminate any study treatment(s) (pembrolizumab and/or any active comparator/combination) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity] after the last dose of study treatment.

10. Have adequate organ function as defined in the following table (Table 4). Specimens must be collected within 10 days prior to the start of study intervention.

Hematological Absolute neutrophil count (ANC) ≥1500/μL Platelets ≥100 000/μL Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La Renal Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) Coagulation International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

Exclusion Criteria:

1. Patient has borderline resectable, locally advanced unresectable or advanced metastatic disease. Patients with neuroendocrine tumors, adenosquamous cancer, lymphoma of the pancreas, or ampullary cancer are also ineligible.

2. Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.

3. Patient has known infection with HIV.

4. Patient has undergone major surgery, other than diagnostic surgery (-e.g. diagnostic laparoscopy or placement of a central venous catheter), within 4 weeks prior to Day 1 of treatment in this study.

5. Patient has a history of allergy or hypersensitivity to the study drugs.

6. Patient has serious medical risk factors involving any of the major organ systems such that the Investigator considers it unsafe for the patient to receive chemotherapy and/or radiation therapy.

7. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.

8. Patient has had clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before randomization.

9. Patient is unwilling or unable to comply with study procedures.

10. Patient is enrolled in any other therapeutic clinical protocol or investigational trial.

11. Patients aged ≥ 80 are not excluded. However, candidates in this age group should be thoroughly evaluated before enrollment in the study, to ensure they are fit to receive chemotherapy, and to potentially undergo pancreaticoduodenectomy. In addition to meeting all of the baseline patient selection criteria, clinical judgment on their susceptibility to infection and expected stability of their performance status and suitability to receive intensive chemotherapy cycles, should be paid special attention to. Patients should not be enrolled in the study should there be any hesitation on any of these considerations. Baseline criteria for all patients enrolled on the study must be carefully evaluated and all criteria followed appropriately.

12. Patient has evidence of peripheral neuropathy Grade 2 or higher.

13. Pregnant or lactating women who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.

14. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).

15. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug.

16. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.

17. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

18. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.

19. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

20. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as detectable HCV by RNA) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.

21. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.

22. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

23. Has had an allogenic tissue/solid organ transplant.