Pemetrexed Disodium, Gemcitabine, and Bevacizumab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

NCT00438204 | Terminated Phase 2 Results DMC

• 4 other identifiers: CDR0000531832P30CA022453WSU-2005-008WSU-036806MP4F
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving pemetrexed disodium and gemcitabine together with bevacizumab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving pemetrexed disodium and gemcitabine together with bevacizumab works in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Conditions

Lung Cancer

Keywords

stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; adenocarcinoma of the lung; bronchoalveolar cell lung cancer; large cell lung cancer; recurrent non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  RECIST criteria for tumor progression of at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

  Up to 12 months

Secondary Outcomes (4)

• Number of Participants With Response

  Every 8 weeks, for up to 54 months

• Number of Participants With Grade 3 or Grade 4 Toxicity

  Every two weeks, for up to 54 months

• Time to Treatment Failure

  Every 8 weeks, for up to 54 months

• Overall Survival

  Every 8 weeks, for up to 54 months

Study Arms (1)

Bevacizumab, gemcitabine hydrochloride

EXPERIMENTAL

Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed disodium every 14 days Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days.

Biological: bevacizumab; Drug: gemcitabine hydrochloride; Drug: pemetrexed disodium

Interventions

bevacizumab BIOLOGICAL

Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days

Also known as: Avastin ®

Bevacizumab, gemcitabine hydrochloride

gemcitabine hydrochloride DRUG

Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days

Also known as: Gemzar ®

Bevacizumab, gemcitabine hydrochloride

pemetrexed disodium DRUG

Pemetrexed disodium 400 mg/m2 intravenously over 10 minutes every 14 days.

Also known as: Alimta®

Bevacizumab, gemcitabine hydrochloride

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic or cytologic proof of non-squamous non-small cell lung cancer (NSCLC) (adenocarcinoma, bronchioloalveolar, large cell carcinoma).
• Must have Stage IV or IIIB NSCLC. Patients with Stage IIIB must have a pleural effusion or not be candidates for treatment for locally advanced disease with chemoradiotherapy.
• Cannot have a tumor with cavitation..
• Have uni-dimensional measurable or evaluable disease. If disease is within a previous radiation port there must be documented progression.
• years of age and have a life expectancy of greater than 12 weeks.
• Must not have had prior chemotherapy for advanced disease.
• Must have an ECOG performance status of 0-1.
• With treated brain metastases are eligble. for details.
• Adequate organ function:
• Absolute neutrophil count of \> 1.5 x 109/L Platelet count \> 100,000/109/L Hemoglobin \> 8g/dl Calculated creatinine clearance \> 45mL/min using the standard Cockroft and Gault formula Hepatic: bilirubin \< 1.5 times the upper limit of normal,alkaline phosphatase, aspartate transaminase (AST) and alanine transaminase (ALT) \< 3 times upper limit of normal. Alkaline phosphatase, AST, ALT \< 5 times upper limit of normal is acceptable if liver has tumor involvement. Urine protein:creatinine ratio ≤1.0 at screening
• Patients of reproductive potential must use an approved contraceptive method during and for 3 months after study.
• Must sign an informed consent that details the investigational nature of the study according to the institutional and federal guidelines.
• Registered with the clinical trials office of the institution.

You may not qualify if:

• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
• Prior chemotherapy except for erlotinib for advanced disease.
• Uncontrolled hypertension (Blood pressure of \>150/100 mmHg )
• Unstable angina
• New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
• History of myocardial infarction within 6 months prior to day 1
• History of hemorrhagic or thrombotic stroke or other CNS bleed within 6 months prior to day 1
• Clinically significant peripheral vascular disease of 61
• Evidence of bleeding diathesis or coagulopathy. Patients must not require full dose anticoagulants for any reason.
• Known CNS disease, except for treated brain metastasis 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.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
• Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0
• Urine protein:creatinine ratio \> or = 1.0 at screening
• History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to Day 0
• Serious, non-healing wound, ulcer, or bone fracture

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0942, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Related Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung; Adenocarcinoma, Bronchiolo-Alveolar

Interventions

Bevacizumab; Gemcitabine; Pemetrexed

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Limitations and Caveats

There were no significant limitations of the trial.

Results Point of Contact

• Title: Antionette J. Wozniak, M.D., F.A.C.P.
• Organization: Barbara Ann Karmanos Cancer Institute

wozniakt@karmanos.org

(313)576-8752

Study Officials

• Antoinette J. Wozniak, MD

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 20, 2007
• First Posted: February 22, 2007
• Study Start: May 1, 2006
• Primary Completion: March 1, 2013
• Study Completion: June 1, 2016
• Last Updated: April 13, 2021
• Results First Posted: July 4, 2014

Record last verified: 2021-03

Locations

US (2)