Phase II Study Alimta and Gemzar + Avastin as First Line Chemotherapy for Elderly Patients With Stage IIIB/IV NSCLC

Tracking Information
First Submitted Date ICMJE	August 16, 2007
First Posted Date ICMJE	August 17, 2007
Results First Submitted Date	October 11, 2011
Results First Posted Date	March 8, 2012
Last Update Posted Date	March 12, 2012
Study Start Date ICMJE	August 2007
Actual Primary Completion Date	April 2011 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: February 7, 2012)	Progression Free Survival (PFS) [ Time Frame: PFS was measured from day 1 of treatment until time of progression (assessed every 8 weeks) or death, whichever came first, assessed up to 15 months. ]; PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions. The median progression free survival is the parameter used to describe PFS.
Original Primary Outcome Measures ICMJE; (submitted: August 16, 2007)	The primary endpoint will be the percent of patients who are progression free (PFS) at 12 months after initiation of treatment.
Change History	Complete list of historical versions of study NCT00517595 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: March 8, 2012)	Time to Progression (TTP) [ Time Frame: TTP was measured from day 1 of treatment until time of progression (assessed every 8 weeks), assessed up to 15 months. ]Time to progression is defined as the time from treatment start until objective tumor progression. Progression is defined per RECIST criteria v1.0 as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions. The median time to progression is the parameter used to describe TTP.; Overall Survival (OS) [ Time Frame: OS was measured from day 1 of treatment until time of death, assessed up to 20 months. ]Overall survival is defined as the time from treatment start until death from any cause. The median overall survival time is used to measure OS.; Overall Response [ Time Frame: Response to treatment was assessed after every 8 weeks of treatment, up to 50 weeks. ]Response was evaluated via changes from baseline in radiological tumor measurements performed after every 4th treatment cycle and at the end of treatment or time of progression. Response was evaluated using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions.
Original Secondary Outcome Measures ICMJE; (submitted: August 16, 2007)	Secondary endpoints will be overall response rate (RECIST), overall survival, and changes from baseline in PCM scores. Also, time to progression will be evaluated as it relates to the number of cycles prior to progression and duration.
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Phase II Study Alimta and Gemzar + Avastin as First Line Chemotherapy for Elderly Patients With Stage IIIB/IV NSCLC
Official Title ICMJE	A Phase II Study of Pemetrexed and Gemcitabine Plus Bevacizumab as First Line Chemotherapy for Elderly Patients With Stage IIIB/IV Non-Small Cell Lung Cancer
Brief Summary	The primary objective is to determine the progression free survival with pemetrexed, and gemcitabine plus bevacizumab as first-line chemotherapy in elderly patients with Stage IIIB/IV non-small cell lung cancer (NSCLC). The secondary objectives are to determine the overall response rate; overall survival; chemotherapy induced toxicity profile of this combination; time to progression; and patient reported symptom burden.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Non-Small Cell Lung Cancer
Intervention ICMJE	Drug: Pemetrexed and Gemcitabine plus Bevacizumab; Bevacizumab 10 mg/kg will be given intravenously according to weight. Pemetrexed 500 mg/m^2 and gemcitabine 1500 mg/m^2 will be given intravenously according to weight and height. All agents are administered every 2 weeks.; Other Names: Pemetrexed/Alimta; Gemcitabine/Gemzar; Bevacizumab/Avastin
Study Arms	Not Provided
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: August 16, 2007)	48
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	April 2011
Actual Primary Completion Date	April 2011 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Patient provides voluntary written informed consent before performance of any study-related procedure not part of normal medical care.; Patient ≥ 65 years of age with ECOG of 0 to 1; Patient must have histologically/cytologically confirmed Stage IIIB/IV NSCLC.; Patient has measurable disease defined as at least 1 lesion that can be accurately measured in at least 1 dimension (by CT or MRI) & used to assess response as defined by RECIST criteria. Tumors within a previously irradiated field will be designated nontarget lesions.; Patient has not received radiotherapy within 2 weeks(4 weeks required for brain metastases radiotherapy)of initial chemotherapy dosing for this study, and all acute toxicities due to prior radiotherapy have resolved prior to initial chemotherapy dosing.; Patient has a negative serum pregnancy test or has undergone hysterectomy at time of enrollment.; Greater than 12 weeks life expectancy.; Patient has recovered from any recent surgery for at least 30 days & is free of active infection requiring antibiotics.; Patient must be willing/able to discontinue use of NSAIDS prior to study drug dosing.; Patient must be able to take folic acid, Vitamin B12, & dexamethasone per protocol.; Patient must exhibit no greater than Grade 1 peripheral neuropathy. Exclusion Criteria: Prior systemic or other concurrent chemo for metastatic NSCLC(Prior Tarceva is not allowed).Prior adjuvant chemo acceptable as long as > 12 months since completion and no prior pemetrexed, gemcitabine or bevacizumab.; 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.Patients with extrathoracic-only squamous cell NSCLC are eligible.Patients 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).; Hemoptysis within 1 month prior to study enrollment; Ongoing treatment with full-dose warfarin or its equivalent i.e., unfractionated and/or low molecular weight heparin.(Low dose warfarin 1 mg given for prophylaxis is allowed).; Hypersensitivity to any component of Alimta, gemcitabine &/or bevacizumab, &/or cannot tolerate folic acid, corticosteroids or Vitamin B12 supplements.; Currently/have recently taken long-acting NSAID (Ibuprofen ≤ 400 mg QID acceptable) or aspirin (>325mg/day) within 5 days of initial pemetrexed administration.; Clinically significant pericardial/pleural effusion or ascites unless able to be drained before study entry.; Presence of third space fluid which cannot be controlled by drainage.; Core biopsy/other minor surgical procedure(excluding placement of a vascular access device)within 7 days prior to study enrollment.; Active infection or fever ≥ 38.5°C within 3 days of first scheduled day of protocol treatment.; Serious, non-healing wound, ulcer, or untreated bone fracture.; NYHA Grade II or greater CHF; Inadequately controlled hypertension (defined as systolic blood pressure > 150 &/or diastolic blood pressure > 100mmHg on antihypertensive meds); Any prior history of hypertensive crisis or hypertensive encephalopathy.; History of MI, CVA, TIA, or unstable angina within 6 months of study enrollment.; Significant vascular disease (aortic aneurysm, aortic dissection or recent peripheral arterial thrombosis.); Symptomatic peripheral vascular disease; Known bleeding diathesis or coagulopathy; Presence of CNS(central nervous system) except for treated brain metastases. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging(MRI or CT)during the screening period.Anticonvulsants(stable dose)are allowed.Treatment for brain metastases may include whole brain radiotherapy(WBRT),radiosurgery(RS;Gamma Knife,LINAC,or equivalent)or a combination as deemed appropriate by the treating physician.Radiotherapy must be completed at least 4 weeks prior to study enrollment and all acute radiotherapy toxicities resolved.Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.; A major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study.; Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrollment.; History of prior malignancy within the past 5 years except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current prostate specific antigen of < 1.0 mg/dL on 2 successive evaluations, at least 3 months apart, with the most recent evaluation no more than 4 weeks prior to entry.; Have received radiotherapy to more than 25% of their bone marrow.; Receiving concurrent investigational therapy or has received investigational therapy within 30 days of the first scheduled day of protocol treatment; Pregnant/lactating.; Any other medical condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate/participate in the study, or interfere with interpretation of the results.; History of allogeneic transplant.; Known HIV infection or Hepatitis B or C.
Sex/Gender	Sexes Eligible for Study: All
Ages	65 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00517595
Other Study ID Numbers ICMJE	ALJBNSCLC0602
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Accelerated Community Oncology Research Network
Study Sponsor ICMJE	Accelerated Community Oncology Research Network
Collaborators ICMJE	Eli Lilly and Company; Genentech, Inc.
Investigators ICMJE	Principal Investigator: Johnetta L Blakely, MD Accelerated Community Oncology Research Network
PRS Account	Accelerated Community Oncology Research Network
Verification Date	March 2012
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP