Locally Advanced Solid Tumor, Metastatic Solid Tumor
Conditions
Brief summary
This is a Phase 1 study to evaluate the effect of moderate or severe hepatic impairment on the PK of repotrectinib in patients with advanced cancer.
Detailed description
This is a Phase 1, multicenter, multiple-dose, open-label, nonrandomized study to evaluate the effect of moderate or severe hepatic impairment on the PK of repotrectinib following single and multiple dose administration of repotrectinib in patients with advanced cancer. This study will enroll 8 patients each with moderate hepatic impairment, severe hepatic impairment and normal hepatic function.
Interventions
Oral repotrectinib (TPX-0005)
Sponsors
Turning Point Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumor for which standard curative or palliative measures do not exist or are no longer effective. In case of hepatocellular carcinoma, the diagnosis should be based on at least 1 of the following: 1. The presence of at least 1 lesion, measuring ≥2 cm, with characteristic arterial enhancement and venous washout in the setting of liver cirrhosis and/or hepatitis B or C infection. 2. The presence of liver lesion(s) (as defined in inclusion criteria 3a) with alphafetoprotein ≥ 400 ng/mL. 3. Tissue confirmation. 2. For patients with genetic ROS1 or NTRK 1-3 gene fusion, tissue-based local testing should be documented. 3. Biliary obstruction for whom a biliary drain or stent has been placed are eligible. 4. Eastern Cooperative Oncology Group Performance Status scores 0 to 2. 5. The patient must have no clinically significant change in hepatic disease status within the last 30 days before screening. 6. Patient with ascites must not have a paracentesis within 3 months of screening. 7. Protocol specified baseline hematology and kidney function laboratory values Key
Exclusion criteria
1. Concurrent participation in another therapeutic clinical study. 2. Symptomatic brain metastases or leptomeningeal involvement. 3. Major surgery within 4 weeks. 4. Clinically significant cardiovascular disease. 5. History of non-pharmacologically induced prolonged QT interval corrected for heart rate interval. 6. Known active infections requiring ongoing treatment (bacterial, fungal, or viral, including human immunodeficiency virus positivity). 7. Gastrointestinal disease or other malabsorption syndromes. 8. Current use or anticipated need for drugs that are known to be strong cytochrome P450 (CYP) 3A inhibitors or inducers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration-time curve (AUC) of repotrectinib | Within 22 days of first repotrectinib dose | AUC0-t: Area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration |
| Maximum Observed Plasma Concentration (Cmax) of repotrectinib | Within 22 days of first Repotrectinib dose | Cmax: Evaluate the maximum plasma concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate safety and tolerability | 28 days after last dose of repotrectinib | To evaluate the safety and tolerability of repotrectinib in patients with moderate and severe hepatic impairment and patients with normal hepatic function following single and multiple dose administration of repotrectinib assessed by CTCAE v5.0 |
Countries
Spain, United States
Outcome results
None listed