This is a multi-center, open-label, non-randomized Phase I study to define the safety profile, maximum tolerated dose (MTD) and potential pharmacokinetic interaction of regorafenib in combination with pemetrexed and cisplatin in patients with Stage IIIB or Stage IV nonsquamous Non-Small Cell Lung Cancer (NSCLC) and to determine the impact of the combined administration on the pharmacokinetics of regorafenib, pemetrexed, and cisplatin. In Part A of this trial, regorafenib will be administered in a sequential dosing with a seven day wash out period before the next infusion of pemetrexed and cisplatin. Regorafenib will be administered at a dose of 160 mg qd from Day 2 to Day 14 followed by a 7 days break. In Part B of this trial, regorafenib will be administered continuously from Day 1 to Day 21. Only in Cycle 1, regorafenib dosing will start on Day 2 in order to assess the pharmacokinetics of pemetrexed and cisplatin without concomitant regorafenib dosing.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
9
In Part A of this trial, regorafenib will be administered in a sequential dosing with a seven day wash out period before the next infusion of pemetrexed and cisplatin. Regorafenib will be administered at a dose of 160 mg qd from Day 2 to Day 14 followed by a 7 days break. Pharmacokinetics of regorafenib will be assessed on Day 14 of Cycle 1 and Day 1 of Cycle 2.
In Part B of this trial, regorafenib will be administered continuously from Day 1 to Day 21. Only in Cycle 1, regorafenib dosing will start on Day 2 in order to assess the pharmacokinetics of pemetrexed and cisplatin without concomitant regorafenib dosing. Pharmacokinetics of regorafenib will be assessed on Day 21 of Cycle 1 and on Day 1 of Cycle 2.
Unnamed facility
New Haven, Connecticut, United States
Unnamed facility
Las Vegas, Nevada, United States
Unnamed facility
New York, New York, United States
Unnamed facility
Chapel Hill, North Carolina, United States
Number of participants with treatment related toxicities and adverse events and change from baseline in vitals signs and laboratory parameters
Time frame: 3 years (depending on the treatment duration of individual patients)
Pharmacokinetics assessments of Alimta, Cisplatin, and regorafenib in Cycle 1 and 2
Time frame: end of cycle 2
Biomarkers (includes but not limited to plasma protein analysis of angiogenesis-related proteins, DNA mutational anaylsis of tumor tissue and plasma)
Time frame: 3 years (depending on the treatment duration of individual patients)
Tumor Assessments according to Response Evaluation Criteria in Solid Tumors (RECIST) every second cycle
Time frame: 3 years (depending on the treatment duration of individual patients)
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