An Open-label, Multi-center, Non-randomized Phase Ib Study to Investigate the Safety, Efficacy, and Pharmacokinetics of BAY 73-4506 "Regorafenib", Administered in Combination With Pemetrexed and Cisplatin in Patients With Advanced Nonsquamous Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 1
- Intervention
- Regorafenib (BAY73-4506) - sequential / Cisplatin / Pemetrexed
- Conditions
- Small Cell Lung Carcinoma
- Sponsor
- Bayer
- Enrollment
- 9
- Primary Endpoint
- Pharmacokinetics assessments of Alimta, Cisplatin, and regorafenib in Cycle 1 and 2
- Status
- Terminated
- Last Updated
- 11 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age \>= 18 years.
- •Histological or cytological diagnosis of metastatic Stage IV or locally advanced, unresectable confirmed Stage IIIB nonsquamous Non-Small Cell Lung Cancer (NSCLC) not amenable to local therapy with curative intent.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2
- •Life expectancy of at least 12 weeks.
- •Adequate bone marrow, liver, and renal function
- •Controlled blood pressure \[defined as systolic Blood Pressure (BP) \<=150 mmHg and diastolic Blood Pressure (BP) \<= 90 mmHg\]
- •Men and women of childbearing potential enrolled in this study must use adequate barrier birth control measures during the course of the study
Exclusion Criteria
- •Sensory neuropathy with sensory alterations or paresthesia (including tingling), interfering with function
- •Hearing impairment
- •Persistent proteinuria of Common Toxicity Criteria (CTC) Grade 3 or higher
- •Cardiac disease: congestive heart failure \> New York Heart Association (NYHA) Class II; patients must not have unstable angina (anginal symptoms at rest) or new-onset angina (began within the last 3 months) or myocardial infarction within the past 6 months; cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- •Brain metastasis: patients with neurological symptoms should undergo a Computerized Tomography (CT) scan / Magnetic Resonance Imaging (MRI) of the brain to exclude any new or progressive brain metastasis. Patients with brain metastases are excluded from the trial
- •Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication
- •Pulmonary hemorrhage/bleeding event \> Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 within 4 weeks prior to the start of study treatment. Clinically significant hemoptysis (1 teaspoon or more) in the past 3 months
- •Any other hemorrhage/bleeding event \> CTCAE Grade 3 within 4 weeks prior to the start of study treatment
- •Evidence or history of bleeding diathesis or coagulopathy
- •Centrally located tumors with radiologic evidence (CT or MRI) of local invasion of major blood vessels
Arms & Interventions
Arm 1
Intervention: Regorafenib (BAY73-4506) - sequential / Cisplatin / Pemetrexed
Arm 2
Intervention: Regorafenib (BAY73-4506) - continuous / Cisplatin / Pemetrexed
Outcomes
Primary Outcomes
Pharmacokinetics assessments of Alimta, Cisplatin, and regorafenib in Cycle 1 and 2
Time Frame: end of cycle 2
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)
Secondary Outcomes
- Tumor Assessments according to Response Evaluation Criteria in Solid Tumors (RECIST) every second cycle(3 years (depending on the treatment duration of individual patients))
- Biomarkers (includes but not limited to plasma protein analysis of angiogenesis-related proteins, DNA mutational anaylsis of tumor tissue and plasma)(3 years (depending on the treatment duration of individual patients))