Phase I/IB Trial of Radiotherapy in Combination With TTI-101 in Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma
The survival rate for patients with pancreatic cancer remains at a dismal 10% or less at 5 years, and although trials integrating stereotactic body radiation therapy (SBRT) alone have shown improvement in local control, initial invigoration of immune response, and relief of symptom burden, SBRT has not demonstrated any improvement in survival. Preclinical research has established that STAT3 inhibition given concurrently with SBRT and in the maintenance phase acts as a synergistic agent that enhances the pro-inflammatory effects of SBRT while reducing its undesired effects (including fibrosis and immunosuppression). This study exploits the window of opportunity post-chemotherapy to advance the hypothesis that the addition of STAT3 inhibition in combination with SBRT will be safe and will enhance 2-year progression-free survival.
• Pathologically confirmed pancreatic adenocarcinoma that is borderline resectable or locally advanced as defined by NCCN guidelines, with no expected arterial resection/reconstruction.
• Patients who are borderline resectable must have completed standard of care induction chemotherapy between 1 and 3 weeks prior to planned start of TTI-101 + SBRT. Patients who exceed this window may be considered for enrollment if they complete an additional cycle of induction chemotherapy prior to initiation of study treatment (per provider discretion). The amount of induction chemotherapy cycles allowed will be left to the discretion of the treating medical oncologist. There is no timing restriction for patients with locally advanced disease.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Adequate bone marrow and organ function as defined below:
‣ Absolute neutrophil count ≥ 1.0 K/cumm
⁃ Platelets ≥ 70 K/cumm
⁃ Hemoglobin ≥ 9.0 g/dL (patients may be transfused to meet this criterion)
⁃ Total bilirubin ≤ 2 mg/dL
⁃ AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
⁃ Serum albumin ≥ 2.8 g/dL
⁃ Ionized calcium ≤ 1.5 mmol/L, calcium ≤ 12 mg/dL, or corrected serum calcium ≤ IULN)
⁃ Measured creatinine clearance \> 40 mL/min or calculated creatinine clearance \> 40 mL/min by Cockcroft-Gault or by 24-hour urine collection for determination of creatinine clearance (calculations in protocol).
• Able to swallow pills.
• INR and aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy (in which case INR and PTT must be within therapeutic range of intended use of anticoagulants)
• The effects of TTI-101 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use at least 1 highly effective method of contraception from screening through the duration of study participation, and for 30 days after last dose of TTI-101. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform the treating physician immediately.
• Agreement to adhere to Lifestyle Considerations throughout study duration.
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.