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.

• Register: EUCTR
• Last refreshed on: 26 March 2018
• Main ID: EUCTR2014-003878-16-GR
• Date of registration: 13/08/2015
• Prospective Registration: No
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017
• Public title: 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.
• Scientific title: A Phase 3 randomized, double-blind study of PF-06439535 plus Paclitaxel-Carboplatin and Bevacizumab plus Paclitaxel-Carboplatin for the first-line treatment of patients with advanced non-squamous non-small cell lung cancer.
• Date of first enrolment: 29/07/2015
• Target sample size: 798
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003878-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Brazil, Chile, Croatia, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, India, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, Peru, Philippines, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Taiwan, Thailand, Turkey, Ukraine, United States

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
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
Exclusion criteria:
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

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Advanced non-squamous non-small cell lung cancer.
MedDRA version: 18.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Bevacizumab-Pfizer
Product Code: PF-06439535
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEVACIZUMAB
Current Sponsor code: PF-06439535
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Avastin 100mg/4ml & 400mg/16ml concentrate for solution for infusion
Product Name: Avastin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Primary end point(s): Objective Response Rate (ORR), evaluating the best response achieved by Week 19 and subsequently confirmed by 6 weeks thereafter, in accordance with Response Evaluations Criteria in Solid Tumors (RECIST) version 1.1.

Secondary Objective: To evaluate the safety of bevacizumab-Pfizer plus paclitaxel and carboplatin and
bevacizumab-EU plus paclitaxel and carboplatin;

To evaluate secondary measures of tumor control;

To evaluate the population pharmacokinetics (PK) of bevacizumab-Pfizer and
bevacizumab-EU;

To evaluate the immunogenicity of bevacizumab-Pfizer and bevacizumab-EU.

Timepoint(s) of evaluation of this end point: At Week 19 and subsequently confirmed by 6 weeks thereafter.

Main Objective: The primary objective of this study is to compare the confirmed objective response rate (ORR) by Week 19 following treatment with bevacizumab-Pfizer in combination with paclitaxel and carboplatin to bevacizumab-EU plus paclitaxel and carboplatin in patients who have not received previous treatment for advanced non-squamous non-small cell lung cancer (NSCLC).

Secondary Outcome(s)

Secondary end point(s): • Safety characterized by type, incidence, severity, timing, seriousness, and relationship to study therapy of adverse events, including cardiotoxicity and infusion-related reactions, and laboratory abnormalities;

• Duration of response (DOR), 1 year progression-free survival (PFS) rate and 1-year survival rate;

• Peak and trough bevacizumab-Pfizer and bevacizumab-EU concentrations at selected cycles;

• Incidence of anti-drug (bevacizumab) antibodies (ADA), including neutralizing antibodies (NAb).

Timepoint(s) of evaluation of this end point: 1 Year

Secondary ID(s)

2014-003878-16-SK

B7391003

Source(s) of Monetary Support

Pfizer Inc. 235 East 42nd Street, New Yor, NY 10017