Study to Evaluate the Efficacy and Safety of TT-00420 (Tinengotinib) in Cholangiocarcinoma

NCT ID: NCT04919642

Last Updated: 2024-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-07
• Study Completion Date: 2024-02-28

Brief Summary

This study is an open-label, multicenter study to evaluate the efficacy and safety of TT-00420 tablet in adult patients with advanced cholangiocarcinoma.

Detailed Description

This is a Phase II, open-label study to evaluate the efficacy and safety of TT00420 in patients with advanced/metastatic and surgically unresectable cholangiocarcinoma (CCA) with 1) FGFR 2 fusions who failed prior FGFR inhibitor treatment, 2) FGFR2 fusions who responded on prior FGFR inhibitor treatment, 3) with other FGFR alterations, or 4) whose tumors do not contain a detectable FGFR alteration.

Conditions

Cholangiocarcinoma; FGFR2 Fusion; FGFR2 Gene Mutation; FGFR1 Alteration; FGFR3 Alteration

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A1

FGFR2 fusions who have failed at least one previous treatment with an FGFR inhibitor

Group Type: EXPERIMENTAL

TT-00420

Intervention Type: DRUG

TT-00420 tablet, administered orally once daily

Cohort A2

FGFR2 fusions who have previously responded on at least one previous treatment with an FGFR inhibitor and discontinued due to disease progression

Group Type: EXPERIMENTAL

TT-00420

Intervention Type: DRUG

TT-00420 tablet, administered orally once daily

Cohort B

Other FGFR alterations, including FGFR2 mutations and FGFR1/3 alterations, including fusions

Group Type: EXPERIMENTAL

TT-00420

Intervention Type: DRUG

TT-00420 tablet, administered orally once daily

Cohort C

Negative for FGFR alterations (FGFR wild-type)

Group Type: EXPERIMENTAL

TT-00420

Intervention Type: DRUG

TT-00420 tablet, administered orally once daily

Interventions

TT-00420

TT-00420 tablet, administered orally once daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. ≥ 18 years of age, at the time of signing informed consent

2. Histologically or cytologically documented advanced/metastatic or surgically unresectable cholangiocarcinoma who have received at least one line of prior systemic chemotherapy. Patients will be assigned to 1 of 4 cohorts:

• Cohort A1: FGFR2 fusions who have failed at least one previous treatment with an FGFR inhibitor
• Cohort A2: FGFR2 fusions who have previously responded on at least one previous treatment with an FGFR inhibitor
• Cohort B: other FGFR alterations, including FGFR2 mutations and FGFR1/3 alterations, including fusions
• Cohort C: negative for FGFR alterations (FGFR wild-type)

3. At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors5

4. Documentation of FGFR gene alteration status

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

6. Adequate organ function confirmed at screening and within 10 days of initiating treatment, as evidenced by:

• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• Hemoglobin (Hgb) ≥ 8 g/dl
• Platelets (plt) ≥ 75 x 10^9/L
• aspartate aminotransferase/serum glutamate oxaloacetate transaminase (AST/SGOT) and alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT) ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastases are present
• Total bilirubin ≤ 1.5 x ULN
• Calculated creatine clearance ≥ 50 mL/min (Cockcroft Gault formula

7. Negative pregnancy test within 72 hours before starting study treatment in all premenopausal women and women < 12 months after the onset of menopause

8. Must agree to take sufficient contraceptive methods to avoid pregnancy (including male and female participants) during the study and until at least 6 months after ceasing study treatment

9. Able to sign informed consent and comply with the protocol

Exclusion Criteria

1. Women who are pregnant or lactating

2. Women of child-bearing potential (WOCBP) who do not use adequate birth control

3. Patients with untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed (e.g. evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain/CNS metastases) Note: Patients with treated brain metastases that are off corticosteroids and have been clinically stable for 28 days are eligible for enrollment.

4. Patients with a known concurrent malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, carcinoma in situ of the cervix or other noninvasive or indolent malignancy that has previously undergone potentially curative therapy.

5. Patients with the following mood disorders as judged by the Investigator or a psychiatrist:

• Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia; a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
• ≥ CTCAE grade 3 anxiety

6. Impaired cardiac function or significant diseases, including but not limited to any of the following:

• left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO)
• Congenital long QT syndrome
• QTcF ≥ 480 msec on screening ECG
• Unstable angina pectoris ≤ 3 months prior to starting study drug
• Acute myocardial infarction ≤ 3 months prior to starting study drug

7. Patients with uncontrolled hypertension (defined as blood pressure of ≥ 150 mmHg systolic and/or ≥ 90 mmHg diastolic at Screening)

8. Patients with:

• unresolved diarrhea ≥ CTCAE grade 2, or
• impairment of gastrointestinal (GI) function, or
• GI disease that may significantly alter the absorption of TT-00420.

9. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. uncontrolled hypertriglyceridemia [triglycerides > 500 mg/dL], or active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol

10. Patients who have received chemotherapy, targeted therapy, or immunotherapy ≤ 5 half-lives or 3 weeks, whichever is shorter, (6 weeks for nitrosourea or mitomycin-C) prior to starting study drug

11. Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from adverse events of prior therapy

12. Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from adverse events of prior therapy

13. Patients who are currently receiving treatment with therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants

14. Patients who are currently receiving treatment with strong CYP3A inhibitors or inducers, or sensitive substrates of CYP3A4 ≤ 2 weeks prior to starting study drug.

15. Patients who are using a proton pump inhibitor within 4 days prior to the start of study therapy or a histamine-2 blocker within 2 days prior to the start of study therapy.

16. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory; patients with well controlled HIV might be enrolled per investigator's discretion and Sponsor approval)

17. Evidence of active infection with Hepatitis B or Hepatitis C that is not adequately controlled. For patients with known prior history of Hepatitis B or Hepatitis C, enrollment may be allowed per investigator's discretion and Sponsor approval.

18. Inability to swallow or tolerate oral medication

19. Has a history or current evidence of any condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the patient's safe participation and compliance in the trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

TransThera Sciences (Nanjing), Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Milind Javle, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

Providence Cancer Center

Anchorage, Alaska, United States

City of Hope

Duarte, California, United States

University of California, Los Angeles, School of Medicine

Santa Monica, California, United States

USO Oncology Network- Rocky Mountain Cancer Centers

Denver, Colorado, United States

Mount Sinai Medical Center

Miami Beach, Florida, United States

University of Chicago Medical Center - Duchossis Center for Advanced Medicine

Chicago, Illinois, United States

University of Maryland - Marlene and Stewart Greenebaum Cancer Center

Baltimore, Maryland, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Henry Ford Health Center

Detroit, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Comprehensive Cancer Center of Nevada

Las Vegas, Nevada, United States

Summit Medical Group - Florham Park Campus

Florham Park, New Jersey, United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Ruttenberg Treatment Center - Mount Sinai

New York, New York, United States

USOR Oncology Network- New York Oncology

New York, New York, United States

Stony Brook University - Long Island Cancer Center

Stony Brook, New York, United States

University of Cincinnati Cancer Institute

Cincinnati, Ohio, United States

University Hospitals Seidman Cancer Center

Cleveland, Ohio, United States

USO Oncology Network-Northwest Cancer Specialists, P.C.

Portland, Oregon, United States

Medical College of South Carolina

Charleston, South Carolina, United States

The University of Tennessee Medical Center

Knoxville, Tennessee, United States

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, United States

Methodist Dallas Medical Center

Dallas, Texas, United States

Parkland Health & Hospital System

Dallas, Texas, United States

University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center

Dallas, Texas, United States

Houston Methodist Hospital - Outpatient Center

Houston, Texas, United States

UT MD Anderson Cancer Center

Houston, Texas, United States

USO Oncology Network-Texas Oncology

Tyler, Texas, United States

USO Oncology Network-Virginia Oncology Associates - Brock Cancer Center - Norfolk

Norfolk, Virginia, United States

USO Oncology Network-Oncology and Hematology Associates of Southwest Virginia, Inc.

Roanoke, Virginia, United States

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

TT420C1206

Identifier Type: -

Identifier Source: org_study_id