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

Primary Purpose

Small Cell Lung Carcinoma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

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

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

About this trial

This is an interventional treatment trial for Small Cell Lung Carcinoma focused on measuring Nonsquamous Non-small cell lung cancer, Phase I

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm 1

Arm 2

Arm Description

Outcomes

Primary Outcome Measures

Number of participants with treatment related toxicities and adverse events and change from baseline in vitals signs and laboratory parameters

Pharmacokinetics assessments of Alimta, Cisplatin, and regorafenib in Cycle 1 and 2

Secondary Outcome Measures

Biomarkers (includes but not limited to plasma protein analysis of angiogenesis-related proteins, DNA mutational anaylsis of tumor tissue and plasma)

Tumor Assessments according to Response Evaluation Criteria in Solid Tumors (RECIST) every second cycle

Full Information

NCT ID

NCT01187615

First Posted

July 16, 2010

Last Updated

July 7, 2014

Sponsor

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT01187615

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2014

Overall Recruitment Status

Terminated

Study Start Date

August 2010 (undefined)

Primary Completion Date

June 2012 (Actual)

Study Completion Date

June 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Small Cell Lung Carcinoma

Keywords

Nonsquamous Non-small cell lung cancer, Phase I

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1

Arm Type

Experimental

Arm Title

Arm 2

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

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

Intervention Description

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

Intervention Name(s)

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

Intervention Description

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.

Primary Outcome Measure Information:

Title

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)

Title

Pharmacokinetics assessments of Alimta, Cisplatin, and regorafenib in Cycle 1 and 2

Time Frame

end of cycle 2

Secondary Outcome Measure Information:

Title

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)

Title

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bayer Study Director

Organizational Affiliation

Bayer

Official's Role

Study Director

Facility Information:

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06519

Country

United States

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89135-3011

Country

United States

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

26003007

Citation

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.

Results Reference

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

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