A Randomized (PhaseII), Double-blind, Multicenter Phase I/II Trial of Pemetrexed, Carboplatin Plus or Minus Sorafenib in the First-line Treatment of Patients With Stage IIIb or IV Non-Small Cell Lung Cancer

University Hospital Muenster1 site in 1 country12 target enrollmentMay 2007

ConditionsCarcinoma, Non-Small-Cell Lung

Interventionspemetrexed, carboplatin, sorafenib pemetrexed, carboplatin, placebo

Drugspemetrexed, carboplatin, sorafenib pemetrexed, carboplatin, placebo

Overview

Phase: Phase 1
Intervention: pemetrexed, carboplatin, sorafenib
Conditions: Carcinoma, Non-Small-Cell Lung
Sponsor: University Hospital Muenster
Enrollment: 12
Locations: 1
Primary Endpoint: Ph.1: Identify the recommended phase II dose of sorafenib for combination therapy with carboplatin and pemetrexed
Status: Terminated
Last Updated: 16 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The majority of patients with advanced NSCLC treated with standard platinum based chemotherapy regimens ultimately develop disease progression. Active therapies with improved toxicity profiles are clearly needed in this setting. The primary objective of this trial is to assess the toxicity profile and to determine the effect on progression free survival and time to progression in patients with advanced NSCLC treated with sorafenib in addition to carboplatin and pemetrexed.

Registry

clinicaltrials.gov

Start Date

May 2007

End Date

January 2010

Last Updated

16 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

University Hospital Muenster

Eligibility Criteria

Inclusion Criteria

•Histologically or cytologically confirmed NSCLC
•Locally advanced (stage IIIB with malignant pleural or pericardial effusion) or metastatic (stage IV) NSCLC
•No prior systemic chemotherapy
•Prior local radiotherapy is allowed if it is completed at least 3 weeks prior to the first dose of study medication; also concomitant palliative radiotherapy to an existing bone lesion for pain control is allowed
•Prior surgery is allowed if it is performed at least 4 weeks prior to the first dose of study medication and patient should be fully recovered.
•Must have measurable disease with at least one lesion with a longest diameter measured as ≥ 2 cm with conventional techniques or as ≥ 1 cm with spiral CT
•Age ≥18 years old
•ECOG performance score (PS) 0-1
•Life expectancy of at least 12 weeks
•Adequate bone marrow, renal and hepatic function

Exclusion Criteria

•Any prior systemic anticancer therapy including cytotoxic therapy, targeted agents, experimental therapy (treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study enrollment), adjuvant, or neo-adjuvant therapy for NSCLC
•Any participation in a clinical trial 30 days prior to study entry and concomitantly to the study
•Cardiac disease: Congestive heart failure \> class II NYHA. Patients must not have unstable angina (angina 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
•Uncontrolled hypertension defined as systolic blood pressure \> 150 mm Hg or diastolic pressure \> 90 mm Hg, despite optimal medical management
•Documented brain metastases (unless the patient is \> 6 months from definitive therapy for brain metastases, has a negative imaging study within 4 weeks of study entry and has been off corticosteroids for at least 4 weeks before study enrolment). Brain imaging (CT scan/MRI) is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients.
•Patients with seizure disorder requiring medication (such as steroids or antiepileptics)
•Known HIV infection or chronic hepatitis B or C
•Active clinically serious infections \> CTCAE Grade 2
•Presence of clinically significant third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study enrolment

Arms & Interventions

1

Pemetrexed, Carboplatin plus Sorafenib in the first-line treatment of patients with stage IIIb or IV NSCLC

Intervention: pemetrexed, carboplatin, sorafenib

2

Pemetrexed, Carboplatin plus placebo in the first-line treatment of patients with stage IIIb or IV NSCLC

Intervention: pemetrexed, carboplatin, placebo

Outcomes

Primary Outcomes

Ph.1: Identify the recommended phase II dose of sorafenib for combination therapy with carboplatin and pemetrexed

Time Frame: July 2008

Ph.2: Compare the PFS of carboplatin/pemetrexed + sorafenib or carboplatin/pemetrexed + placebo in patients with stage IIIb or IV non-small cell lung cancer

Time Frame: May 2009

Secondary Outcomes

Ph.1: Determine dose limiting toxicity(July 2008)
Ph 1: Determine the safety profile of the combination treatment(July 2008)
Ph 1: descriptive analysis of efficacy(July 2008)
Ph.2: Compare PFS of carboplatin/pemetrexed + sorafenib or carboplatin/pemetrexed + placebo in patients with stage IIIb or IV NSCLC(May 2009)
Ph 2: Assess time to progression in patients treated with either regimen(May 2009)
Ph 2: Determine the overall survival in patients treated with either regimen(May 2009)
Ph 2: Determine the objective response rate (CR, PR), disease control rate (CR,PR,SD), time to response and duration of response(May 2009)
Ph 2: Identify surrogate markers from the tumor biopsy or resection specimen from the time of diagnosis that predict response(May 2009)
Ph 2: Assess Quality of Life of patients treated with either regimen(May 2009)
Ph 2: Assess feasibility and toxicity profile of this regimen(May 2009)