A Phase 1 Study to Assess the Effect of Hepatic Impairment on the Pharmacokinetics of Repotrectinib in Advanced Cancer Patients

Metastatic Solid Tumor Clinical Trial

Official title:

A Phase 1 Study to Assess the Effect of Hepatic Impairment on the Pharmacokinetics of Repotrectinib in Advanced Cancer Patients

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05828277
• Other study ID #: CA127-1026
• Secondary ID: CA127-1026TPX-00
• Status: Withdrawn
• Phase: Phase 1
• Start date: July 28, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: September 2023
• Source: Turning Point Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 31, 2025
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Locally Advanced Solid Tumor
• Metastatic Solid Tumor
• Neoplasms

Intervention

Drug:
• repotrectinib (TPX-0005)
Oral repotrectinib (TPX-0005)

Locations

Country	Name	City	State
Spain	Local Institution - 4103	Madrid
United States	Gabrail Cancer Research Center	Canton	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Turning Point Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration-time curve (AUC) of repotrectinib	AUC0-t: Area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration	Within 22 days of first repotrectinib dose
Primary	Maximum Observed Plasma Concentration (Cmax) of repotrectinib	Cmax: Evaluate the maximum plasma concentration	Within 22 days of first Repotrectinib dose
Secondary	Evaluate safety and tolerability	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	28 days after last dose of repotrectinib