Lung Cancer, Small CellPhase 2NCT01313663
A Study to Evaluate Pazopanib in Comparison to Pemetrexed in Maintenance Setting in Non-progressing Subjects With Metastatic Stage IVA and IVB Non-squamous Non-small Cell Lung Cancer (NSCLC) Population
A Phase 2 study testing pazopanib and pemetrexed in people with Lung Cancer, Small Cell, run by GlaxoSmithKline at 25 sites in United States.
Trial summary
This is a Phase II, randomized, open-label, multi-center study in advanced (Stage IVA and IVB subjects per the International Association for the Study of Lung Cancer (IASLC) 2009 Lung cancer staging schema) non-squamous NSCLC subjects comparing pazopanib relative to pemetrexed in the maintenance setting. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Small Cell
- What is being tested?
- pazopanib and pemetrexed
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 25 sitesUnited States
- Study dates
- Feb 2011to Jul 2012
- 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
- Signed written Informed Consent.
- Subjects must complete 4 to 6 cycles of chemotherapy with carboplatin + pemetrexed or cisplatin + pemetrexed and have had SD, PR or CR at the time of screening/enrolment as the best response.
- Prior surgery and/or localized irradiation for NSCLC is permitted as long as it was a minimum of 4 weeks before entering the study. Subjects with recurrence after previous NSCLC that has been treated with surgery and adjuvant chemotherapy or a radio-chemotherapy regimen with curative intent are eligible, provided 1 year has passed since this treatment ended.
- Histologically or cytologically confirmed diagnosis of predominantly non-squamous cell Stage IVA Wet (with cytology positive Malignant Pleural Effusion (MPE)) or Stage IVB (metastatic) NSCLC.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of at least 12 weeks.
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- Must have measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST). A measurable lesion is defined as a lesion that can be accurately measured in at least one dimension with the longest diameter ≥ 20 mm using conventional techniques, or ≥ 10 mm with spiral computed tomography (CT) scan.
- Able to swallow and retain oral medication.
- Adequate organ system function.
- Women of childbearing potential must have a negative pregnancy test within <= 7 days prior to administration or dispensing of study treatment and agree to use effective contraception.
- Age ≥ 18 years of legal age of consent if different from 18 years.
Who cannot join
- History of active or any other malignancy other than lung cancer in the 2 yrs prior to the first dose of study drug other than NSCLC. Exception: Subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
- History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti- seizure medications for 4 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases.
- Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
- Active peptic ulcer disease
- Known intraluminal metastatic lesion/s with risk of bleeding
- Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
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- History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment
- Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
- Malabsorption syndrome Major resection of the stomach or small bowel
- Presence of uncontrolled infection.
- Corrected QT interval (QTc) > 480 msecs using Bazett's formula
- History of any one or more of the following cardiovascular conditions within the past 6 months:
- Cardiac angioplasty or stenting Myocardial infarction Unstable angina Coronary artery bypass graft surgery Symptomatic peripheral vascular disease Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA).
- Poorly controlled hypertension, defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of
- 90mmHg.
- Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Blood pressure (BP) must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment must be <140/90 mmHg in order for a subject to be eligible for the study.
- History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti- coagulating agents for at least 6 weeks are eligible.
- Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).
- Evidence of active bleeding or bleeding diathesis.
- Recent hemoptysis (>=½ teaspoon of red blood within 8 weeks before first dose of study drug).
- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels (Note: tumor abutting the vessel is acceptable, but contiguous tumor and vessel is not; CT with contrast is strongly recommended to evaluate such lesions).
- Any serious and/or unstable pre-existing medical, psychiatric, or other condition that would make the subject inappropriate for study participation including any serious condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
- Use of any prohibited medication within the timeframes listed in the protocol.
- Prior use of an investigational agent within 28 days or 5 half-lives, whichever is longer, prior the first dose of study drug.
- Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 (except the value for hemoglobin; see Table 1) and/or that is progressing in severity, except alopecia.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib and/or pemetrexed.
- Inability to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) 2 days before, the day of, and 2 days after the dose of pemetrexed. If a subject is taking an NSAID (COX-2 inhibitors included) or salicylate with a long half-life (e.g.
- naproxen, piroxicam, diflusinal, nabumetone, rofecoxib, or celecoxib) it should not be taken 5 days before, the day of, and 2 days after the dose of pemetrexed.
- Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone.
- Have clinically significant third-space fluid collections (e.g., ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to Day 1, Cycle 1.
- Treatment with any of the following anti-cancer therapies:
- radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
GSK Investigational Site
Ames, Iowa, 50010
GSK Investigational Site
Bedford, Texas, 76022
GSK Investigational Site
Charleston, South Carolina, 29425
GSK Investigational Site
Chattanooga, Tennessee, 37421
GSK Investigational Site
Columbia, Missouri, 65201
GSK Investigational Site
Dallas, Texas, 75230
GSK Investigational Site
Dallas, Texas, 75231
GSK Investigational Site
Dallas, Texas, 75246
GSK Investigational Site
Everett, Washington, 98201
GSK Investigational Site
Fargo, North Dakota, 58103
GSK Investigational Site
Garland, Texas, 75042
GSK Investigational Site
Houston, Texas, 77090
GSK Investigational Site
Indianapolis, Indiana, 46219
GSK Investigational Site
Las Vegas, Nevada, 89128
GSK Investigational Site
Latham, New York, 12110
GSK Investigational Site
Mesquite, Texas, 75150
GSK Investigational Site
Overland Park, Kansas, 66210
GSK Investigational Site
Pikeville, Kentucky, 41501
GSK Investigational Site
Raleigh, North Carolina, 27607
GSK Investigational Site
San Marcos, Texas, 78666
GSK Investigational Site
Skokie, Illinois, 60076
GSK Investigational Site
Skokie, Illinois, 60077
GSK Investigational Site
Tucson, Arizona, 85704
GSK Investigational Site
Tyler, Texas, 75702
GSK Investigational Site
Vancouver, Washington, 98684
About this study
Official title: A Randomized, Open-label, Phase II, 2-arm Multi-center Trial Comparing Maintenance Therapy With Pazopanib or Pemetrexed in Non-progressing Subjects With Metastatic Stage IVA and IVB Non-squamous Non-small Cell Lung Cancer (NSCLC) After Induction Therapy With Carboplatin + Pemetrexed or Cisplatin + Pemetrexed
This is a Phase II, randomized, open-label, multi-center study in advanced (Stage IVA and IVB subjects per the International Association for the Study of Lung Cancer (IASLC) 2009 Lung cancer staging schema) non-squamous NSCLC subjects comparing pazopanib relative to pemetrexed in the maintenance setting. Subjects should have completed 4-6 cycles of induction therapy with carboplatin + pemetrexed or cisplatin + pemetrexed and have had Stable Disease (SD), Partial Response (PR) or Complete Response (CR) as the best response to be enrolled into the study. The primary objective is to estimate the hazard ratio of progression free survival (PFS) in advanced NSCLC subjects given maintenance therapy of pazopanib (Arm A) relative to pemetrexed (Arm B). The secondary objectives are: overall survival, response rates, safety and tolerability. A total of approximately 200 subjects will be enrolled and randomized in a 1:1 ratio. Safety and efficacy assessments will be regularly performed on all subjects.
- Conditions
- Lung Cancer, Small Cell
- Being tested
- pazopanib, pemetrexed
- Keywords
- GW786034, non-small cell lung cancer, NSCLC, pemetrexed, pazopanib
- Medical subject headings
- Small Cell Lung Carcinoma, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pazopanibDrug
oral agent, administered at 800 mg daily (400 mg tablets x 2). Dose can be reduced, interrupted or discontinued due to adverse events or intolerance
pemetrexedDrug
pemetrexed IV 500 mg/m2 once every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Pazopanib | Experimental | oral agent, administered at 800 mg daily (400 mg tablets x 2). Dose can be reduced, interrupted or discontinued due to adverse events or intolerance Receives: Drug: pazopanib |
| Pemetrexed | Active comparator | pemetrexed IV 500 mg/m2 once every 3 weeks Receives: Drug: pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
PFS is defined as the interval between the date of randomization and the first documented sign of investigator-assessed (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) disease progression (PD) or death, whichever occurs first. The date of documented PD is the date of lesion evaluation in the case of radiological PD and the date of symptomatic cancer progression in the case of symptomatic progression (radiological confirmation is required). PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. If the participant received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS was to be censored at the last adequate assessment (LAA) prior to the initiation of therapy. Otherwise, if the participant did not have a documented date of progression or death, PFS was to be censored at the date of the LAA.
Measured: From randomization until the first documented sign of investigator-assessed disease progression or death, whichever occurred first (average of 10 study weeks)
Secondary outcomes (14)
Overall Survival
Overall survival is defined as the interval between the date of randomization and the date of death from any cause.
Measured: From randomization until disease progression or death (up to Study Week 78)
Number of Participants (Par.) With the Indicated Best Overall Response
A par. was defined as a responder if s/he sustained a CR (The disappearance of all target lesions. Any pathological lymph node must be less than 10 millimeters [mm] in the short axis) or PR (At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters) that was confirmed after >=28 days. Response was evaluated by an investigator per RECIST, version 1.1. A par. without a post-Baseline assessment was considered a non-responder. Stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started). To qualify as a best response of SD, a response of SD had to be observed >=12 weeks after randomization. A par. who was not evaluable had no scans at all or did not have a confirmatory scan.
Measured: From randomization until the time of the first documented evidence of a confirmed complete response (CR) or partial response (PR) (average of 10 weeks)
Number of Participants With Any Non-serious On-therapy Adverse Event (AE: Occurring in >=5% Participants in Any Treatment Arm) and Serious Adverse Event (SAE)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. In addition, all Grade 4 laboratory abnormalities and other medically important events that require medical or surgical intervention to prevent one of the outcomes listed previously are considered to be SAEs. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Measured: From the time the first dose of study treatment was administered until 28 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (up to Study Week 55)
Time on Study Treatment (Pazopanib), as a Measure of Extent of Exposure
Time on study treatment, as a measure of extent of exposure, was assessed in all participants who received pazopanib. Time on study treatment was not measured in participants receiving pemetrexed. For these participants, extent of exposure was measured as the mean number of dosing cycles and dose intensity. See the outcome measures entitled "Mean number of dosing cycles, as a measure of extent of exposure" and "Average dose of pemetrexed for all cycles, as a measure of extent of exposure," respectively, for pemetrexed data.
Measured: From the first day to the last day of treatment (average of 8 weeks)
Mean Daily Dose, as a Measure of Extent of Exposure
Mean daily dose, as a measure of extent of exposure, was assessed in all participants who received pazopanib. Mean daily dose was not measured in participants receiving pemetrexed. For these participants, extent of exposure was measured as the mean number of dosing cycles and dose intensity. See the outcome measures entitled "Mean number of dosing cycles, as a measure of extent of exposure" and "Average dose of pemetrexed for all cycles, as a measure of extent of exposure," respectively, for pemetrexed data.
Measured: From the first day to the last day of treatment (average of 8 weeks)
Mean Number of Pemetrexed Dosing Cycles, as a Measure of Extent of Exposure
Duration of therapy/time on study treatment, measured as the mean number of pemetrexed dosing cycles as a measure of extent of exposure, was assessed in all participants who received pemetrexed. The mean number of dosing cycles was not measured in participants receiving pazopanib. For these participants, extent of exposure was measured as the time on study treatment and mean daily dose. See the outcome measures entitled "Time on study treatment (pazopanib), as a measure of extent of exposure" and "Mean daily dose, as a measure of extent of exposure," respectively, for pazopanib data.
Measured: From the time the first dose of study treatment was administered until discontinuation of the study or death (average of 16 weeks)
Average Dose of Pemetrexed for All Cycles, as a Measure of Extent of Exposure
The average dose of pemetrexed for all cycles, as a measure of extent of exposure, was assessed in all participants who received pemetrexed. The average dose was not measured in participants receiving pazopanib. For these participants, extent of exposure was measured as the time on study treatment and mean daily dose. See the outcome measures entitled "Time on study treatment (pazopanib), as a measure of extent of exposure" and "Mean daily dose, as a measure of extent of exposure," respectively, for pazopanib data.
Measured: From the time the first dose of study treatment was administered until discontinuation of the study or death (average of 16 weeks)
Number of Participants With Any AE (Serious or Non-serious) Leading to Withdrawal From Study Treatment
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. In addition, all Grade 4 laboratory abnormalities and other medically important events that require medical or surgical intervention to prevent one of the outcomes listed previously are considered to be SAEs. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs. A participant cold have been withdrawn fom study treatment due to an SAE or AE.
Measured: From the time the first dose of study treatment was administered until withdrawal from study treatment (up to Study Week 55)
Number of Participants With Any On-therapy AE (Serious or Non-serious) Leading to Dose Reductions (DRs) or Interruptions/Delays in the Study
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. In addition, all Grade 4 laboratory abnormalities and other medically important events that require medical or surgical intervention to prevent one of the outcomes listed previously are considered to be SAEs. Refer to the general Adverse AE/SAE module for a complete list of AEs/SAEs. Management of AEs may require DRs/interruptions in study treatment. If necessary, the pazopanib dose should be reduced stepwise by 200 mg at each step. DRs for pemetrexed were 50-75% of prior dose based on the toxicity leading to DR.
Measured: From the time the first dose of study treatment was administered until discontinuation of treatment (up to Study Week 55)
Number of Participants With the Indicated Worst-case Change From Baseline in Blood Pressure
Systolic and diastolic blood pressure (BP) were measured. Categories correspond to the following Common Terminology Criteria for Adverse Events (CTCAE) grades: normal, <120/80 millimeters of mercury (mmHg); prehypertension, 120-139/80-89 mmHg, warranting intervention in participants with high risk; stage I hypertension, 140-159/90-99 mmHg, warranting intervention; and stage II hypertension >/=160/100, warranting immediate attentive intervention to prevent acute symptoms. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Participants with a missing Baseline value were assumed to have a Baseline value of <120 for systolic BP (SBP) and <80 for diastolic BP (DBP).
Measured: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)
Number of Participants With a Increase From Baseline in Bazett's QTc at the Indicated Time Points
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In clinical studies with pazopanib, events of QT prolongation have occurred.
Measured: Baseline; Week 6; Week 15; every 9 weeks in the first 6 months; every 12 weeks in the next 6 months; and, after 1 year, every 6 months (up to Study Week 55)
Number of Participants With a Change From Baseline Grade to Grade 3 and 4 for the Indicated Clinical Laboratory Parameters
Hematology and clinical chemistry data were summarized according to National Cancer Institutes (NCI) CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3, Severe; Grade 4, Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Participants with missing Baseline grades were assumed to have a Baseline grade of 0. Lymphocyte count increased: Grade 3, <500 - 200/millimeters cubed (mm^3); <0.5 - 0.2x 10e9/Liters (L); Grade 4, <200/mm^3; <0.2x 10e9/L. Lymphocyte count decreased: Grade 3, >20000/mm^3; Grade 4, NA. Hyperglycemia; Grade 3, >250 - 500 milligrams per deciliter (mg/dL); >13.9 - 27.8 millimoles per Liter (mmol/L); hospitalization indicated; Grade 4, >500 mg/dL; >27.8 mmol/L; life-threatening consequences. Hypophosphatemia (inorganic phosphorus): Grade 3, <2.0 - 1.0 mg/dL, <0.6 - 0.3 mmol/L; Grade 4, <1.0 mg/dL, <0.3 mmol/L, life-threatening consequences.
Measured: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)
Number of Participants With the Indicated Grade Changes From Baseline Grade in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk. Phos.), and Total Bilirubin (TB)
The laboratory parameters AST, ALT, Alk. Phos., and TB were summarized according to NCI CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3, Severe; Grade 4, Life-threatening or disabling; Grade 5, Death. Data are presented for any grade increase, increase to Grade 3, and increase to Grade 4. Participants with missing Baseline grades were assumed to have a Baseline grade of 0. AST/ALT: Grade 1, >upper limit of normal (ULN) - 3.0x ULN; Grade 2, >3.0 to 5.0x ULN; Grade 3, >5.0 - 20.0x ULN; Grade 4, >20.0x ULN; Grade 5, not available (NA). Alk. Phos.: Grade 1, >ULN - 2.5x ULN; Grade 2, >2.5 - 5.0x ULN; Grade 3, >5.0 - 20.0x ULN; Grade 4, >20.0x ULN; Grade 5, NA. TB: Grade 1, >ULN - >1.5x ULN; Grade 2, >1.5 - 3.0x ULN; Grade 3, >3.0 - 10.0x ULN; Grade 4, >10.0x ULN; Grade 5, NA.
Measured: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)
Number of Participants With the Indicated Changes From Baseline Value in Lactate Dehydrogenase (LDH)
Change from Baseline in the laboratory parameter LDH was assessed as "decrease to low," "change to normal" of "no change," and "increase to high." Participants with missing Baseline values were assumed to have a normal Baseline value. There is no standard normal range for LDH.
Measured: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2011 (estimated)
- Study startFeb 2011
- Primary completionJul 2012
- Study completionJul 2012
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 Cancer, Small CellStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01313663
- Sponsor's protocol ID
- 113758
- Status last verified
- Oct 2013
- First submitted
- 27 Jan 2011
- Last updated
- 27 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label, Phase II, 2-arm Multi-center Trial Comparing Maintenance Therapy With Pazopanib or Pemetrexed in Non-progressing Subjects With Metastatic Stage IVA and IVB Non-squamous Non-small Cell Lung Cancer (NSCLC) After Induction Therapy With Carboplatin + Pemetrexed or Cisplatin + Pemetrexed
- ClinicalTrials.gov ID
- NCT01313663
- Acronym / sponsor ID
- 113758
- Conditions
- Lung Cancer, Small Cell
- Keywords
- GW786034, non-small cell lung cancer, NSCLC, pemetrexed, pazopanib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 20 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Feb 2011
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 14 Mar 2011 (estimated)
- Results
- Posted 29 Apr 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase II, randomized, open-label, multi-center study in advanced (Stage IVA and IVB subjects per the International Association for the Study of Lung Cancer (IASLC) 2009 Lung cancer staging schema) non-squamous NSCLC subjects comparing pazopanib relative to pemetrexed in the maintenance setting. Subjects should have completed 4-6 cycles of induction therapy with carboplatin + pemetrexed or cisplatin + pemetrexed and have had Stable Disease (SD), Partial Response (PR) or Complete Response (CR) as the best response to be enrolled into the study. The primary objective is to estimate the hazard ratio of progression free survival (PFS) in advanced NSCLC subjects given maintenance therapy of pazopanib (Arm A) relative to pemetrexed (Arm B). The secondary objectives are: overall survival, response rates, safety and tolerability. A total of approximately 200 subjects will be enrolled and randomized in a 1:1 ratio. Safety and efficacy assessments will be regularly performed on all subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pazopanib | Experimental | Drug: pazopaniboral agent, administered at 800 mg daily (400 mg tablets x 2). Dose can be reduced, interrupted or discontinued due to adverse events or intolerance |
| Pemetrexed | Active comparator | Drug: pemetrexedpemetrexed IV 500 mg/m2 once every 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Signed written Informed Consent.
- Subjects must complete 4 to 6 cycles of chemotherapy with carboplatin + pemetrexed or cisplatin + pemetrexed and have had SD, PR or CR at the time of screening/enrolment as the best response.
- Prior surgery and/or localized irradiation for NSCLC is permitted as long as it was a minimum of 4 weeks before entering the study. Subjects with recurrence after previous NSCLC that has been treated with surgery and adjuvant chemotherapy or a radio-chemotherapy regimen with curative intent are eligible, provided 1 year has passed since this treatment ended.
- Histologically or cytologically confirmed diagnosis of predominantly non-squamous cell Stage IVA Wet (with cytology positive Malignant Pleural Effusion (MPE)) or Stage IVB (metastatic) NSCLC.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (32 listed)
- History of active or any other malignancy other than lung cancer in the 2 yrs prior to the first dose of study drug other than NSCLC. Exception: Subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
- History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti- seizure medications for 4 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases.
- Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
- Active peptic ulcer disease
- Known intraluminal metastatic lesion/s with risk of bleeding
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 |
|---|---|---|
| pazopaniboral agent, administered at 800 mg daily (400 mg tablets x 2). Dose can be reduced, interrupted or discontinued due to adverse events or intolerance | Drug | Pazopanib |
| pemetrexedpemetrexed IV 500 mg/m2 once every 3 weeks | Drug | Pemetrexed |
Primary outcome
Progression Free Survival (PFS)
Time frame: From randomization until the first documented sign of investigator-assessed disease progression or death, whichever occurred first (average of 10 study weeks)
PFS is defined as the interval between the date of randomization and the first documented sign of investigator-assessed (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) disease progression (PD) or death, whichever occurs first. The date of documented PD is the date of lesion evaluation in the case of radiological PD and the date of symptomatic cancer progression in the case of symptomatic progression (radiological confirmation is required). PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. If the participant received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS was to be censored at the last adequate assessment (LAA) prior to the initiation of therapy. Otherwise, if the participant did not have a documented date of progression or death, PFS was to be censored at the date of the LAA.
14 secondary outcomes
Overall Survival
Time frame: From randomization until disease progression or death (up to Study Week 78)
Number of Participants (Par.) With the Indicated Best Overall Response
Time frame: From randomization until the time of the first documented evidence of a confirmed complete response (CR) or partial response (PR) (average of 10 weeks)
Number of Participants With Any Non-serious On-therapy Adverse Event (AE: Occurring in >=5% Participants in Any Treatment Arm) and Serious Adverse Event (SAE)
Time frame: From the time the first dose of study treatment was administered until 28 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (up to Study Week 55)
Time on Study Treatment (Pazopanib), as a Measure of Extent of Exposure
Time frame: From the first day to the last day of treatment (average of 8 weeks)
Mean Daily Dose, as a Measure of Extent of Exposure
Time frame: From the first day to the last day of treatment (average of 8 weeks)
Mean Number of Pemetrexed Dosing Cycles, as a Measure of Extent of Exposure
Time frame: From the time the first dose of study treatment was administered until discontinuation of the study or death (average of 16 weeks)
Average Dose of Pemetrexed for All Cycles, as a Measure of Extent of Exposure
Time frame: From the time the first dose of study treatment was administered until discontinuation of the study or death (average of 16 weeks)
Number of Participants With Any AE (Serious or Non-serious) Leading to Withdrawal From Study Treatment
Time frame: From the time the first dose of study treatment was administered until withdrawal from study treatment (up to Study Week 55)
Number of Participants With Any On-therapy AE (Serious or Non-serious) Leading to Dose Reductions (DRs) or Interruptions/Delays in the Study
Time frame: From the time the first dose of study treatment was administered until discontinuation of treatment (up to Study Week 55)
Number of Participants With the Indicated Worst-case Change From Baseline in Blood Pressure
Time frame: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)
Number of Participants With a Increase From Baseline in Bazett's QTc at the Indicated Time Points
Time frame: Baseline; Week 6; Week 15; every 9 weeks in the first 6 months; every 12 weeks in the next 6 months; and, after 1 year, every 6 months (up to Study Week 55)
Number of Participants With a Change From Baseline Grade to Grade 3 and 4 for the Indicated Clinical Laboratory Parameters
Time frame: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)
Number of Participants With the Indicated Grade Changes From Baseline Grade in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk. Phos.), and Total Bilirubin (TB)
Time frame: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)
Number of Participants With the Indicated Changes From Baseline Value in Lactate Dehydrogenase (LDH)
Time frame: From the time of the first dose of study treatment until 28 days following discontinuation of study treatment (up to Study Week 55)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
25 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 pazopanib and pemetrexed in people with Lung Cancer, Small Cell, run by GlaxoSmithKline at 25 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 11 inclusion and 32 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 27 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 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 29 Apr 2013). 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: From randomization until the first documented sign of investigator-assessed disease progression or death, whichever occurred first (average of 10 study weeks)). 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 27 Oct 2014; AzTrials last refreshed its copy on 2 Nov 2026.