Oral STAT3 Inhibitor, TTI-101, in Patients With Advanced Cancers
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|ClinicalTrials.gov Identifier: NCT03195699|
Recruitment Status : Recruiting
First Posted : June 22, 2017
Last Update Posted : June 16, 2022
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Head and Neck Squamous Cell Carcinoma Non Small Cell Lung Cancer Hepatocellular Cancer Colorectal Cancer Gastric Adenocarcinoma Melanoma Advanced Cancer||Drug: TTI-101||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of TTI-101, an Oral Inhibitor of Signal Transducer and Activator of Transcription (STAT) 3, in Patients With Advanced Cancers|
|Actual Study Start Date :||November 15, 2017|
|Estimated Primary Completion Date :||October 1, 2023|
|Estimated Study Completion Date :||October 1, 2023|
Experimental: Dose escalation study
Participants will receive up to 4 dose levels of TTI-101 to determine RP2D
Experimental: Dose expansion study
Enrollment in the dose expansion may commence with approval from the safety review committee. Participants will be enrolled and treated at the RP2D of TTI-101
Experimental: Food effect study
Participants will be treated with TTI-101 at the RP2D under fed and fasted conditions to assess the bioavailability of TTI-101 and to determine the best conditions for taking the study drug
Experimental: Dose expansion, cross-over study
Participants will be administered different formulations of TTI-101 to compare bioavailability.
- Maximum Tolerated Dose of TTI-101 [ Time Frame: 28 days ]To determine the maximum tolerated dose (MTD), dose-limiting toxicities, and tolerability of TTI-101 administered orally to patients with advanced breast cancer and other solid tumors. Dose-limiting toxicity is defined as a Grade 3 or above adverse event (using CTCAE v5.0) within the first treatment cycle (28-days).
- Pharmacokinetics - Cmax [ Time Frame: 18 months ]Cmax(obs) will be determined by direct inspection of the plasma drug concentration versus time data point values.
- Pharmacokinetics - Tmax [ Time Frame: 18 months ]Tmax(obs) will also be determined by direct inspection of the plasma drug concentration versus time data point values.
- Pharmacokinetics - AUC(0-t) [ Time Frame: 18 months ]AUC(0-t) (where t = the time point for the last sample on the pharmacokinetic profile in which quantifiable drug was detected) will be estimated using linear or linear/log trapezoidal calculation.
- Pharmacodynamics of TTI-101 in patients [ Time Frame: 18 months ]Levels of pY-STAT3 measured before and before and after receiving TTI-101 will be measured.
- Complete Response (CR) - Target Lesions [ Time Frame: 18 months ]Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
- Partial Response (PR) - Target Lesions [ Time Frame: 18 months ]Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- Progressive Disease (PD) - Target Lesions [ Time Frame: 18 months ]Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
- Stable Disease (SD) - Target Lesions [ Time Frame: 18 months ]Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
- Complete Response (CR) - Non-target Lesions [ Time Frame: 18 months ]Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
- Non-CR/Non-PD - Non-target Lesions [ Time Frame: 6 months ]Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.
- Progressive Disease (PD) - Non-target Lesions [ Time Frame: 18 months ]Progressive Disease (PD): Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression).
- Best Overall Response [ Time Frame: 18 months ]The best overall response is the best response recorded from the start of the study treatment until the end of treatment, taking into account any requirement for confirmation. The patient's best overall response assignment will depend on the findings of both target and non-target disease and will also take into consideration the appearance of new lesions.
- Explore association between biomarkers and antitumor efficacy and survival outcome based on RECIST 1.1 for uHCC patients. [ Time Frame: 18 months ]Assess the association between STAT3 inhibition, fibrosis (if applicable), antitumor activity and survival outcomes after receiving TTI-101. Tissue and blood immune monitoring will be based on 2 biopsies. Association between biomarkers including pY-STAT3, PD1, and PD-L1 proteins expression by IHC, gene expression profiling, and antitumor efficacy and survival outcome of TTI-101 based on RECIST 1.1.
- Assess the effect of food on bioavailability [ Time Frame: 18 months ]Assess the effect of food on bioavailability of TTI-101 in the dose expansion phase
- Assess the bioavailability between different formulations of TTI-101 [ Time Frame: 18 months ]Assess the bioavailability between different formulations of TTI-101 in the dose expansion phase
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03195699
|Contact: Lori McDermott, RN/BSN, MSc, PMP||813-334-5173||LMcDermott@cancerinsight.com|
|Contact: Michele Correllfirstname.lastname@example.org|
|United States, Georgia|
|Winship Cancer Institute of Emory University||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Erin T David 404-778-1805 email@example.com|
|United States, Texas|
|The University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Apostolia M. Tsimberidou, MD, PhD 713-792-4259 firstname.lastname@example.org|
|Mays Cancer Center at University of Texas Health Science Center SA||Recruiting|
|San Antonio, Texas, United States, 78229|
|Contact: Epp Goodwin 210-450-5798 CTRCReferral@uthscsa.edu|
|Principal Investigator:||Apostolia Tsimberidou, MD, PhD||The University of Texas MD Anderson Cancer Center|