Determination of Safety, Efficacy, and Pharmacokinetics of "Regorafenib" Combined With Pemetrexed and Cisplatin in Patients With Nonsquamous Non-Small Cell Lung Cancer

NCT ID: NCT01187615

Last Updated: 2014-07-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2012-06-30

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.

Conditions

Small Cell Lung Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Group Type: EXPERIMENTAL

Regorafenib (BAY73-4506) - sequential / Cisplatin / Pemetrexed

Intervention Type: DRUG

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.

Arm 2

Group Type: EXPERIMENTAL

Regorafenib (BAY73-4506) - continuous / Cisplatin / Pemetrexed

Intervention Type: DRUG

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.

Interventions

Regorafenib (BAY73-4506) - sequential / Cisplatin / Pemetrexed

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.

Intervention Type: DRUG

Regorafenib (BAY73-4506) - continuous / Cisplatin / Pemetrexed

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.

Intervention Type: DRUG

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
• The effect of third space fluid, such as pleural effusion and ascites, on pemetrexed is unknown. In patients with clinically significant third space fluid, consideration should be given to draining the effusion prior to study start
• Patients with phaeochromocytoma Excluded Therapies and Medications, Previous and Concomitant
• Prior treatment with a systemic chemotherapy for metastatic NSCLC. Patients who underwent prior systemic treatment or radiotherapy for NSCLC in a neoadjuvant or adjuvant setting are eligible, but no chemotherapy treatment within the last 6 month prior to study entry is allowed

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

New Haven, Connecticut, United States

Las Vegas, Nevada, United States

New York, New York, United States

Chapel Hill, North Carolina, United States

Countries

United States

References

Hellmann MD, Sturm I, Trnkova ZJ, Lettieri J, Diefenbach K, Rizvi NA, Gettinger SN. Preliminary Safety, Pharmacokinetics, and Efficacy of Regorafenib, Cisplatin, and Pemetrexed in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancers. Clin Lung Cancer. 2015 Nov;16(6):514-22. doi: 10.1016/j.cllc.2015.04.003. Epub 2015 Apr 20.

Reference Type: DERIVED

PMID: 26003007 (View on PubMed)

Other Identifiers

14458

Identifier Type: -

Identifier Source: org_study_id