Trial of Radiotherapy in Combination with TTI-101 in Patients with Borderline Resectable Pancreatic Cancer

University of Colorado Denver (CU Denver)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Pancreatic Cancer

Treatments: Drug: TTI-101

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06141031

22-0734.cc

Details and patient eligibility

About

To evaluate the safety, tolerability, and efficacy of TTI-101 given in combination with Stereotactic Body Radiation Therapy (SBRT) in borderline resectable pancreatic ductal adenocarcinoma.

Enrollment: 35 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients must have pathologically confirmed pancreatic adenocarcinoma with borderline resectable PDAC as defined by NCCN guidelines, with no expected arterial resection-reconstruction.
• Age ≥ 18 years at time of study entry.
• Provision to sign and date the consent form.
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Ability to swallow tablets by mouth.
• ECOG performance status ≤2 or KPS ≥60%
• Absolute neutrophil count ≥ 1,000/mcL
• Platelets ≥ 70,000/mcL
• Hemoglobin ≥ 9 g/dL, patients may be transfused to meet this criterion
• Serum albumin ≥ 2.8 g/dL
• Total Bilirubin ≤ 2mg/dL
• AST(SGOT)/ALT(SGPT)/ALP ≤ 3 x institutional upper limit of normal (IULN)
• Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL >40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:

Males:

Creatinine CL (mL/min) = Weight (kg) x (140 - Age) / 72 x serum creatinine (mg/dL)

Females:

Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 / 72 x serum creatinine (mg/dL)

• 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
• Sexually active women of childbearing potential (defined in section 7.1) and men must agree to use at least 1 highly effective method of contraception (defined in section 7.1) from screening and for at least 30 days after administration of the last dose of the study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

Exclusion criteria

• Pregnant or breastfeeding. Patient must have a negative serum or urine pregnancy test within 5 days of study treatment.
• Previous treatment of the current malignancy with a STAT inhibitor.
• Herbal preparations are not allowed throughout the study. These herbal medications include but are not limited to St. John's wort, kava, ephedra (Ma Huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Participants should stop using herbal medications 7 days prior to the first dose of study treatment.
• Senna and flaxseed are permitted.
• Is not fully recovered from all COVID-19-related symptoms for 2 weeks prior to Cycle 1 Day 1, if previously tested positive for COVID-19.
• Ongoing toxicity (except alopecia) due to a prior therapy, unless returned to baseline or Grade 1 or less.
• Has had major surgery within 3 weeks prior to starting IP or has not recovered from major side effects due to surgery.
• Significantly impaired cardiac function such as unstable angina pectoris, symptomatic congestive heart failure with New York Heart Association Class III or IV, myocardial infarction within the last 12 months prior to study entry; serious arrhythmia (including QTc prolongation of >470 ms and/or pacemaker) or prior diagnosis of congenital long QT syndrome.
• Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters for control of effusions or ascites are allowed.
• History of cerebrovascular accident or stroke within the previous 2 years.
• History of hepatic encephalopathy.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12 mg/dL, or corrected serum calcium >ULN).
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
• History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition as TTI- 101 (hydroxyl-naphthalene sulfonamides).
• Known active metastases in the central nervous system (unless stable by brain imaging studies for at least 1 month without evidence of cerebral edema and no requirements for corticosteroids or anticonvulsants).
• History of malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the IP.
• Participants with chronic HBV infection, unless screening viral load <500 IU/mL on stable doses of antiviral therapy.

Note: Participants with chronic HCV infection are allowed to enroll into the study but do not have a defined maximum viral load requirement for study entry. Participants with both HBV and HCV infection are excluded unless they have negative HCV RNA.

• History of malignancy other than PDAC within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (eg, 5-year overall survival [OS] rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.

• Has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate participation in the clinical study, or compromise compliance with the protocol such as:

  • Chronic pancreatitis.
  • Active untreated or uncontrolled fungal, bacterial, or viral infections (including COVID-19), sepsis, etc.
  • Acute and chronic, active infectious disorders including viral and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy.

• Prior treatment for pancreatic cancer in the past 2 years and outside of the induction chemotherapy received for the current diagnosis.

• Measurable distant metastases on re-staging imaging post chemotherapy that meets RECIST1.1 criteria.

• Currently receiving any other investigational agents or has participated in a study of an investigational agent or using an investigational device overlapping with study treatments within 3-6 months preceding diagnosis at the discretion of the PI.

• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to TTI-101.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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35 participants in 2 patient groups

Phase I

Experimental group

Description:

During Phase 1, up to 2 dose levels of TTI-101 with SBRT will be tested using a 3 + 3 dose-escalation design to determine the RP2D. Up to 3 participants may be enrolled with either 0/3 or 1/3 DLT in order to more fully evaluate the safety and tolerability at a given dose level. Therefore, a minimum of 9 patients (3 at dose 0, and 6 at dose 1) and maximum 18 (6 patients at each dose level) will be enrolled in the phase 1.

Treatment:

Drug: TTI-101

Phase II

Experimental group

Description:

An additional 12 patients will be enrolled in phase 2 so that total of 18 patients are treated at RP2D in phase 2 (the 6 patients treated at RP2D in phase 1 will be rolled over to phase 2) of TTI-101 in combination with SBRT.

Treatment:

Drug: TTI-101