A Phase II, randomised, multicentre study to evaluate the efficacy and safety of pazopanib in combination with pemetrexed versus cisplatin plus pemetrexed, as first-line therapy in subjects with stage IIIB/IV non-small cell lung cancer

• Conditions: Histologically- or cytologically-confirmed diagnosis of non-predominantly squamous cell Stage IIIBwet (with confirmed malignant pleural effusion) or Stage IV NSCLC; MedDRA version: 9.1Level: LLTClassification code 10029521Term: Non-small cell lung cancer stage IIIB; MedDRA version: 9.1Level: LLTClassification code 10029522Term: Non-small cell lung cancer stage IV

• Registration Number: EUCTR2008-002144-42-DK
• Lead Sponsor: GlaxoSmithKline R&D Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-04-21
• Last Update Posted: 24 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Specific information regarding warnings, precautions, contraindications, AEs, and other pertinent information on the IP that may impact subject eligibility is provided in the IB for pazopanib. For pemetrexed and cisplatin, please refer to the approved product labels.
Subjects eligible for enrollment in the study must meet all of the following criteria:
1.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 assessments. 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 used for screening or baseline purposes provided these procedures were conducted as specified in the protocol.
2.Age ?18 years old (or legal age of consent if greater than 18 years)
3.Histologically- or cytologically-confirmed diagnosis of predominantly non-squamous cell Stage IIIBwet (with confirmed malignant pleural effusion) or Stage IV NSCLC.
4.ECOG performance status of 0 or 1 (Appendix 3).
5.Life expectancy of at least 12 weeks.
6.Measurable disease as defined by RECIST criteria (Section 6.2.3) [Therasse, 2000]
7.No prior systemic first-line therapy for Stage IIIBwet/IV NSCLC either by chemotherapy or any other systemic treatment. Prior surgery and/or localised irradiation for NSCLC are permitted as long as it was a minimum of 4 weeks before entering the study; however, single-dose palliative radiation of bone metastases for pain control may be allowed during the 4-week screening period (see Section 5.11.3). Subjects with recurrence after previous NSCLC that has been treated with surgery, adjuvant, and/or neo-adjuvant chemotherapy, or a radio-chemotherapy regimen with curative intent are eligible, provided 1 year has passed since this treatment ended.
8.Able to swallow and retain oral medication.
9.Adequate organ system function as defined in Table 3 of the protocol.
10.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
•Or who 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 <40 pg/mL (<140 pmol/L). For most forms of HRT, at least 2 to 4 weeks must elapse between the cessation of HRT and determination of menopausal status; length of this interval depends on the type and dosage of HRT. If a female subject is determined not to be post-menopausal, she must use adequate contraception, as defined immediately below.
Childbearing potential, including any female who has had a negative serum pregnancy test within one 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 follows:
•An intrauterine device with a documented failure rate of less than 1% per year.
•Vasectomised partner who is sterile prior to the female subject’s entry and is the sole s

Exclusion Criteria

•Active malignancy or any malignancy in the 3 years prior to first dose of study drug other than NSCLC. Subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
•History or clinical evidence of 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 medication for 1 week prior to first dose of study drug. Screening with CNS imaging (computerised 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 including, but not limited to:
oMalabsorption syndrome .
oMajor resection of the stomach or small bowel that could affect the absorption of study drug.
oActive peptic ulcer disease.
oKnown intraluminal metastatic lesion/s with risk of bleeding.
oInflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation.
oHistory of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
•Presence of uncontrolled infection.
•Prolongation of heart-rate corrected QT interval (QTc) >480 msecs (using Bazett’s formula).
•History of at least one of the following cardiovascular conditions within the past 6 months:
oCardiac angioplasty or stenting.
oMyocardial infarction.
oUnstable angina.
oSymptomatic peripheral vascular disease.
oClass III or IV congestive heart failure, as defined by the New York Heart Association (NYHA; Appendix 4).
•Poorly controlled hypertension [defined as systolic blood pressure (SBP) of =140 mmHg or diastolic blood pressure (DBP) of =90 mmHg].
oNote: 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 (See Section 6.3.3 for details on BP control and re-assessment prior to study enrollment).
•History of cerebrovascular accident, including transient ischemic attack (TIA), PE, or untreated DVT within the past 6 months.
oNote: 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.
•Evidence of active bleeding or bleeding diathesis.
•Recent haemoptysis (½ teaspoon of red blood within 8 weeks before first dose of study drug).
•Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary haemorrhage, (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 with study procedures.
•Use of any prohibited medication within the timeframes listed in Section 5.11.
•Prior use of an investigational

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified