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GW786034 in Patients With Non Small Cell Lung Cancer 3rd Line

This study has been terminated.
(Study was terminated due to positive results seen in statistical analysis. Adequate patient enrollment was achieved.)
Sponsor:
Information provided by (Responsible Party):
Sachdev Thomas, Illinois CancerCare, P.C.
ClinicalTrials.gov Identifier:
NCT01049776
First received: January 12, 2010
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

Lung Cancer is the most common cause of cancer death in the United States with an estimated mortality in excess of 160,000, more than the combined mortality seen with prostate, breast, colorectal cancers(1). Most patients with Lung Cancer have Non-Small Cell Lung Cancers( NSCLC) and only 25-30% of patients with NSCLC (Non Small Cell Lung Cancer) have resectable disease( Stage I or II) at the time of diagnosis.

The vast majority of patients with advanced NSCLC (Non Small Cell Lung Cancer) are not curable and overall five year survival is 11%-14%1.

Chemotherapy is beneficial for patients with locally advanced and metastatic disease. Numerous phase III studies have determined the superiority of systemic chemotherapy over best supportive care. Platinum based chemotherapy has been widely accepted as the standard of care for the initial treatment of advanced NSCLC.

However first line chemotherapy is modest at best. A randomized trial comparing four of the most commonly used chemotherapy regimens in the United States not only failed to show a clearly superior arm but also confirmed the dismal prognosis of these patients. The response rate for all 1207 patients was 18.6% with a median survival of eight months and one year survival of 33.5 % and a two year survival of 12%5. Clearly a different paradigm is needed for the treatment of this disease.


Condition Intervention Phase
Non Small Cell Lung Cancer
Drug: Pazopanib (GW786034)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of GW786034 in Patients With Non Small Cell Lung Cancer Who Have Failed at Least Two Prior Chemotherapy Regimens. An Institutional Pilot Study

Resource links provided by NLM:


Further study details as provided by Illinois CancerCare, P.C.:

Primary Outcome Measures:
  • Proportion of Non Small Cell Lung Cancer Participants With Disease Control (Complete Response+Partial Response+Stable Disease) Based on RECIST 1.0 Measured by CT or MRI [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions: Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesion, taking as reference the baseline sum of the longest diameter: Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease, taking as reference the smallest sum Longest Diameter since the treatment started


Secondary Outcome Measures:
  • To Describe the Clinical Toxicity Profile of Pazopanib in This Particular Patient Population [ Time Frame: after the first 6 patients and quarterly ] [ Designated as safety issue: Yes ]

Enrollment: 32
Study Start Date: January 2010
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pazapanib (GW786034) Drug: Pazopanib (GW786034)
Pazopanib 800 mg daily x 12 weeks, (Cycle = 21 days) up to 24 months
Other Name: Pazopanib monohydrochloride salt GW786034

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Required Characteristics 3.1. Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up. Procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.

Note: It is not necessary that informed consent be obtained within the protocol-specified screening window.

3.11 ≥18 years of age.

3.12 ≥2 prior systemic therapies for Non Small Cell Lung Cancer.

3.13 Histologic or cytologic diagnosis of stage IV Non Small Cell Lung cancer

. 3.14 Measurable disease. For patients having only lesions measuring ≥1 cm to ≤2 cm per RECIST criteria must use spiral CT imaging for both pre- and post-treatment tumor assessments.

3.15 Laboratory values obtained ≤14 days prior to registration: Hematologic Absolute neutrophil count (ANC) 1.5 X 109/L Hemoglobin1 9 g/dL (5.6 mmol/L) Platelets 100 X 109/L Prothrombin time (PT) or international normalized ratio (INR) 1.2 X upper limit of normal (ULN) Partial thromboplastin time (PTT) 1.2 X ULN Hepatic2 Total bilirubin 1.5 X ULN AST and ALT 2.5 X ULN Renal Serum creatinine 1.5 mg/dL (133 µmol/L)

Or, if greater than 1.5 mg/dL:

Calculated creatinine clearance 50 mL/min

Urine Protein to Creatinine Ratio (UPC)3 < 1

  1. Subjects may not have had a transfusion within 7 days of screening assessment.
  2. Concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN are not permitted
  3. If UPC >/= 1, then a 24-hour urine protein must be assessed. Subjects must have a 24-hour urine protein value <1g to be eligible.

    3.16 ECOG Performance Score 0, or 1.

    3.17 Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.

    A female is eligible to enter and participate in this study if she is of: Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had:

    • A hysterectomy
    • A bilateral oophorectomy (ovariectomy)
    • A bilateral tubal ligation
    • Is post-menopausal

    Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for ≥ 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >40 mIU/mL and an estradiol value < 40pg/mL (<140 pmol/L).

    Subjects using HRT must have experienced total cessation of menses for >= 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT

    Childbearing potential, including any female who has had a negative serum pregnancy test within 1 week prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:

    • An intrauterine device with a documented failure rate of less than 1% per year.
    • Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.
    • Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product.
    • Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide).
    • Oral contraceptives
    • Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug

    3.18 Ability and willingness to provide informed consent.

    3.19 Life expectancy ≥12 weeks.

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    Exclusion Criteria:

    3.21 Any of the following as this regimen may be harmful to a developing fetus or nursing child.

    • Pregnant women

    • Nursing women
    • Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception.

    3.22 Any abnormal serum calcium, magnesium, and potassium levels

    3.23 Clinically significant hemoptysis, cerebral hemorrhage, or gastrointestinal hemorrhage in the past 6 months

    3.24 Any patient currently on an antiarrhythmics or other medications that are know to prolong the QT interval.

    3.25 Uncontrolled infection.

    3.26 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. 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

    3.27 Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures, affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain pazopanib tablets.

    • Malabsorption syndrome
    • Major resection of the stomach or small bowel. 3.28 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
    • History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.

    3.29 Known endobronchial lesions and or lesions infiltrating major pulmonary vessels.

    3.30 Cavitary lesions deemed to be at increased risk of bleeding.

    3.31 Any other severe underlying diseases that are, in the judgment of the investigator, inappropriate for entry into this study.

    3.32 Second primary malignancy except for carcinoma in situ of the cervix or nonmelanomatous skin cancer, unless that prior malignancy was diagnosed and definitively treated ≥5 years previously with no subsequent evidence of recurrence. Patients with a history of low-grade (Gleason score ≤6) localized prostate cancer will be eligible even if diagnosed <5 years prior to registration.

    3.33 Any ancillary therapy considered investigational (utilized for a non-FDA approved indication and in the context of a research investigation) ≤4 weeks prior to registration.

    3.34 Other concurrent chemotherapy, immunotherapy, radiotherapy.

    3.35a. History of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib or other agents used in the study.

    b. Medications that act through the CYP450 system. Some medications that act through the cytochrome P450 system are specifically prohibited in patients receiving pazopanib. Certain other agents should be used with caution. (A list of medications that are specifically prohibited or that should be used with caution during this trial of pazopanib will be provided with the full study protocol as Appendix 1. A list of selected agents that could affect pazopanib will be listed in Appendix I. ) c. Any of the following concurrent severe and/or uncontrolled medical conditions:

    • Serious or non-healing wound, ulcer, or bone fracture

    • History of abdominal fistula, diverticulosis, gastrointestinal perforation, or intra-abdominal abscess ≤28 days prior to registration

    • Any history of cerebrovascular accident (CVA) ≤6 months prior to registration
    • 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)
    • History of venous thrombosis ≤12 weeks prior to registration.
    • Class III or IV heart failure as defined by the NYHA functional classification system .History of Class II heart failure and is asymptomatic on treatment may be considered eligible.
    • Poorly controlled diabetes.
    • Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.
    • QTc prolongation (defined as a QTc interval ) > 480 msecs using Bazett's formula) or other significant ECG abnormalities d. Symptomatic, untreated, or uncontrolled CNS metastases or seizure disorder. Patients with CNS metastases treated with whole brain radiation (WBRT)or gamma knife may be enrolled after completion of WBRT or gamma knife. Patients may begin chemotherapy as early as the next day after completion of WBRT or gamma knife.

      e. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.

      f. HIV-positive patients on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with pazopanib. In addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy

      g. Any of the following prior therapies:

    • Major surgery (i.e., laparotomy), open biopsy, or significant traumatic injury ≤4 weeks prior to registration. Minor surgery ≤4 weeks prior to registration. Insertion of a vascular access device is not considered major or minor surgery in this regard.
    • 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

    Patients with progressive disease inside of the radiation field are not eligible.

    3.36 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

    3.37 Evidence of active bleeding or bleeding diathesis.

    3.38 Hemoptysis within 6 weeks of first dose of study drug.

    3.39 Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.

    3.40 Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.

    3.41 Other Eligibility Criteria Considerations To assess any potential impact on subject eligibility with regard to safety, the investigator must refer to the following document(s) for detailed information regarding warnings, precautions, contraindications, adverse events, and other significant data pertaining to the investigational product(s) being used in this study: Clinical Investigator's Brochure for pazopanib.[Investigator Brochure]

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  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01049776

Locations
United States, Illinois
Illinois CancerCare, P.C.
Bloomington, Illinois, United States, 61701
Illinois CancerCare, P.C.
Canton, Illinois, United States, 61520
Illinois CancerCare, P.C.
Carthage, Illinois, United States, 62321
Illinois CancerCare, P.C.
Eureka, Illinois, United States, 61530
Illinois CancerCare, P.C.
Galesburg, Illinois, United States, 61401
Illinois CancerCare, P.C.
Macomb, Illinois, United States, 61455
Illinois CancerCare, P.C.
Monmouth, Illinois, United States, 61462
Illinois CancerCare, P.C.
Normal, Illinois, United States, 61761
Illinois CancerCare, P.C.
Ottawa, Illinois, United States, 61350
Illinois CancerCare, P.C.
Pekin, Illinois, United States, 61554
Illinois CancerCare, P.C.
Peoria, Illinois, United States, 61615
Illinois CancerCare, P.C.
Peru, Illinois, United States, 61354
Illinois CancerCare, P.C.
Princeton, Illinois, United States, 61356
Sponsors and Collaborators
Illinois CancerCare, P.C.
Investigators
Principal Investigator: Sachdev P. Thomas, M.D. Illinois CancerCare, P.C.
  More Information

No publications provided

Responsible Party: Sachdev Thomas, Principal Investigator, Illinois CancerCare, P.C.
ClinicalTrials.gov Identifier: NCT01049776     History of Changes
Other Study ID Numbers: ILCC #2 IllinoisCancerCare #2
Study First Received: January 12, 2010
Results First Received: August 11, 2014
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Illinois CancerCare, P.C.:
Lung Cancer Non Small Cell

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms

ClinicalTrials.gov processed this record on November 25, 2014