Radiotherapy in Combination With TTI-101 in Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma

Conditions

• Pancreatic Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• TTI-101 — DRUG
  Given at the assigned dose assigned in the protocol.
• Stereotactic body radiation therapy — RADIATION
  Given at the assigned dose and fractions assigned in the protocol.

Study Details

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.

Key Dates

Start date

Jan 16, 2024

Status verified

May 2026

Primary completion

Jun 30, 2029

Completion

Jun 30, 2029

Study Design

Enrollment

18 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: TTI-101 + SBRT Dose Level 0 (original starting dose)
  * Treatment consists of TTI-101 by mouth twice daily at 400 mg and SBRT (5 fractions of 6.6 Gy each) over the course of 3 weeks. * After combination therapy is concluded, patients who entered the study as locally advanced will receive up to 10 additional weeks of TTI-101 monotherapy (until a tumor biopsy that will occur between Weeks 9 and 13). After discontinuation of TTI-101, patients will receive SOC chemotherapy as part of their routine care (not dictated by study participation). * Patients who entered the study as borderline resectable will be assessed following the initial 3 weeks of treatment. If they have reverted to resectable, they will undergo surgery, followed by optional adjuvant chemotherapy at the discretion of their treating team. If they are unresectable, they will follow the path of the locally advanced patients (up to 10 weeks of TTI-101 monotherapy, followed by disease assessment, followed by SOC chemotherapy).
• Experimental: TTI-101 + SBRT Dose Level -1 (WUSM starting dose)
  * Treatment consists of TTI-101 by mouth twice daily at 200 mg \& SBRT (3 fractions of 6 Gy each, approximately every other day) over the course of 3 weeks. * After combination therapy is concluded, patients who entered the study as locally advanced will receive up to 10 additional weeks of TTI-101 monotherapy (until a tumor biopsy that will occur between Weeks 9 and 13 if possible). After discontinuation of TTI-101, patients will receive SOC chemotherapy as part of their routine care (not dictated by study participation). * Patients who entered the study as borderline resectable will be assessed following the initial 3 weeks of treatment. If they have reverted to resectable, they will undergo surgery, followed by optional adjuvant chemotherapy at the discretion of their treating team. If they are unresectable, they will follow the path of the locally advanced patients (up to 10 weeks of TTI-101 monotherapy, followed by disease assessment, followed by SOC chemotherapy).
• Experimental: TTI-101 + SBRT Dose Level -2
  * Treatment consists of TTI-101 by mouth twice daily at 200 mg and SBRT (1 fraction of 12 Gy each) over the course of 3 weeks. * After combination therapy is concluded, patients who entered the study as locally advanced will receive up to 10 additional weeks of TTI-101 monotherapy (until a tumor biopsy that will occur between Weeks 9 and 13 if possible). After discontinuation of TTI-101, patients will receive SOC chemotherapy as part of their routine care (not dictated by study participation). * Patients who entered the study as borderline resectable will be assessed following the initial 3 weeks of treatment. If they have reverted to resectable, they will undergo surgery, followed by optional adjuvant chemotherapy at the discretion of their treating team. If they are unresectable, they will follow the path of the locally advanced patients (up to 10 weeks of TTI-101 monotherapy, followed by disease assessment, followed by SOC chemotherapy).
• Experimental: TTI-101 + SBRT Expansion Phase
  * Treatment consists of TTI-101 by mouth twice daily at the RP2D dose and SBRT (at the RP2D dose and timing) over the course of 3 weeks. * After combination therapy is concluded, patients who entered the study as locally advanced will receive up to 10 additional weeks of TTI-101 monotherapy (until a tumor biopsy that will occur between Weeks 9 and 13 if possible). After discontinuation of TTI-101, patients will receive SOC chemotherapy as part of their routine care (not dictated by study participation). * Patients who entered the study as borderline resectable will be assessed following the initial 3 weeks of treatment. If they have reverted to resectable, they will undergo surgery, followed by optional adjuvant chemotherapy at the discretion of their treating team. If they are unresectable, they will follow the path of the locally advanced patients (up to 10 weeks of TTI-101 monotherapy, followed by disease assessment, followed by SOC chemotherapy).

Primary Outcome Measure

Maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of TTI-101 and SBRT [ Time Frame: Through completion of follow-up (estimated to be 2 years and 3 months) ]

Central Contacts

• Sana Karam, M.D., Ph.D.
  314-273-3240
  [email protected]

Locations (2)

Find similar trials in Aurora, CO

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