A PHASE 1 STUDY TO EVALUATE THE EFFECT OF HEPATIC IMPAIRMENT ON THE PHARMACOKINETICS AND SAFETY OF LORLATINIB IN ADVANCED CANCER PATIENTS
Description
Brief Summary
This is a phase 1 study in advanced cancer patients with varied hepatic fucntions to evaluate
the potential effect of hepatic impairment on pharmacokinetics and safety of lorlatinib and
provide dose recommendation for patients with hepatic impairment if possible.
Detailed Description
This will be a Phase 1, open label, multi center, multiple dose, non randomized, Phase 1
clinical trial of lorlatinib in advanced cancer patients with varying degrees of hepatic
impairment and necessary age , weight , and gender matched prospect normal hepatic function
patients. This study is intended to evaluate the potential effect of hepatic impairments on
the PK and safety of lorlatinib after daily administration of lorlatinib and to provide
dosing recommendation for patients with varied degree of hepatic impairment if possible.
Patients in the study will be assigned to different groups (A1, normal liver function,
control for group B; A2, normal liver function, control for group C; B, mild hepatic
impairment; C, moderate hepatic impairment; D, severe hepatic impairment) according to their
liver function. The enrollment of approximately 76 advanced cancer patients is anticipated in
this study in order to have 8 PK-evaluable patients in each of Groups A1, A2, B and C, and 6
PK-evaluable patients in Group D for final statistical analysis. Evaluable patients are those
who complete the planned PK sample collection on Cycle 2 Day 1 and have no lorlatinib dose
modification until completion of Cycle 2 Day 1 PK evaluation. Patients who are not evaluable
for PK will be replaced. Each patient will be treated with repeated oral once daily doses of
lorlatinib in 21-day cycles until disease progression, patient refusal, or unacceptable
toxicity occurs. The dose schedule may be modified as necessary for individual patients
according to tolerability.
Phase
N/AInclusion and Exclusion Criteria
- Histologically or cytologically confirmed solid malignancy or lymphoma that is metastatic or unresectable, and for which standard curative or palliative measures do not exist, or are no longer effective;
- Biliary obstruction with a biliary drain or stent;
- Neurologically stable gliomas and brain metastases;
- ECOG performance status of 0, 1, or 2;
- adequate bone marrow function;
- adequate pancreatic function;
- adequate renal function;
- female patients with negative pregnancy test
- untreated esophageal varices; uncontrolled ascites;
- episodes of hepatic encephalopathy within the last 4 weeks;
- spinal cord compression; major surgery within 4 weeks prior to enrollment;
- radiation therapy within 2 weeks prior to enrollment;
- last anti-cancer treatment within 2 weeks prior to screening;
- previous high-dose chemotherapy requiring stem cell rescue;
- prior to irradiation to >25% of the bone marrow;
- gastrointestinal abnormalities;
- known prior or suspected hypersensitivity to lorlatinib or lorlatinib tablet;
- clinically significant bacterial, fungal or viral infections for non-liver cancer patients;
- clinically significant cardiovascular disease;
- uncontrolled hypertension; acute pancreatitis with predisposing characteristics;
- history of grade 3 or 4 interstitial fibrosis or interstitial lung disease;
- active hemoelysis or evidence of biliary sepsis;
- prior major gastrointestinal surgery;
- concurrent use of known strong CYP3A inhibitors, inducers and P-gp substrates with a narrow therapeutic index;
- concurrent use of CYP3A substrates with narrow therapeutic indices;
- prior treatment with lorlatinib; active bleeding disorder
Sites
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.