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

• ClinicalTrials.gov Identifier: NCT00517595
• Recruitment Status: Completed
• First Posted: August 17, 2007
• Results First Posted: March 8, 2012
• Last Update Posted: March 12, 2012
• Sponsor: Accelerated Community Oncology Research Network
• Collaborators: Eli Lilly and Company; Genentech, Inc.
• Information provided by (Responsible Party): Accelerated Community Oncology Research Network

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non-Small Cell Lung Cancer	Drug: Pemetrexed and Gemcitabine plus Bevacizumab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: August 2007
• Actual Primary Completion Date: April 2011
• Actual Study Completion Date: April 2011

Arms and Interventions

Intervention Details:

• 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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.

Other Outcome Measures:

1. Progression Free Survival (PFS) by Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status [ 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. The median progression free survival is the parameter used to describe PFS. ECOG performance status describes how daily living activities of the patient are affected by disease. ECOG of 0 means the patient is fully active without restriction. ECOG of 1 means the patient is restricted in physically strenuous activity but is able to carry out light work. The investigator assigned the ECOG score at baseline (i.e., before the patient started study treatment).
2. Overall Survival (OS) by Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status [ 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. ECOG performance status describes how daily living activities of the patient are affected by disease. ECOG of 0 means the patient is fully active without restriction. ECOG of 1 means the patient is restricted in physically strenuous activity but is able to carry out light work. The investigator assigned the ECOG score at baseline (i.e., before the patient started study treatment).

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Connecticut

Medical Oncology & Hematology

Waterbury, Connecticut, United States, 06708

United States, Georgia

Augusta Oncology Associates

Augusta, Georgia, United States, 30901

Central Georgia Cancer Care

Macon, Georgia, United States, 31201

Northwest Georgia Oncology Center

Marietta, Georgia, United States, 30060

United States, Montana

Hematology Oncology Centers of the Northern Rockies

Billings, Montana, United States, 59101

United States, Ohio

Tri-County Oncology Hematology Associates

Canton, Ohio, United States, 44718

United States, Oregon

Pacific Oncology, PC

Portland, Oregon, United States, 97225

United States, Pennsylvania

Pennsylvania Oncology Hematology Associates

Philadelphia, Pennsylvania, United States, 19106

United States, Tennessee

The West Clinic

Memphis, Tennessee, United States, 38120

United States, Virginia

Cancer Specialists of Tidewater

Chesapeake, Virginia, United States, 23320

Sponsors and Collaborators

Accelerated Community Oncology Research Network

Eli Lilly and Company

Genentech, Inc.

Investigators

• Principal Investigator: Johnetta L Blakely, MD; Accelerated Community Oncology Research Network

More Information

• Responsible Party: Accelerated Community Oncology Research Network
• ClinicalTrials.gov Identifier: NCT00517595
• Other Study ID Numbers: ALJBNSCLC0602
• First Posted: August 17, 2007
• Results First Posted: March 8, 2012
• Last Update Posted: March 12, 2012
• Last Verified: March 2012

Keywords provided by Accelerated Community Oncology Research Network:

Non-Small Cell Lung Cancer

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Gemcitabine; Bevacizumab; Pemetrexed; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors