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Efficacy and Safety of MYL-1402O Compared With Avastin in the First-line Treatment of Patients with Stage IV Non-Squamous Non-Small Cell Lung Cancer
Last Updated on: 2017-01-27 13:29:53
Registry ID: PHRR170127-001478
Secondary Identification Number: 2016-CT0377; 2016-CT0377


Scientific Title

Multicenter, Double-Blind, Randomized, Parallel-Group Study to Assess the Efficacy and Safety of MYL-1402O Compared With Avastin in the First-line Treatment of Patients with Stage IV Non-Squamous Non-Small Cell Lung Cancer

Project Description

The study is a multicenter, randomized, double-blind, 2-arm, parallel-group, equivalence study to evaluate patients with Stage IV nsNSCLC when treated in first-line with bevacizumab (either MYL-1402O [test product] or Avastin [reference product]) in combination with CP and subsequently, with monotherapy of bevacizumab (either MYL-1402O or Avastin). The study is comprised of 5 periods: Screening/Baseline Period, Period 1, Period 2, Extended Treatment Period, and Survival Period. For Period 1 and Period 2, the length of the period is defined by the tumor assessments interval (every 6 weeks or every 12 weeks, respectively).

NUHRA Details
NUHRA Regime NUHRA Classification NUHRA Priority
2010 - 2016 Health Technology Development Drug Discovery and Development
Project Duration
Start Date Duration in Months Target Completion Date Actual Completion Date
2017-06-01 18 2018-12-01 0000-00-00
Project Status

Pending

Reason for Project Pending/Suspension/Termination

Awaiting for Sites EC Approval

Implementing Agency (Primary Sponsor)

Name of Institution Classification Region LTO #
MYLAN GmbH Private Business Switzerland N/A

Cooperating Agency (Secondary Sponsor)

Name of Institution Classification Region LTO #
PPD Pharmaceutical Development Philippines Corporation Private Business NCR CDRR-NCR-CRO-22

Funding Agency (Sources of Monetary or Material Support)

1. MYLAN GmbH

Contact for Public Queries

Name: Email Address: Phone Number: Postal Address:
Dr. Eduardo Penella, MD eduardo.penella@mylan.com N/A 1000 Mylan Boulevard Canonsburg,PA 15317 USA

Contact for Scientific Queries

Name: Email Address: Phone Number: Postal Address:
Dr. Eduardo Penella, MD eduardo.penella@mylan.com N/A 1000 Mylan Boulevard Canonsburg,PA 15317 USA

Investigating Team

Name Expertise Affiliation
Ma. Luisa Abesamis-Tiambeng, MD Oncologist Cardinal Santos Medical Center
Jorge Ignacio, MD Oncologist Philippine General Hospital
Maximino De Guzman Bello III, MD Oncologist St. Luke's Medical Center - Quezon City

Health Condition(s) or Problem(s) Studied

Patients with Stage IV Non-Squamous Non-Small Cell Lung Cancer

Primary Outcomes

 

Primary objective


Compare the overall response rate (ORR) of MYL-1402O with that of
Avastin, in combination with CP chemotherapy during the first18 weeks of first-line treatment in patients with Stage IV nsNSCLC

 

 

Key Secondary Outcomes

Secondary objectives

·Assess the safety profile of MYL-1402O as compared with that

of Avastin when administered in combination with CP as first-line treatment for Stage IV nsNSCLC and when administered alone in the maintenance setting

·Assess other efficacy parameters: Disease Control Rate (DCR),

Duration of Response (DR), Time To Progression (TP), Progression-Free survival (PFS), and Overall Survival (OS) of MYL-1402O as compared to Avastin when administered in combination with CP as first-line treatment for Stage IV nsNSCLC

Assess the potential immunogenicity at Week 18 and 42 of treatment of MYL-1402O as compared with that of Avastin Compare the pharmacokinetic (PK) profile of MYL-1402O and Avastin using a population PK (PopPK) approach

Date of First Enrollment

2017-06-01

Recruitment Status

Pending

Countries of Recruitment

Philippines

Research Classification

Clinical Trial

Project Location & Institutional Ethics Review Board Which Approved the Study

Project Location Institutional Ethics Review Board
Cardinal Santos Medical Center Cardinal Santos Medical Center Ethics Review Committee
Philippine General Hospital Philippine General Hospital Ethics Review Board
St. Luke's Medical Center - Quezon City St. Luke's Medical Center Institutional Ethics Review Committee

FDA Document Tracking Number

20160930153644

FDA / ERC Approval Date

2017-01-09

Amendment Approval Dates/Reasons

None

Key Inclusion and Exclusion Criteria (CT)

Inclusion Criteria

 

A patient is eligible for inclusion in the study if he or she meets all of

the following criteria:

1. Has demonstrated the ability to understand verbal and/or written instructions, to provide written informed consent, and is capable and agreeable to comply with protocol requirements.

2. Male or female at least 18 years of age at the time of signing an informed consent form (ICF).

3. Has a documented imaging diagnosis of Stage IV unresectable,

recurrent or metastatic nsNSCLC.

4. Has documented histologic or cytologic diagnosis of advanced nsNSCLC with negative or unknown sensitizing epidermal growth factor receptor (EGFR) mutation, and negative or unknown echinoderm microtubule-associated protein-like 4-anaplastic

lymphoma kinase (EML4-ALK) rearrangement.

5. Has measurable disease with at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1; Section 12.1 [Appendix A]). All target (up to 5 lesions) and nontarget lesions (other measurable not included in

target, nonmeasurable, nonevaluable, or evaluable lesions) should be included in the assessment or evaluation of disease response as defined by RECIST 1.1 (Eisenhauer et al 2009).

6. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.

7. Has at least 6 months of expected survival.

8. Has not received any prior systemic therapy for first-line treatment of advanced lung cancer, except adjuvant chemotherapy, and remained disease-free for at least 12 months from time of surgery, and at least 6 months from last dose of chemotherapy.

9. May have had prior radiation therapy provided <25% of bone marrow is involved (Section 12.3 [Appendix C]), except for previous mediastinal irradiation that is not allowed.

a. Prior radiation therapy must have been completed at least 2 weeks prior to Day 0 of Cycle 1

b. Patient must have recovered from acute toxicities associated with radiation therapy. Radiation-related toxicities must have resolved to Grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE; version 4.03) grade prior to Day 0 of Cycle 1.

10. May have brain metastasis provided the metastasis has been treated and is considered stable at the time of signing the informed consent form. Treated, stable brain metastasis is defined as:

a. Metastasis having no evidence of progressive disease (PD) or hemorrhage after treatment.

b. No ongoing requirement for dexamethasone, as ascertained byclinical examination and post-treatment brain imaging (computed tomography [CT] scan or magnetic resonance imaging [MRI]) at baseline.

c. Anticonvulsants are allowed, provided the dose regimen has been unchanged (stable) for at least 2 weeks prior to patient signing informed consent.

d. Treatment for brain metastasis may include whole brain radiotherapy, radiosurgery (Gamma Knife®, linear particle accelerator, or equivalent), or a combination thereof, as deemed appropriate by the treating physician. All brain metastasis treatments must be completed at least 14 days prior to Day 0 of Cycle 1.

11. Has adequate organ functions based on the following:

a. Bone marrow reserve:

i. White blood cell count ≥3 × 103/µL;

ii. Absolute neutrophil count (segmented and bands)≥1.5 × 103/µL;

iii. Platelet count ≥100 × 103/µL;

iv. Hemoglobin ≥9.0 g/dL with at least 2 weeks without transfusions before Day 0 of Cycle 1.

b. Hepatic:

i. Total bilirubin ≤1.5 × upper limit of normal (ULN); except if elevation is due to Gilbert’s Syndrome with transitory elevations of indirect bilirubin.

ii. Alkaline phosphatase, alanine transaminase, and/or aspartate transaminase ≤3 × ULN. Significant levels of alanine transaminase or aspartate transaminase should be

further assessed for viral hepatitis. (Note: Isolated alkaline phosphatase elevation beyond 3 × ULN due to bone metastasis is allowed).

c. Renal:

i. Calculated creatinine clearance ≥45 mL/min based on the original, weight-based Cockcroft and Gault formula (Cockcroft and Gault 1976; Section 12.4 [Appendix D])

ii. Urine protein to creatinine ratio ≤1. A patient with urine protein to creatinine ratio > 1 may be enrolled if ≤2g of protein in 24-hour urine collection.

12. If capable of reproduction, patients and their partners must use contraceptive methods during the full duration of the study and for6 months after discontinuation of study.

A patient who is capable of reproduction must be willing to practice birth control by using 2 different highly effective double barrier methods of contraception, or abstinence from sexual intercourse for the duration of the study. In particular a female patient of childbearing potential must use amethod that results in less than 1% failure rate per year when useconsistently and correctly such as implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence, or

vasectomized partner.
A male patient of reproductive potential (defined as a male that has not had a vasectomy) must use a condom with spermicide and their female partner to use another highly effective form of contraception.

 

 

Exclusion Criteria

 

A patient who meets any of the following criteria will be excluded from the study:

1. Is pregnant or breast-feeding.

2. Has documented histology/cytology confirming any of the following:

a. Squamous non-small cell lung cancer. (Note: In the event of mixed tumor histology/cytology or predominant cell type other than non-squamous, eligibility will be determined based on the predominant cell type, which must be non-squamous.)

b. A patient with any small cell type or large cell neuroendocrine histology.

3. Has a recent (within 6 months prior to Day 0 of Cycle 1) cardiac condition as defined by the New York Heart Association Class II, III, or IV (AHA 1994).

4. Has a recent (within 6 months prior to Day 0 of Cycle 1) history of a significant vascular event (such as aortic aneurysm requiring surgical repair or a recent peripheral arterial thrombosis) and/or history of significant and unstable vascular disease.

5. Has a history of stroke or transient ischemic attack within 6 months prior to Day 0 of Cycle 1, or has a long-term history of more than one of the following vascular thromboembolic events:

a. Cerebrovascular accidents

b. Transient ischemic attacks

c. Myocardial infarctions

d. Venous thromboembolic reactions, including pulmonary embolism

6. Is receiving anticoagulant therapy that:

a. Is not considered ‘stable’, defined as dosage not maintained for at least 3 months prior to Day 0 of Cycle 1.

b. Is not within the targeted international normalized ratio at thetime of consent signing.

7. Has a current diagnosis, history, or risk of hemorrhage in the central nervous system (CNS), including the following:

a. Patient with CNS metastasis treated by neurosurgical resection or brain biopsy performed within 8 weeks prior to Day 0 of Cycle 1.

b. Patient should be off corticosteroids for at least 1 week (7 days) at the time of the post-treatment (for CNS metastasis) brain CT/MRI.

8. Has any prior history of hypertensive crisis and/or hypertensive encephalopathy, or has a current diagnosis or recent history of inadequately controlled hypertension (defined as systolic blood pressure >150 mm Hg and/or diastolic >100 mm Hg, while on antihypertensive medications).

Has a recent history of any of the following:

a. A major surgical procedure, open biopsy, open pleurodesis, or significant traumatic injury within 28 days prior to Day 0 of Cycle 1.

b. Documented history of conditions that may need surgery during the study or within 6 months of signing informed consent.

c. Has had either a core biopsy or other minor surgical procedure within 7 days prior to Day 0 of Cycle 1. (Note: Placement of a vascular access device, or a closed pleurodesis, thoracentesis, or mediastinoscopy are allowed).

10. Has a history of any of the following:

a. Hemoptysis (approximately >2.5 mL or a half teaspoon) within 3 months prior to Day 0 of Cycle 1.

b. A thoracic, central, mediastinal tumor location in contact with major vessels

c. A cavitated lung tumor.

11. Has a history of gastrointestinal fistula, perforation, or abscess.

12. Has a current diagnosis or history of a nonhealing wound, active ulcer, or untreated bone fracture.

13. Has prior history of another active malignancy within the last 5 years, other than adequately treated superficial basal cell, superficial/skin squamous cell carcinoma, or carcinomas in situ.

14. Has a known hypersensitivity to any component of carboplatin, paclitaxel, bevacizumab, Chinese hamster ovary cell products, or other recombinant human or humanized antibodies.

15. Has received treatment with any other investigational drug, within the last 30 days or at least 5 half-lives (if available), whichever is longer, should have elapsed prior to Day 0 of Cycle 1.

16. Has previously received treatment with the following:

a. Paclitaxel.

b. Bevacizumab (Note: Prior intravitreal administration of bevacizumab does not preclude study participation).

c. Anthracycline. (Note: May be allowed on a case by case basis after consulting with the medical monitor to rule out an increased risk of cardiac failure).

17. Has documented or known current alcohol/drug abuse that precludes his/her ability to adhere to the protocol.

18. Has any of the following concomitant treatments or conditions:

a. Concomitant vaccination that contains an attenuated virus, for instance Yellow Fever vaccine.

b. Has a known history of active or latent tuberculosis.

c. Has a concomitant systemic disorder (e.g., active infection including known human immunodeficiency virus, viral hepatitis B or C) that, in the opinion of the principal

investigator (PI; or designee), would compromise the patient's safety (for instance potential drug interactions, or ability to adhere to the protocol).

d. Has any other concomitant condition that precludes the participation in the study through increased risk to the patient and/or potential to impact the PI’s (or designee’s) ability to administer this protocol.

Study Type

Interventional

Intervention Name

MYL-1402O (test product)

Intervention Description

Mylan GmbH will provide adequate supplies of interventional therapies (MYL-1402O, Avastin, carboplatin, and paclitaxel). Chemotherapy pre-medications and any other medications will be procured locally by the site. Sites will also provide the infusion supplies from their stock. For this protocol, carboplatin and paclitaxel are considered non-investigational.

 

MYL-1402O (test product) and Avastin (reference product) will be packaged, labelled and supplied centrally to all sites from the Mylan-approved packaging vendor. The CP chemotherapy will be administered sequentially after IMP. This will also be packaged, labelled, and supplied centrally to all sites from the Mylan approved packaging vendor.

MYL-1402O and Avastin vials are not blinded. Each vial will be labelled with a blinded label as per local language and regulatory requirement. Each individual vial will then be placed into a labelled carton. The carton will have a blinded label applied to it. Once the vial is placed into the carton and tamper sealed, it is then blinded.

Method of Allocation

Randomized

Masking / Blinding

Double Blind

Masking Details

None

Assignment

Parallel

Purpose

The primary objective of this study is to compare the ORR of MYL-1402O with that of

Avastin, in combination with CP chemotherapy during the first 18 weeks of first-line

treatment in patients diagnosed with Stage IV nsNSCLC.

Phase

Phase II/III

Target Sample Size (Philippines)

100

Actual Sample Size (Philippines)

0

Reason for the difference between target & actual sample sizes

N/A, not yet recruiting

Date of first enrollment

2017-06-01

Research Utilization

None