Phase II Study of Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma
Patients with advanced pancreas adenocarcinoma will be randomized on a 6:1 basis to receive standard of care chemotherapy followed by adaptive stereotactic body radiotherapy (SBRT) with concurrent and adjuvant FAK inhibitor defactinib (experimental arm) or standard of care chemotherapy followed by SBRT (control arm). Patients enrolled to the experimental arm will be assessed for clinical outcomes such as progression free survival (PFS), local control, distant control, and toxicity. The first 6 patients randomized to the experimental arm will be considered the safety lead-in and will be assessed for dose-limiting toxicities (DLTs). The 6 patients randomized to the control arm will be evaluated for correlatives but will not be included in the analysis for primary and secondary endpoints.
• Histologically or cytologically confirmed locally advanced pancreas adenocarcinoma that is considered borderline resectable or unresectable per institutional standardized criteria of unresectability or medical inoperability (NCCN guidelines 2.2021 PANC-C 1 of 2).
• Patients with locoregional adenopathy are eligible as long as all suspicious lymph nodes are deemed to be adjacent to the primary tumor as per radiation oncologist assessment.
• At least 3 months of systemic chemotherapy for this disease without progression of local or systemic disease. Newly diagnosed patients may be screened for enrollment in this study and can be enrolled once they have completed 3 months of systemic chemotherapy (and still meet all eligibility criteria) prior to the start of study treatment.
• At least 18 years of age.
• ECOG performance status ≤ 1
• Life expectancy \> 3 months
• Normal bone marrow and organ function within 21 days of randomization as defined below:
‣ Absolute neutrophil count ≥ 1,500/mcL
⁃ Platelets ≥ 100,000/mcL
⁃ Hemoglobin ≥ 9.0 g/dL
⁃ Total bilirubin ≤ 1.5 x IULN; no prior history of Gilbert's syndrome
⁃ AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN or ≤ 5.0 x IULN if due to liver involvement by tumor
⁃ Creatinine clearance ≤ 1.5 x IULN or glomerular filtration rate of ≥ 60 mL/min
⁃ INR ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
⁃ aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
⁃ Albumin ≥ 2.5 mg/dL
• Corrected QT interval (QTc) \< 480 ms (as calculated by the Fridericia correction formula).
• The effects of defactinib on the developing human fetus are unknown. For this reason and because radiation therapy is known to be teratogenic, women of childbearing potential and men must agree to use highly effective contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 120 days after completion of the study
• Ability to understand and willingness to sign an IRB approved written informed consent document