A study to test if PF-06439535 plus Paclitaxel-Carboplatin compared to Bevacizumab plus Paclitaxel-Carboplatin is an effective treatment in patients with advanced non-squamous non-small cell lung cancer.
- Conditions
- Advanced non-squamous non-small cell lung cancer.MedDRA version: 18.0Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-003878-16-GR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 798
Patient eligibility should be reviewed and documented by an appropriate member of the investigator’s study team before patients are included in the study.
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Male and female patients age =18 years of age, or = age of consent in the region.
2. Newly diagnosed Stage IIIB or IV non-small cell lung cancer (according to Revised International System for Staging Lung Cancer criteria of 2010) or recurrent non-small cell lung cancer (NSCLC) for which they had not received chemotherapy for
metastatic disease.
3. Histologically or cytologically confirmed diagnosis of predominately non-squamous NSCLC.
4. At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
5. For patients with recurrent disease, at least 6 months must have elapsed since completing adjuvant or neoadjuvant treatment.
6. Patients must have had a baseline scan (computed tomography [CT] or magnetic resonance imaging [MRI]) of the chest, abdomen, and other disease sites, as clinically indicated, to assess disease burden performed within 28 days prior to randomization.
7. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
8. Screening laboratory values within the following limits (where deviation of up to 10% is acceptable for any single value if in the investigator’s opinion the patient does not have an increased safety risk):
Bone Marrow Function
a. Absolute neutrophil count (ANC) =1.5 x 10x9 cells/L (1500/mm3);
b. Platelet count =100 x 10x9 cells/L (100,000/mm3);
c. Hemoglobin =9.0 g/dL (90 g/L);
Renal Function
d. Serum creatinine =1.5 x upper limit of normal (ULN);
e. Urine dipstick proteinuria <2+ (ie, either 0, trace, or 1+). If urine dipstick is >1+ then a 24 hour urine for protein must have demonstrated urinary excretion of =500 mg of protein per day;
Liver Function
f. Total bilirubin =1.5 x ULN (<3 ULN if Gilbert’s disease);
g. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =3 x ULN (=5 x ULN if liver metastases are present).
9. Recovery (to Grade 1 or baseline) from all clinically significant adverse effects of prior therapies (excluding alopecia).
10. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
11. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
12. Male and female subjects of childbearing potential and at risk for pregnancy must agree to use two highly effective methods of contraception throughout the study and for at least 6 months after the last dose of assigned treatment (bevacizumab-Pfizer or
bevacizumab-EU).
Female subjects who are not of childbearing potential (ie, meet at least 1 of the following criteria):
• Have undergone a documented hysterectomy and/or bilateral oophorectomy;
• Have medically confirmed ovarian failure; or
• Achieved postmenopausal status, defined as follows: cessation of regular menses
for at least 12 consecutive months with no alternative pathological or
physiological cause; and have a serum follicle stimulating hormone (FSH) level within the laboratory’s reference range for postmenopausal women.
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 s
1. Small cell lung cancer (SCLC) or combination SCLC and NSCLC. Squamous-cell tumors and mixed adenosquamous carcinomas of predominantly squamous nature.
2. Evidence of a tumor that compresses or invades major blood vessels or tumor cavitation.
3. Known sensitizing EGFR mutations (for example, deletion 19 or L858R) or EML4-ALK translocation positive mutations.
4. History of other cancer within 5 years prior to screening for this study, with the exception of adequately treated ductal carcinoma in situ of the breast, cervical carcinoma in situ, or basal or squamous cell skin cancer.
5. Prior systemic therapy for metastatic disease.
6. History of hemoptysis (>2.5 mL per event) in the last 3 months or severe bleeding. Evidence of current thrombotic or bleeding disorders. Systemic anticoagulation or chronic therapy with prescription non-steroidal anti-inflammatory drugs (NSAIDs), aspirin >325 mg, or other non-selective NSAIDs above the maximum allowed over
the counter (OTC) dose, and/or coagulation abnormalities (eg, INR >1.5 and aPTT greater than ULN within 1 week prior to randomization). [Some NSAIDs have effects on platelet function (see Prescribing Information for the specific NSAID). In the event that a patient’s NSAID therapy exceeds the maximum dose of OTC medication, the investigator should contact the Sponsor for approval of patient inclusion. Approval will be based on the type of NSAID therapy, the dose, and the patient’s other known risk factors.]
7. Medically uncontrolled hypertension or systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg.
8. Peripheral motor or sensory neuropathy with value of =2.
9. Major surgery, radiotherapy, or any investigational agents, within 4 weeks before the administration of the first dose of study treatment. Planned major surgery during the treatment period.
10. Any unhealed wound or bone fracture.
11. Infection requiring a course of systemic anti-infective agents within 3 weeks prior to randomization. Patients must be off of antibiotics for 7 days.
12. Comorbities that would increase the risk of toxicity as per the investigator’s discretion.
13. Concurrent administration of other anticancer therapies. Bisphosphonate or Rank-Ligand inhibitor therapy for pre-existing bone metastases or osteoporosis is allowed.
14. Known central nervous system (CNS) metastases, as evidenced by appropriate scans, clinical symptoms, cerebral edema, and/or progressive growth.
15. Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (CHF) New York Heart Association (NYHA) functional classification of =3, unstable angina, or myocardial infarction within 12 months before first dose of study treatment. Clinically significant cardiovascular disease, peripheral vascular disease, transient ischemic attack, cerebrovascular accident.
16. History of severe hypersensitivity reaction to any of the products to be administered during the study, including mammalian cell derived drug products, taxanes, bevacizumab, murine proteins, or excipients in their formulations.
17. Clinical contraindication to treatment with steroids preventing use as part of paclitaxel premedication.
18. Pregnant female patients; breastfeeding female patients; male patients with partners currently pregnant; male and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol from at least 19 days prior
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method