Lung CancerPhase 2NCT00438204
Pemetrexed Disodium, Gemcitabine, and Bevacizumab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
A Phase 2 study testing bevacizumab, gemcitabine hydrochloride and pemetrexed disodium in people with Lung Cancer, run by Barbara Ann Karmanos Cancer Institute at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- bevacizumab, gemcitabine hydrochloride and pemetrexed disodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2006to Jun 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 18 years of age and have a life expectancy of greater than 12 weeks.
- Must not have had prior chemotherapy for advanced disease.
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- 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.
Who cannot join
- 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
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- 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
- Evidence of cavitation in the tumor.
- Intrathoracic 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 unacceptable.
- Extrathoracic-only squamous cell NSCLC are eligible. Patients with only peripheral lung lesions (of any NSCLC histology) will also be eligible.
- History of hemoptysis (bright red blood of 1/2 teaspoon or more within 28 days of registration or clinical history of > Grade 2
- Clinically significant effusions that cannot be drained
- Inability to comply with study and/or follow-up procedures
- Previous or concurrent malignancies with the exception of adequately treated squamous cell or basal cell carcinoma of the skin, in situ carcinoma of the cervix, or any other malignancy treated and in clinical remission for more than 3 years.
- Prior radiation therapy to the target lesion, unless the lesion is clearly progressing and the interval between the most recent radiation therapy and enrollment is at least 4 weeks.
- Pregnancy or lactating females. All pre-menopausal women should have a negative urine pregnancy test prior to enrollment. All patients of reproductive potential should agree to use an effective contraceptive method.
- Serious concomitant systemic disorders (including oncologic emergencies) incompatible with the study (at the discretion of the investigator).
- Inability to interrupt non-steroidal anti-inflammatory agents 2 days before, the day of, and 2 days after the dose of pemetrexed.
- Disease which cannot be radiologically imaged.
- Inability to take dexamethasone, folic acid or vitamin B12 administration.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109-0942
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201-1379
About this study
Official title: A Phase II Trial of Pemetrexed, Gemcitabine, and Bevacizumab Every Two Weeks in Chemotherapy-Naive Patients With Stages IIIB/IV Non- Squamous, Non-Small Cell Lung Cancer (NSCLC)
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.
Read the detailed description
OBJECTIVES:
Primary
- Determine the efficacy of pemetrexed disodium, gemcitabine hydrochloride, and bevacizumab in chemotherapy-naïve patients with stage IIIB or IV nonsquamous cell non-small cell lung cancer.
Secondary
- Determine the response rate in patients treated with this regimen.
- Determine the time to treatment failure in patients treated with this regimen.
- Determine the overall survival of patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
OUTLINE: Patients receive pemetrexed disodium IV over 10 minutes, gemcitabine hydrochloride IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 14 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients may then receive bevacizumab alone in the absence of disease progression or unacceptable toxicity.
After the completion of study treatment, patients are followed periodically for 6 months.
PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.
- Conditions
- Lung Cancer
- Being tested
- bevacizumab, gemcitabine hydrochloride, pemetrexed disodium
- 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
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Adenocarcinoma of Lung, Adenocarcinoma, Bronchiolo-Alveolar
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabBiological
Also called Avastin ®
Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days
Also called Gemzar ®
Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days
pemetrexed disodiumDrug
Also called Alimta®
Pemetrexed disodium 400 mg/m2 intravenously over 10 minutes every 14 days.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: bevacizumab; Drug: gemcitabine hydrochloride; Drug: pemetrexed disodium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 12 months
Secondary outcomes (4)
Number of Participants With Response
The rate of response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Every 8 weeks, for up to 54 months
Number of Participants With Grade 3 or Grade 4 Toxicity
Grade 3/4 toxicity according to the NCI Common Toxicity Criteria v3.0 .
Measured: Every two weeks, for up to 54 months
Time to Treatment Failure
Time to treatment failure using the Kaplan-Meier method.
Measured: Every 8 weeks, for up to 54 months
Overall Survival
Overall survival using the Kaplan-Meier method.
Measured: Every 8 weeks, for up to 54 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2007 (estimated)
- Study startMay 2006
- Primary completionMar 2013
- Study completionJun 2016
Why it stopped: All data collection has completed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barbara Ann Karmanos Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Antoinette J. Wozniak, Barbara Ann Karmanos Cancer Institute
- Investigators
- Antoinette J. Wozniak, MD, Principal investigator, Barbara Ann Karmanos Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00438204
- Sponsor's protocol ID
- CDR0000531832
- Other IDs
- P30CA022453, WSU-2005-008, WSU-036806MP4F
- Status last verified
- Mar 2021
- First submitted
- 20 Feb 2007
- Last updated
- 13 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Pemetrexed, Gemcitabine, and Bevacizumab Every Two Weeks in Chemotherapy-Naive Patients With Stages IIIB/IV Non- Squamous, Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT00438204
- Acronym / sponsor ID
- CDR0000531832
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: All data collection has completed.
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Barbara Ann Karmanos Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2006
- Primary completion
- Mar 2013 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 22 Feb 2007 (estimated)
- Results
- Posted 4 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- Determine the efficacy of pemetrexed disodium, gemcitabine hydrochloride, and bevacizumab in chemotherapy-naïve patients with stage IIIB or IV nonsquamous cell non-small cell lung cancer.
Secondary
- Determine the response rate in patients treated with this regimen.
- Determine the time to treatment failure in patients treated with this regimen.
- Determine the overall survival of patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
OUTLINE: Patients receive pemetrexed disodium IV over 10 minutes, gemcitabine hydrochloride IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 14 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients may then receive bevacizumab alone in the absence of disease progression or unacceptable toxicity.
After the completion of study treatment, patients are followed periodically for 6 months.
PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab, gemcitabine hydrochloride | Experimental | Biological: bevacizumab, Drug: gemcitabine hydrochloride, Drug: pemetrexed disodiumBevacizumab 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
- 18 years of age and have a life expectancy of greater than 12 weeks.
Key exclusion criteria (28 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bevacizumabAlso: Avastin ®Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days | Biological | Bevacizumab, gemcitabine hydrochloride |
| gemcitabine hydrochlorideAlso: Gemzar ®Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days | Drug | Bevacizumab, gemcitabine hydrochloride |
| pemetrexed disodiumAlso: Alimta®Pemetrexed disodium 400 mg/m2 intravenously over 10 minutes every 14 days. | Drug | Bevacizumab, gemcitabine hydrochloride |
Primary outcome
Progression-free Survival (PFS)
Time frame: Up to 12 months
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).
4 secondary outcomes
Number of Participants With Response
Time frame: Every 8 weeks, for up to 54 months
Number of Participants With Grade 3 or Grade 4 Toxicity
Time frame: Every two weeks, for up to 54 months
Time to Treatment Failure
Time frame: Every 8 weeks, for up to 54 months
Overall Survival
Time frame: Every 8 weeks, for up to 54 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Clinical trial summary from the National Cancer Institute's PDQ® databaseLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antoinette J. Wozniak, MD principal investigator
Barbara Ann Karmanos Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bevacizumab, gemcitabine hydrochloride and pemetrexed disodium in people with Lung Cancer, run by Barbara Ann Karmanos Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2021.