First-Line Treatment of A Comparison of 2 Treatments in Elderly Patients With Advanced NSCLC

A Randomized Phase II Trial of Pemetrexed/Gemcitabine/Bevacizumab or Pemetrexed/Carboplatin/Bevacizumab in the First-Line Treatment of Elderly Patients With Advanced Non-Small Cell Lung Cancer

This trial will look at 2 different drug combinations that have well known safety profiles and are known to be active against non small cell lung cancer and combine them with bevacizumab, an experimental drug that has shown effectiveness when added to other drug combinations for advanced non-small cell lung cancer. The primary objective in this study is to see how well this combination of drugs keeps the cancer from getting worse in this elderly population of non-small cell lung cancer patients.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Pemetrexed; Drug: Gemcitabine; Drug: Bevacizumab; Drug: Carboplatin

Detailed Description

Patients in this study will be assigned to one of 2 treatment groups. The selection of the treatment groups will be done randomly by a computer.

The first group, Cohort A, will receive bevacizumab 10mg/kg by vein over 30-90 minutes followed by pemetrexed 500 mg/m2 by vein over 10 minutes followed by gemcitabine 1500 mg/m2 by vein over 30-60 minutes. This regimen will be given on day 1 and day 15 of each treatment cycle. Each cycle is 28 days long. As long as their disease does not worsen patients can receive up to a maximum of 6 cycles of this combination chemotherapy. Following that they can receive bevacizumab alone once every 2 weeks as long as their disease does not worsen.

The second group, Cohort B, will receive bevacizumab 15mg/kg by vein over 30-90 minutes followed by pemetrexed 500 mg/m2 by vein over approximately 10 minutes followed by carboplatin AUC=5 by vein over 30-60 minutes. This regimen will be given on day 1 of each treatment cycle. Each cycle is 21 days long. As long as their disease does not worsen patients can receive up to a maximum of 6 cycles of this combination chemotherapy. Following that they can receive bevacizumab alone once every 3 weeks as long as their disease does not worsen.

In both regimens vitamin B12 injections and Folic Acid pills will be given to reduce the occurrence of side effects from the treatment.

Each patient's disease will be evaluated at intervals by the proper scans or X-rays to see how well the cancer is responding to the treatment.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Northeast Alabama Regional Medical Center
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Clinic
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Lakeland, Florida, United States, 33805
      • Watson Clinic Center for Cancer Care and Research
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
    • Marietta, Georgia, United States, 30060
      • Wellstar Cancer Research
  • Indiana
    • Terre Haute, Indiana, United States, 47802
      • Providence Medical Group
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Graves-Gilbert Clinic
    • Louisville, Kentucky, United States, 40207
      • Consultants in Blood Disorders and Cancer
  • Maine
    • Portland, Maine, United States, 04101
      • Mercy Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Grand Rapids Clinical Oncology Program
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Cancer Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Cancer Care of Western North Carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Regional Medical Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Oncology Hematology Associates
    • Chattanooga, Tennessee, United States, 37404
      • Associates in Hematology Oncology
    • Nashville, Tennessee, United States, 37023
      • Tennessee Oncology, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed non-small cell bronchogenic carcinoma, (adenocarcinoma, or large cell carcinoma)
• Patients who have newly diagnosed unresectable stage III or stage IV disease are eligible.
• Must be at least 70 years of age
• Must have measurable disease by CT scan
• Must be able to be up and about and care for themselves
• May not have received prior treatment for stage III or IV disease
• Must have adequate white and red blood cells and platelets.
• Must be able to take Vitamin B12, Folic Acid and dexamethasone as stated in the study
• Must be able to understand the nature of this study and give written informed consent
• Adequate liver and kidney function

Exclusion Criteria:

• Past or current history of cancer with the exception of treated non- melanoma skin cancer or carcinoma in-situ of the cervix, or other cancers cured by local therapy alone and have been disease free for five years
• Female patients who are pregnant or are lactating are ineligible
• History of unstable angina or myocardial infarction within 6 months prior to beginning bevacizumab
• Brain metastasis - cancer that has spread to the brain
• Major surgical procedure, open biopsy, or significant traumatic injury within 6 weeks of beginning bevacizumab or anticipation of need for major surgical procedure during the course of the study
• Full-dose oral or by vein anticoagulation or receiving anti-clotting therapy within 10 days of starting treatment
• Serious nonhealing wound, ulcer, or bone fracture
• Bleeding or clotting disorders
• Uncontrolled high blood pressure or serious heart arrhythmia requiring medication
• History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 6 months prior to beginning bevacizumab
• Chronic non-steroidal anti-inflammatory use is not allowed on study
• History of stroke or TIAs within the last 6 months

Please Note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Cohort A, will receive bevacizumab 10mg/kg by vein over 30-90 minutes followed by pemetrexed 500 mg/m2 by vein over 10 minutes followed by gemcitabine 1500 mg/m2 by vein over 30-60 minutes. This regimen will be given on day 1 and day 15 of each treatment cycle. Each cycle is 28 days long. As long as their disease does not worsen patients can receive up to a maximum of 6 cycles of this combination chemotherapy. Following that they can receive bevacizumab alone once every 2 weeks as long as their disease does not worsen.	Drug: Pemetrexed; pemetrexed 500 mg/m2; Other Names: Alimta; Drug: Gemcitabine; gemcitabine 1500 mg/m2; Other Names: Gemzar; Drug: Bevacizumab; bevacizumab 10mg/kg bevacizumab 15mg/kg; Other Names: Avastin
Experimental: Cohort B; Cohort B, will receive bevacizumab 15mg/kg by vein over 30-90 minutes followed by pemetrexed 500 mg/m2 by vein over approximately 10 minutes followed by carboplatin AUC=5 by vein over 30-60 minutes. This regimen will be given on day 1 of each treatment cycle. Each cycle is 21 days long. As long as their disease does not worsen patients can receive up to a maximum of 6 cycles of this combination chemotherapy. Following that they can receive bevacizumab alone once every 3 weeks as long as their disease does not worsen.	Drug: Pemetrexed; pemetrexed 500 mg/m2; Other Names: Alimta; Drug: Bevacizumab; bevacizumab 10mg/kg bevacizumab 15mg/kg; Other Names: Avastin; Drug: Carboplatin; carboplatin AUC=5; Other Names: Paraplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Progression (TTP), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease	Time to Progression (TTP) is defined as the interval between the date of treatment initiation and the date of progressive disease. Progression is defined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0). Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or unequivocal progression of non-target lesions or the appearance of one or more new lesions.	From the date of treatment initiation until the date of first documented PD or date of last study contact or date of other therapy begins up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment	Overall response rate (ORR) is defined as the percentage of patients who have a partial or complete response to therapy. Responses were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.0). Complete Response: Disappearance of all target lesions, and disappearance of all non-target lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter of target lesions (taking as reference the baseline sum of longest diameters)	From date of treatment initiation to end of study treatment up to 18 months
Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death	OS is defined as the time from the date of study entry until the date of death due to any cause. In the absence of confirmation of death or lack of data beyond follow-up period, the survival time was censored to the last date the participant was known to be alive.	From date of study entry until the date of death from any cause or the date the patient was last known alive, up to 18 months

Collaborators and Investigators

• Sponsor: SCRI Development Innovations, LLC
• Collaborators: Eli Lilly and Company; Genentech, Inc.
• Investigators: Principal Investigator: David R Spigel, MD, SCRI Development Innovations, LLC

Publications and helpful links

General Publications

• Spigel DR, Hainsworth JD, Shipley DL, Ervin TJ, Kohler PC, Lubiner ET, Peyton JD, Waterhouse DM, Burris HA 3rd, Greco FA. A randomized phase II trial of pemetrexed/gemcitabine/bevacizumab or pemetrexed/carboplatin/bevacizumab in the first-line treatment of elderly patients with advanced non-small cell lung cancer. J Thorac Oncol. 2012 Jan;7(1):196-202. doi: 10.1097/JTO.0b013e3182307efe.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: April 3, 2007
• First Submitted That Met QC Criteria: April 3, 2007
• First Posted (Estimate): April 4, 2007

Study Record Updates

• Last Update Posted (Actual): May 3, 2022
• Last Update Submitted That Met QC Criteria: April 8, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Non Small Cell Lung Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Folic Acid Antagonists; Gemcitabine; Carboplatin; Bevacizumab; Pemetrexed
• Other Study ID Numbers: SCRI LUN 139