RECRUITING

Phase I/IB Trial of Radiotherapy in Combination With TTI-101 in Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma

Conditions

Pancreatic Cancer borderline resectable locally advanced

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

Phase I/IB Trial of Radiotherapy in Combination With TTI-101 in Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma

Quick Facts

Study Start:2024-01-16

Study Completion:2028-09

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06141031

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Patients must have pathologically confirmed pancreatic adenocarcinoma with borderline resectable or locally advanced PDAC as defined by NCCN guidelines, with no expected arterial resection-reconstruction. 2. Borderline resectable patients only: Completion of inducation chemotherpy within 1-3 weeks of study treatment start. Patients that exceed this window should complete an additional cycle of induction chemotherapy prior to initiation of study treatment, per provider discretion. 3. Age ≥ 18 years at time of study entry. 4. Provision to sign and date the consent form. 5. Stated willingness to comply with all study procedures and be available for the duration of the study. 6. Ability to swallow tablets by mouth. 7. ECOG performance status ≤2 or KPS ≥60% 8. Absolute neutrophil count ≥ 1,000/mcL 9. Platelets ≥ 70,000/mcL 10. Hemoglobin ≥ 9 g/dL, patients may be transfused to meet this criterion 11. Serum albumin ≥ 2.8 g/dL 12. Total Bilirubin ≤ 2mg/dL 13. AST(SGOT)/ALT(SGPT)/ALP ≤ 3 x institutional upper limit of normal (IULN) 14. 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: 15. 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 16. 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 17. 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.	1. Pregnant or breastfeeding. Patients must have a negative serum or urine pregnancy test within 5 days of study treatment. 2. Previous treatment of the current malignancy with a STAT inhibitor. 3. 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. 4. 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. 5. Ongoing toxicity (except alopecia) due to a prior therapy, unless returned to baseline or Grade 1 or less. 6. Has had major surgery within 3 weeks prior to starting IP or has not recovered from major side effects due to surgery. 7. 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. 8. 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. 9. History of cerebrovascular accident or stroke within the previous 2 years. 10. History of hepatic encephalopathy. 11. Uncontrolled or symptomatic hypercalcemia (ionized calcium \>1.5 mmol/L, calcium \>12 mg/dL, or corrected serum calcium \>ULN). 12. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). 13. History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition as TTI-101 (hydroxyl-naphthalene sulfonamides). 14. 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). 15. History of malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the IP. 16. 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. 17. 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. 18. 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. 19. Prior treatment for pancreatic cancer in the past 2 years and outside of the induction chemotherapy received for the current diagnosis. 20. Measurable distant metastases on re-staging imaging post chemotherapy. tCurrently 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. 21. A history of allergic reactions attributed to compounds of similar chemical or biologic composition to TTI-101.

Inclusion Criteria

Exclusion Criteria

1. Patients must have pathologically confirmed pancreatic adenocarcinoma with borderline resectable or locally advanced PDAC as defined by NCCN guidelines, with no expected arterial resection-reconstruction.
2. Borderline resectable patients only: Completion of inducation chemotherpy within 1-3 weeks of study treatment start. Patients that exceed this window should complete an additional cycle of induction chemotherapy prior to initiation of study treatment, per provider discretion.
3. Age ≥ 18 years at time of study entry.
4. Provision to sign and date the consent form.
5. Stated willingness to comply with all study procedures and be available for the duration of the study.
6. Ability to swallow tablets by mouth.
7. ECOG performance status ≤2 or KPS ≥60%
8. Absolute neutrophil count ≥ 1,000/mcL
9. Platelets ≥ 70,000/mcL
10. Hemoglobin ≥ 9 g/dL, patients may be transfused to meet this criterion
11. Serum albumin ≥ 2.8 g/dL
12. Total Bilirubin ≤ 2mg/dL
13. AST(SGOT)/ALT(SGPT)/ALP ≤ 3 x institutional upper limit of normal (IULN)
14. 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:
15. 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
16. 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
17. 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.

1. Pregnant or breastfeeding. Patients must have a negative serum or urine pregnancy test within 5 days of study treatment.
2. Previous treatment of the current malignancy with a STAT inhibitor.
3. 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.
4. 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.
5. Ongoing toxicity (except alopecia) due to a prior therapy, unless returned to baseline or Grade 1 or less.
6. Has had major surgery within 3 weeks prior to starting IP or has not recovered from major side effects due to surgery.
7. 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.
8. 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.
9. History of cerebrovascular accident or stroke within the previous 2 years.
10. History of hepatic encephalopathy.
11. Uncontrolled or symptomatic hypercalcemia (ionized calcium \>1.5 mmol/L, calcium \>12 mg/dL, or corrected serum calcium \>ULN).
12. Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
13. History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition as TTI-101 (hydroxyl-naphthalene sulfonamides).
14. 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).
15. History of malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the IP.
16. 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.
17. 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.
18. 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.
19. Prior treatment for pancreatic cancer in the past 2 years and outside of the induction chemotherapy received for the current diagnosis.
20. Measurable distant metastases on re-staging imaging post chemotherapy. tCurrently 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.
21. A history of allergic reactions attributed to compounds of similar chemical or biologic composition to TTI-101.

Contacts and Locations

Study Contact

Alex Fonder

CONTACT

1-303-724-5046

alex.fonder@cuanschutz.edu

Principal Investigator

David Binder, MD, PhD

PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Study Locations (Sites)

University of Colorado

Aurora, Colorado, 80045

United States

Collaborators and Investigators

Sponsor: University of Colorado, Denver

David Binder, MD, PhD, PRINCIPAL_INVESTIGATOR, University of Colorado, Denver

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-01-16

Study Completion Date2028-09

Study Record Updates

Study Start Date2024-01-16

Study Completion Date2028-09

Terms related to this study

Keywords Provided by Researchers

borderline resectable
locally advanced

Additional Relevant MeSH Terms

Pancreatic Cancer