| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Newly diagnosed or recurrent Stage IIIB/IV Non Squamous (ns) Non-Small Cell Lung Cancer (NSCLC). |
|
| E.1.1.1 | Medical condition in easily understood language |
| Newly diagnosed or recurrent Stage IIIB/IV Non Squamous (ns) Non-Small Cell Lung Cancer (NSCLC). |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025054 |
| E.1.2 | Term | Lung cancer non-small cell stage IIIB |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025055 |
| E.1.2 | Term | Lung cancer non-small cell stage IV |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10029521 |
| E.1.2 | Term | Non-small cell lung cancer stage IIIB |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10029522 |
| E.1.2 | Term | Non-small cell lung cancer stage IV |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To demonstrate the equivalence in efficacy by comparing Overall
Response Rate (ORR) of BP01 (Bevacizumab) with Avastin®-EU at
completion of the Induction Phase. |
|
| E.2.2 | Secondary objectives of the trial |
To assess the progression free survival (PFS) and overall survival
(OS) of BP01 (Bevacizumab) as compared to Avastin®-EU.
• To assess duration of response (DOR) and disease control rate
(DCR) of BP01 (Bevacizumab) as compared to Avastin®-EU.
• To assess the safety profile of BP01 (Bevacizumab) as compared
to Avastin®- EU.
• To assess immunogenicity of BP01 (Bevacizumab) as compared
to Avastin®-EU.
• To assess the population pharmacokinetics (Ctrough)of BP01 (Bevacizumab) as compared to Avastin®-EU |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Signed informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of subject’s awareness and willingness to comply with the study requirements.
2. Male and/ or female subjects aged ≥ 18 years to ≤ 70 years at the time of signing informed consent.
3. Subjects with histologic or cytologic diagnosis of nsNSCLC* with negative or unknown sensitizing epidermal growth factor receptor (EGFR) mutation and documented negative or unknown anaplastic lymphoma kinase (ALK) translocation.
* mixed cancer types should be classified according to the predominant cell type, if small cell elements are present, subjects must be excluded.
4. Subjects with newly diagnosed or recurrent Stage IIIB/ IV nsNSCLC.
5. Subjects must have at least 1 uni-dimensional measurable target lesion as per RECIST v1.1.
6. Subjects with Eastern Cooperative Oncology Group (ECOG) PS 0 or 1 at the time of screening and prior to first infusion.
7. Subjects who are newly diagnosed should not have received any prior chemotherapy or targeted therapy.
8. Subjects should not have received any immunotherapy or biological therapy for their disease.
9. Subjects received prior adjuvant chemotherapy for NSCLC is permitted if completed > 6 months prior to randomization.
10. Subjects received prior radiation therapy if completed > 4 weeks prior to randomization. Palliative radiotherapy to bone lesions is allowed if completed > 2 weeks prior to randomization.
11. Subjects must have a baseline scan of the chest, abdomen, and other disease sites, as clinically indicated, to assess disease burden performed within 21 days prior to randomization.
12. Subjects with life expectancy of at least 6 months.
13. Subjects must have adequate hepatic, renal and hematologic function defined as:
i. Hepatic Function:
Bilirubin ≤ 1.5 x upper limit of normal (ULN), alkaline phosphatase, alanine transaminase and aspartate transaminase ≤ 3 x ULN;
ii. Renal Function:
Serum creatinine ≤ 1.5 x ULN, calculated creatinine clearance (CrCl) > 30 mL/min (estimated by using Cockroft and Gault formula), urine protein to creatinine ratio ≤ 1**.
**Patients with UPCR > 1 may be enrolled if ≤ 2 g of protein (by either timed 24-hour or Overnight or untimed (“Spot”) urine sample collection); and
iii. Hematological Function:
White blood cell count ≥ 3000/μL, absolute neutrophil count (ANC) ≥ 1500/μL; platelets > 100000/μL, hemoglobin (Hb) ≥ 8.5 g/dL.
International normalised ratio (INR) ≤ 1.5 and partial thromboplastin time ≤ 1.5 × the upper limit of normal (ULN).
14. Subjects who has liver and/ or bone metastasis must have adequate organ function defined as:
i. Organ function: bilirubin ≤ 3 X upper limit of normal (ULN), alkaline phosphatase, alanine transaminase and aspartate transaminase ≤ 5 x ULN.
15. Female subjects of child-bearing potential must be non-lactating and have a negative serum pregnancy test at the time of screening.
16. Female subjects of childbearing potential agree to pregnancy prevention throughout the duration of study. Sexually active subjects must use contraception while on Bevacizumab from throughout the course of the study and should avoid mothering a child during course of the study and at least 3 months following last dose of IP.
17. Female subjects must agree to use of an effective method of contraception during study as mentioned below:
i. Barrier methods (condom or diaphragm with spermicide)
ii. Intrauterine device
iii. Hormone contraceptives (such as oral [pill], injection, skin patch, implant, cervical ring)
18. Male subject must agree to use acceptable methods of contraceptive throughout the course of the study and should avoid fathering a child during course of the study and at least 3 months following last dose of IP. |
|
| E.4 | Principal exclusion criteria |
1. Inability to comply with protocol procedures.
2. Subjects in another clinical trial or treatment with another investigational agent within 4 weeks of randomization, or five half-lives of investigational agent – if longer than 4 weeks.
3. Subjects with known hypersensitivity to the active ingredients or any of the excipients or Chinese Hamster Ovary (CHO) cell products, or other recombinant human or humanized antibodies and combination chemotherapy.
4. Subjects who are having Central Nervous System (CNS) disease including brain and spinal cord metastases.
5. Subjects are on corticosteroids therapy except as premedication (must be off corticosteroids for at least 4 weeks prior to randomization).
6. Subjects are on anticoagulation treatment for thromboembolism.
7. Subjects were previously treated with vascular endothelial growth factor receptor (VEGFR) directed therapy.
8. Subjects have predominantly squamous cell histology NSCLC and Small Cell Lung Cancer (SCLC).
9. Subjects have concomitant systemic disorder (Hepatitis B, Hepatitis C, or human immunodeficiency virus).
10. Female subjects who are pregnant or breastfeeding.
11. Subjects with prior major surgery, open biopsy, open pleurodesis, or significant traumatic injury within 4 weeks prior to randomization or have an anticipated need for major surgery during study.
12. Subjects having core biopsy, other minor surgical procedure, excluding placement of vascular access device, closed pleurodesis, thoracentesis, mediastinoscopy, taken within 1 week of randomization.
13. Subjects have history of stroke or transient ischemic attack within 6 months prior to randomization.
14. Subjects have prior history of hypertensive crisis or hypertensive encephalaopathy.
15. Subjects with previous malignancy within 5 years of randomization (other than superficial basal cell and superficial squamous cell cancer, or uterine, cervix, bladder, or prostate cancer).
16. Subjects with uncontrolled hypertension (defined as systolic blood pressure > 150 and/or diastolic > 100 mm Hg on antihypertensive medications).
17. Subjects with clinically significant cardiovascular disease: history of myocardial infarction, angina, or heart disease by NYHA Class II, III, or IV, within 6 months prior to randomization.
18. Subjects with a history of significant vascular event within 6 months prior to randomization (including, but not limited to myocardial infarction and stroke or transient ischemic attack).
19. Subjects with known bleeding diathesis or significant coagulopathy within 3 months prior to randomization.
20. Subjects with a history of abdominal fistula, gastro-intestinal perforation, intra abdominal abscess within 6 months of randomization.
21. Subjects with a non-healing wound, active ulcer, inflammatory bowel disease or untreated bone fracture.
22. Subjects with history of hemoptysis (approximately > 2.5 mL or a half teaspoon) within three months prior to randomization.
23. Subjects with tumour invading or compressing major blood vessels.
24. Subjects with history or presence of arterial/venous thromboembolic events.
25. Subjects with history or presence of Posterior Reversible Encephalopathy Syndrome (PRES).
26. Subjects with presence of Osteonecrosis of the jaw.
27. Subjects with known current alcohol/ drugs of abuse that precludes the ability of subject to adhere to the protocol.
28. Subjects with presence of any other concomitant condition, in the opinion of the investigator that precludes the subject’s participation in study considered high risk for treatment related complications. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall Response Rate (ORR) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Objective Response Rate (ORR) will be assessed up to 18 months. |
|
| E.5.2 | Secondary end point(s) |
•Progression-free survival (PFS)
•Overall survival (OS)
•Duration of response (DOR)
•Disease control rate (DCR)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Progression Free Survival (PFS): The time from randomization to the first documented disease progression (PD) or death, whichever occurs earlier.
• Overall Survival (OS): The time from randomization to death from any cause.
• Duration of Response (DOR): The time from start of the first documentation of
objective tumour response (CR or PR) to the first documentation of tumour progression
(i.e., PD) or to death due to any cause, whichever occurs earlier.
• Disease Control Rate (DCR): The rate of CR, PR or SD during Induction phase. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | Yes |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 13 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Bosnia and Herzegovina |
| India |
| Russian Federation |
| Serbia |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| End of study is performed for all subjects when the last subject reaches their EOT or passes 18 months from the enrollment. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 30 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 30 |
Print
