Phase II Study of Biweekly Carboplatin and Gemcitabine With Bevacizumab as 1st Line Treatment in Patients With Advanced, Inoperable Stage IIIb/IV NSCLC

Masonic Cancer Center, University of Minnesota2 sites in 1 country38 target enrollmentMarch 2007

ConditionsCarcinoma, Non-Small-Cell Lung

InterventionsGemcitabine, Carboplatin, Bevacizumab

DrugsGemcitabine, Carboplatin, Bevacizumab

Overview

Phase: Phase 2
Intervention: Gemcitabine, Carboplatin, Bevacizumab
Conditions: Carcinoma, Non-Small-Cell Lung
Sponsor: Masonic Cancer Center, University of Minnesota
Enrollment: 38
Locations: 2
Primary Endpoint: Time to Progression
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to determine whether treatment with carboplatin and gemcitabine combined with bevacizumab every two weeks will provide increased survival.

Detailed Description

Treatment with Carboplatin and gemcitabine is one of the most active combination therapies used for first-line therapy of NSCLC. The optimum schedule for administration of carboplatin and gemcitabine is currently unknown. The addition of bevacizumab to another comparable platinum combination showed an overall survival advantage and a significantly greater response rate and progression-free survival.

Registry

clinicaltrials.gov

Start Date

March 2007

End Date

May 2010

Last Updated

8 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Masonic Cancer Center, University of Minnesota

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) EXCEPT squamous cell carcinoma or predominantly squamous. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present in which case the patient is ineligible. (Sputum cytology alone is not acceptable)
•Must have disease that is not curative by standard methods.
•Prior adjuvant systemic chemotherapy, immunotherapy, or biological therapy is allowed, except for prior use of bevacizumab. If gemcitabine was used, more than six months must have elapsed between completion of adjuvant therapy and disease progression. Patient must be at least 14 days from previous systemic therapy (at least 30 days for investigational agents) and have recovered from the acute toxic effects of the treatment as determined by the treating physician prior to study registration. Prior therapy other than adjuvant therapy is not allowed.
•Prior radiation therapy must be completed at least 14 days of study registration and subjects must fully recover from acute toxicities as determined by the treating physician. Prior radiation to \> 25% of bone marrow is not allowed. Prior radiation therapy to the whole pelvis is not allowed.
•Disease status must be measurable or non-measurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
•ECOG Performance status of 0 or 1
•Age 18 years or greater
•Adequate organ function within 14 days of study registration including the following:
•Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, platelets ≥ 100 x 10\^9/L, hemoglobin ≥ 9 g/dL
•Hepatic: bilirubin ≤ 1.5 times the upper limit of normal (× ULN), alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 × ULN (ALP, AST, and ALT ≤ 5 × ULN is acceptable if liver has tumor involvement)

Exclusion Criteria

•Intrathoracic lung carcinoma of squamous cell histology. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible; sputum cytology alone is acceptable for inclusion. Subjects with extrathoracic-only squamous cell NSCLC are eligible. Subjects with only peripheral lung lesions of any NSCLC histology will also be eligible. A peripheral lesion is defined as a lesion in which the epicenter of the tumor is \< 2 cm from the costal or diaphragmatic pleura in a three-dimensional orientation based on each lobe of the lung and is \> 2 cm from the trachea, main and lobar bronchi.
•Pregnant (positive pregnancy test within 14 days of study enrollment) or breast-feeding. Gemcitabine and carboplatin are pregnancy category D - clear evidence of risk in pregnancy; bevacizumab is pregnancy category C - risk in pregnancy cannot be ruled out. Pregnancy testing is not required for post-menopausal (defined as absence of menses for the preceding 24 consecutive months) or surgically sterilized women.
•Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications)
•Any prior history of hypertensive crisis or hypertensive encephalopathy
•New York Heart Association (NYHA) Grade II or greater congestive heart failure
•History of stroke or transient ischemic attack within 6 months prior to study enrollment
•Clinically significant peripheral vascular disease (e.g., aortic aneurysm, aortic dissection)
•Symptomatic peripheral vascular disease
•Evidence of bleeding diathesis or coagulopathy in the absence of therapeutic anticoagulation
•Current or recent (within 10 days of enrollment) use of aspirin (\>325 mg/day) or chronic use of other NSAIDs known to inhibit platelet function Treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal)

Arms & Interventions

Patients with Stage IIIb/IV Non-Small Cell Lung Cancer

Patients treated with Gemcitabine 2000mg/m\^2 intravenously (IV) over 30 minutes, followed by Carboplatin AUC= 3 IV over 30 minutes and Bevacizumab 10 mg/kg IV over 90 minutes 1st infusion, 60 minutes 2nd infusion and 30 minutes for the following infusions. Cycles will be repeated every 2 weeks for a maximum of 6 cycles of therapy. Bevacizumab will continue to be given until disease progression.

Intervention: Gemcitabine, Carboplatin, Bevacizumab

Outcomes

Primary Outcomes

Time to Progression

Time Frame: From Enrollment Through 2 Years

Time to progression (progression free survival)is defined as the time from the start of treatment until first documented sign of disease progression or death due to any cause. For subjects who do not progress, time to progression will be censored at the time of last tumor assessment.

Secondary Outcomes

Best Overall Response by Cycle(After Cycle 4, Cycle 6 and Cycle 7 of Therapy)
Time to Best Response(From Enrollment to First Tumor Response)
Overall Survival Time(Baseline to Death)
Duration of Response(From Enrollment through Date of First Documented Disease Progression or Date of Death From Any Cause, Whichever Came First, Up to 100 Months)