A Phase 2 Efficacy And Safety Study Of Su011248 In Patients With Non-Small Cell Lung Cancer And Brain Metastases

• Conditions: on-Small cell lung cancer and brain metastases; MedDRA version: 14.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2006-004451-38-ES
• Lead Sponsor: Pfizer, S.L.U.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-29
• Last Update Posted: 18 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Histologically or cytologically confirmed NSCLC
2. Radiologically proven brain metastases secondary to histologically or cytologically confirmed NSCLC. Prior resection of brain metastases is allowed provided at least 1 metastatic brain lesion can be followed by postoperative MRI.
3. Previous whole brain radiation therapy ?2 weeks prior to study entry.
4. None, 1, or 2 prior systemic therapies for the treatment of dvanced/metastatic NSCLC.
5. Patients who received prior systemic therapy for the treatment of NSCLC must have evidence of disease progression.
6. Completion of all prior chemotherapy, immunotherapy, and radiotherapy ?4 weeks prior to study entry, and resolution of all acute toxic effects of any prior systemic anticancer therapy, radiotherapy, or surgical procedure to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade ?1. Note: WBRT may have occurred ?2 weeks prior to study entry.
7. For systemic disease, evidence of unidimensionally measurable disease. Measurable brain disease is not required.
8. Male or female, 18 years of age or older.
9. ECOG performance status 0 or 1.
10. Adequate organ function as defined by the following criteria
*Serum aspartate aminotransferase (AST; serum glutamate-oxalate transferase
[SGOT]) and serum alanine aminotransferase (ALT; serum glutamate-pyruvate
transferase) [SGPT] ?2.5 x upper limit of normal (ULN)
*Total serum bilirubin ?1.5 mg/dL
*Prothrombin time (PT) ?1.5 x ULN
*Absolute neutrophil count (ANC) ?1500/mL
*Platelets ?100,000/mL
*Hemoglobin ?9.0 g/dL
*Serum creatinine ?1.5 x ULN
*Sodium ?120 mEq/L
11. Evidence of a personally signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
12. Subjects who are willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 9
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion Criteria

1. Brainstem lesions, spinal cord compression, carcinomatous meningitis, or
leptomenengeal disease
2. Brain metastases >4 cm in any linear direction
3. Candidate for definitive therapy for brain metastases (e.g. Gamma Knife, surgery).
4. Evidence of tonsillar or tentorial herniation
5. Intracranial or intratumoral hemorrhage (except those with punctuate asymptomatic intratumoral bleeds).
6. Uncontrolled seizure activity
7. Treatment with potent CYP3A4 enzyme inducers or inhibitors within the past 2 weeks. Note 1: Patients on steroids must be dose reduced to the lowest possible dose if steroids cannot be completely discontinued.
Note 2: Steroid dose must be stable (or decreasing) for at least 2 weeks at the time of study entry.Note 3: Patients taking anticonvulsants that affect CYP3A4 enzyme activity (e.g.phenytoin, carbamazepine) must switch to an anticonvulsant that is not a potent enzyme inducer, e.g. Keppra® (levetiracetam).
8. Current treatment with therapeutic doses of coumarin-derivative anticoagulants such as warfarin (however low dose up to 2 mg daily for deep vein thrombosis prophylaxis is permitted) or anti-vitamin K agents. If currently receiving prophylaxis, PT or INR must be <1.5 times the ULN.
9. Major surgery or radiation therapy <4 weeks of starting the study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated. Note 1: WBRT must have occurred ? 2 weeks prior to study entry. Note 2: Resection of brain metastases is allowed provided at least 1 metastatic lesion is available for follow-up.
10. NCI CTCAE Grade 3 hemorrhage <4 weeks of starting study treatment.
11. Evidence of hemoptysis <4 weeks of starting study treatment. Patients with blood-tinged or blood-streaked sputum will be permitted on study if the hemoptysis amounts to <5 mL of blood per episode and <10 mL of blood per 24-hour period in the best estimate of the investigator.
12. Uncontrolled hypertension defined as blood pressure >150/100 mm Hg that cannot be controlled with standard antihypertensive agents.
13. Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma that has been adequately treated with no evidence of recurrent disease for 12 months.
14. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolism.
15. Ongoing cardiac dysrhythmias of NCI CTCAE grade ?2, atrial fibrillation of any grade, or prolongation of the QTc interval to >450 msec for males or >470 msec for females.
16. Known human immunodeficiency virus (HIV) infection.
17. Current treatment on another therapeutic clinical trial.
18. Pregnancy or breastfeeding. Female patients must be surgically sterile or be
postmenopausal, or must agree to use effective contraception during the period of therapy. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to study treatment.
19. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the inves

Study & Design

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