Clinical trial for Hepatocellular Carcinoma
Official title A Study of TTI-101 as Monotherapy and in Combination in Participants With Locally Advanced or Metastatic, and Unresectable Hepatocellular Carcinoma
ClinicalTrials.gov ID: NCT05440708
What this study is testing
What is TTI-101?
TTI-101 is an investigational oral tablet being studied as a potential treatment for hepatocellular carcinoma.
Plain-language explanation of the investigational treatment. It is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- The study wants to see how safe TTI‑101 is when taken by mouth, alone or with other cancer medicines, and to find the best dose. It also looks at whether the drug shows early signs of working against liver cancer.
- Who it's for
- Adults with liver cancer that has spread or cannot be removed by surgery.
- What's involved
- Participants will take TTI‑101 pills, sometimes together with other cancer drugs, and will have regular clinic visits, blood tests, and scans to monitor safety and any changes in the cancer.
- Time commitment
- The study lasts several months, with visits every few weeks for medication, tests, and doctor check‑ups.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Able to understand and willing to provide informed consent and able to comply with the study procedures and restrictions.
- Age ≥18 years at the time of informed consent.
- Have histologically or radiographically (Liver Imaging Reporting and Data Systems category 5) confirmed diagnosis of locally advanced or metastatic...
- Cohorts A and B only: Willing to provide a representative fresh tumor tissue specimen prior to enrollment.
- Measurable disease as per RECIST Version 1.1. Participants who received prior local therapy are eligible provided the target lesion(s) have not been...
You likely can't join if
- Pregnant or breastfeeding.
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- History of leptomeningeal disease.
- Previous treatment of the current malignancy with a signal transducer and activator of transcription (STAT) inhibitor.
- Standard therapy including chemotherapy, immunotherapy, biologic therapy, or any other anticancer therapy within 28 days (or 5 elimination half-lives...
- Any investigational agent within 28 days (or 5 elimination half-lives for a non-cytotoxic investigational therapy, whichever is shorter) of Cycle 1...
See the full eligibility criteria
Who can join
- Able to understand and willing to provide informed consent and able to comply with the study procedures and restrictions.
- Age ≥18 years at the time of informed consent.
- Have histologically or radiographically (Liver Imaging Reporting and Data Systems category 5) confirmed diagnosis of locally advanced or metastatic, and unresectable HCC.
- Cohorts A and B only: Willing to provide a representative fresh tumor tissue specimen prior to enrollment. The fresh tumor specimen must be obtained after progression on the prior therapy.
- Measurable disease as per RECIST Version 1.1. Participants who received prior local therapy are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within...
- Able to swallow tablets.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Absolute neutrophil count (ANC) ≥1.5 × 10\^9/L (1500/μL) without granulocyte colony-stimulating factor support.
- Lymphocyte count ≥0.5 × 10\^9/L (500/μL).
- Platelet count ≥75 × 10\^9/L (75,000/μL) without transfusion.
- Hemoglobin ≥90 g/L (9 g/dL). Participants may be transfused to meet this criterion.
- Serum albumin ≥28 g/L (2.8 g/dL).
- AST, ALT, and alkaline phosphatase (ALP) ≤5 × upper limit of normal (ULN).
- Serum bilirubin ≤2 mg/dL.
- creatinine clearance ≥40 mL/min calculated using the Cockcroft-Gault formula, or
- 24-hour urine collection.
- Prothrombin time/international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT) ≤2 × ULN, except for participants receiving anticoagulation therapy.
- Child-Pugh class A or B7 within 7 days prior to enrollment.
- Have a negative serum pregnancy test at screening.
- Not be breastfeeding or lactating.
- Agree to use a highly effective method of birth control for the duration of the study and for at least 30 days after the last dose in the study.
- Agree to use a condom for at least 30 days after the last dose in the study even if vasectomized in order to prevent delivery of the drug via seminal fluid.
- Agree to abstain from sperm donation through 30 days after administration of the last dose of the study treatment.
- In addition to the general , participants enrolled in Cohort B must have demonstrated objective progression following at least 2 cycles of first-line anti-PD-1 or anti-PD-L1 monotherapy or combination therapy.
- In addition to the general , participants enrolled in Cohort C must be naïve to systemic treatment for locally advanced or metastatic, and unresectable HCC.
- Must have had an evaluation (gastroduodenoscopy) for the presence of varices within 6 months prior to initiation of bevacizumab therapy.
- Agree to use contraception as specified in the general for at least 5 months after the last dose of atezolizumab and at least 6 months after the last dose of bevacizumab in accordance with the approved prescribing...
What rules you out
- Pregnant or breastfeeding.
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- History of leptomeningeal disease.
- Previous treatment of the current malignancy with a signal transducer and activator of transcription (STAT) inhibitor.
- Standard therapy including chemotherapy, immunotherapy, biologic therapy, or any other anticancer therapy within 28 days (or 5 elimination half-lives for non-cytotoxics, whichever is shorter) of Cycle 1 Day 1 (6 weeks...
- Any investigational agent within 28 days (or 5 elimination half-lives for a non-cytotoxic investigational therapy, whichever is shorter) of Cycle 1 Day 1 or 5 half-lives for a small molecule/targeted therapy.
- Extensive prior radiotherapy to more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years from enrollment.
- Herbal preparations are not allowed throughout the study. These herbal medications include but are not limited to St.
- Is not fully recovered from all coronavirus disease 2019 (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 investigational product (IP) or has not recovered from major side effects due to surgery.
- Significantly impaired cardiac function such as unstable angina pectoris, congestive heart failure with New York Heart Association Class III or IV, myocardial infarction within the last 12 months prior to study entry
- 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 difficulty swallowing oral medications, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the IP.
- Has a known history of human immunodeficiency virus (HIV) infection.
- Participants with chronic hepatitis B virus (HBV) infection, unless screening viral load \<500 IU/mL on stable doses of antiviral therapy.
- History of malignancy other than HCC 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...
- 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.
- Inadequately controlled arterial hypertension (defined as systolic blood pressure [BP] ≥150 mmHg and/or diastolic BP ≥100 mmHg), based on an average of ≥3 BP readings on ≥2 sessions.
- Participant has received prior systemic chemotherapy for locally advanced or metastatic and/or unresectable HCC.
- Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding and a prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of...
- Urine dipstick for proteinuria ≥2+ at screening. If a 24-hour urine collection shows \<1 g of protein in 24 hours, the participant is eligible.
- Current or recent (within 10 days of first dose of study treatment) use of aspirin (\>325 mg/day) or treatment with dipyridamole, ticlopidine, clopidogrel, and cilostazol.
- Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants.
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days prior to the first dose of bevacizumab.
- History of gastrointestinal perforation or evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
- Metastatic disease that involves major airways or blood vessels. Participants with portal or hepatic vein involvement are not excluded.
- Participant has experienced any of the following within 6 months prior to enrollment: arterial thromboembolic event (including myocardial infarction, coronary arterial disease, transient ischemic attack, stroke, etc)...
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during pembrolizumab treatment or within 5 months after the last dose of...
- Participants with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
- Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
- Rash must cover \<10% of body surface area.
- Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
- No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral...
- History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed...
- Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor α [TNF-α] agents) within 2...
- Active tuberculosis.
- Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment.
- Prior allogeneic stem cell or solid organ transplantation.
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
The study team makes the final eligibility decision.
Where it is enrolling
- Los Angeles, California, United States
- Orange, California, United States
- Aurora, Colorado, United States
- Tampa, Florida, United States
- Baltimore, Maryland, United States
- Ann Arbor, Michigan, United States
- St Louis, Missouri, United States
- New York, New York, United States
- Oklahoma City, Oklahoma, United States
- Dallas, Texas, United States
- Houston, Texas, United States
- McAllen, Texas, United States
- San Antonio, Texas, United States
- Seattle, Washington, United States
- Spokane, Washington, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part, but confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
This study is enrolling now at Los Angeles, California, United States; Orange, California, United States; Aurora, Colorado, United States; Tampa, Florida, United States; Baltimore, Maryland, United States; Ann Arbor, Michigan, United States and 9 more locations. Enter your location above to see the nearest enrolling site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool that is independent of the study sponsor. Details come from ClinicalTrials.gov. The study team decides eligibility, and your own doctor gives medical advice.