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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01187615
First received: July 16, 2010
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Small Cell Lung Carcinoma
Drug: Regorafenib (BAY73-4506) - sequential / Cisplatin / Pemetrexed
Drug: Regorafenib (BAY73-4506) - continuous / Cisplatin / Pemetrexed
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics assessments of Alimta, Cisplatin, and regorafenib in Cycle 1 and 2 [ Time Frame: end of cycle 2 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: August 2010
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: 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.
Experimental: Arm 2 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01187615

Locations
United States, Connecticut
New Haven, Connecticut, United States, 06519
United States, Nevada
Las Vegas, Nevada, United States, 89135-3011
United States, New York
New York, New York, United States, 10065
United States, North Carolina
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01187615     History of Changes
Other Study ID Numbers: 14458
Study First Received: July 16, 2010
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
Nonsquamous Non-small cell lung cancer
Phase I

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Small Cell Lung Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 28, 2014