Clinical trial NCT00517595: Phase II Study Alimta and Gemzar + Avastin as First Line Chemotherapy for Elderly Patients With Stage IIIB/IV NSCLC
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer
Lead sponsor: Accelerated Community Oncology Research Network
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
name: Genentech, Inc.
First posted: 2007-08-17
Enrollment: 48
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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.
Secondary outcomes:
measure: Time to Progression (TTP)
timeFrame: TTP was measured from day 1 of treatment until time of progression (assessed every 8 weeks), assessed up to 15 months.
measure: Overall Survival (OS)
timeFrame: OS was measured from day 1 of treatment until time of death, assessed up to 20 months.
measure: Overall Response
timeFrame: Response to treatment was assessed after every 8 weeks of treatment, up to 50 weeks.
Other outcomes:
measure: Progression Free Survival (PFS) by Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: 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.
measure: Overall Survival (OS) by Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: OS was measured from day 1 of treatment until time of death, assessed up to 20 months.
Locations:
city: Waterbury
country: United States
facility: Medical Oncology & Hematology
state: Connecticut
city: Augusta
country: United States
facility: Augusta Oncology Associates
state: Georgia
city: Macon
country: United States
facility: Central Georgia Cancer Care
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Center
state: Georgia
city: Billings
country: United States
facility: Hematology Oncology Centers of the Northern Rockies
state: Montana
city: Canton
country: United States
facility: Tri-County Oncology Hematology Associates
state: Ohio
city: Portland
country: United States
facility: Pacific Oncology, PC
state: Oregon
city: Philadelphia
country: United States
facility: Pennsylvania Oncology Hematology Associates
state: Pennsylvania
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Chesapeake
country: United States
facility: Cancer Specialists of Tidewater
state: Virginia
Study officials:
affiliation: Accelerated Community Oncology Research Network
name: Johnetta L Blakely, MD
role: PRINCIPAL_INVESTIGATOR
References: