A Phase III Trial to Compare the Effectiveness, Safety and action of HD204 (study drug) in comparison to Avastin�® in patients with Metastatic or Recurrent Non-squamous Non-small Cell Lung Cancer (cancer of the lungs)
- Conditions
- Health Condition 1: C399- Malignant neoplasm of lower respiratory tract, part unspecified
- Registration Number
- CTRI/2019/09/021090
- Lead Sponsor
- Prestige BioPharma Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
1. Able and willing to give written informed consent.
2. Aged � 18 years of age.
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 and
life expectancy >3 months based on Investigatorââ?¬•s judgement.
4. Histologically confirmed metastatic Stage IV or recurrent non-squamous non-small cell lung cancer (NSCLC) that is no longer amendable to curative surgery or local therapy.
5. At least one measurable lesion according to RECIST v.1.1. as confirmed by CIR; bone-only and brain-only metastases are not allowed. Lesions previously treated with radiotherapy are non-target lesions unless clear progression was documented.
Previous results are acceptable if performed within 4 weeks prior to screening.
6. No first line treatment for metastatic or recurrent disease. Prior systemic therapy
and/or radiotherapy for locally advanced disease is permitted if completed > 6 months prior to the diagnosis of relapsing disease.
7. Tumors without EGFR mutation or ALK receptor alteration. Patients with unknown mutation status or known EGFR mutation or ALK receptor alteration may be included provided the corresponding targeted agent is not available and chemotherapy is the standard of care of the study center.
8. Adequate hematological function, defined as:
a. Platelet count: >100,000/�¼L without the need for transfusion in the 2 weeks
prior to Screening.
b. Prothrombin time (PT), International normalized ratio (INR) or activated partial thromboplastin time (aPTT) �1.5 x the upper limit of normal (ULN).
c. Absolute neutrophil count: >1,500/�¼L without any medical interventional treatment (ie, granulocyte-colony stimulating factors [G-CSFs] and/or herbal remedies).
d. Hemoglobin: >9 g/dL, without the need for transfusion in the 2 weeks prior to Screening.
9. Adequate hepatic function as evidenced by meeting all of the following requirements:
a. Total bilirubin: <1.5 x ULN.
b. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP): <3 x ULN.
c. If liver metastases are present, ALT or AST <5 x ULN; if liver and/or bone metastases are present ALP <5 x ULN.
10. Adequate renal function, as evidenced by meeting all of the following requirements:
a. Serum creatinine <1.5 x ULN and creatinine clearance > 50 mL/minute or estimated glomerular filtration rate (GFR) >50 mL/minute.
b. Urine dipstick for proteinuria of less than 2+ (other ways of urinalysis are also acceptable); if urine dip stick is > 2+, proteinuria must be < 2 g in 24 hours or an equivalent protein/creatinine ratio of <2000 mg/g creatinine (or < 226.0 mg/mmoL creatinine).
11. Female patients with child bearing potential (excluding women who have undergone surgical sterilization or menopause. Menopause is defined as the status where no menstrual periods continue for 1 year or more without any other medical reasons), are eligible if they have negative serum pregnancy testing within 7 days prior to first dosing and are willing to use an effective method of birth control/contraception to prevent pregnancy until 6 months after the end of study. Male patients must consent using effective method of contraception until 6 months
after the end of study.
Note: Contraceptive methods that are considered highly effective are
1Diagnosisofsmallcellcarcinomaofthelungormixedtumorsincludingsmallcellcarcinoma.2Known ROS-1 positive tumor.3Tumorcavitation,tumorinvadinginto large blood vessels or close to large vessels
with high risk of bleeding,according to PI judgment.4Prior therapy with monoclonal antibodies or small molecule inhibitors against VEGF or VEGFR.5Prior systemic anticancer therapy or radiotherapy for locally advanced nsNSCLC if
completed <6 months prior to the diagnosis of relapsing disease.6Previous malignancy other than NSCLC in the last 5 yrs except for basal cell cancer of the skin or pre-invasive cancer of the cervix.7Known brain metastasis or other CNS metastasis that is either symptomatic or
untreated. Metastases that have been treated by complete resection and/or radiotherapy demonstrating stability or improvement are not an exclusion criterion provided they are stable as shown by computed tomography (CT) or magnetic
resonance imaging (MRI) scan for at least 4 weeks before Screening without evidence of cerebral edema. Patients on stable dose of corticosteroids or anticonvulsants arepermitted.8Any unresolved toxicity > Grade I (except alopecia) from previous anticancer therapy (including radiotherapy).9History of hemoptysis ( > 1/2 teaspoon per event over the past 6 months) or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding. Clinically
non-significant minor bleeding is acceptable.10A significant thrombotic or hemorrhagic event <6 months prior to Screening (includes hemoptysis [ > 2.5 mL of red blood],gastrointestinal bleeding, hematemesis, CNShemorrhage, severe epistaxis or vaginal bleeding,cerebral infarction,transient
ischemic attacks, myocardial infarction, angina,uncontrolled coronary artery disease).11 Clinically serious non-healing wounds,or incompletely healed bone fracture at screening.12 Known hypersensitivity to any of the study drugs or their excipients, or history of clinically significant atopic allergy (eg,asthma including childhood asthma,urticarial).13Live/attenuated vaccine within 12 weeks prior to the Screening Visit.14History of myocardial infarction ( <6 months prior to Screening), unstable angina, New
York Heart Association Grade II or greater, congestive heart failure, or serious cardiac
arrhythmia requiring medication.15History of poorly controlled hypertension or resting blood pressure >150/100 mmHgin the presence of a stable regimen of antihypertensive therapy.16Any major surgical procedure (risk of bleeding or wound healing complications) within 28 days prior to the screening.17History of active gastroduodenal ulcer, abdominal fistula as well as no gastrointestinalfistula,gastrointestinal perforation or intra-abdominal abscess within
6 months prior to Screening.18Clinically significant active infection requiring systemic therapy.19Known active Hepatitis B infection (according to local site standards) or active
Hepatitis C infection (Hepatitis C virus [HCV] antibody positive)the patient could be
included in the study if he/she is HCV RNA negative.20Known human immunodeficiency virus (HIV) infection (positive results from patient
history are accepted),syphilis,or active tuberculosis infection.21Patient considered unsuitable for inclusion by the Investigator (eg, inability tounderstand and/or comply with study requirements or presence of any condition,which, in the opinion of the Investigat
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To demonstrate clinical equivalence of the bevacizumab biosimilar (HD204) to reference bevacizumab (EU-Avastin�®) given with chemotherapy by comparing the overall response rate (ORR) at Week 12 in Patients with Metastatic or RecurrentNon-squamous Non-small Cell Lung Cancer.Timepoint: Week 12
- Secondary Outcome Measures
Name Time Method To compare ORR at Week 6 and Week 18 between the bevacizumab biosimilar (HD204) <br/ ><br>and reference bevacizumab (EU-Avastin�®). Time point: at Week 6 and Week 18 <br/ ><br>â�¢ To compare ORR at Week 12 adjusted on dose intensity. Time point: at Week 12 <br/ ><br>â�¢ To compare the efficacy of bevacizumab biosimilar (HD204) to reference bevacizumab <br/ ><br>(EU-Avastin�®) in terms of duration of response (DoR), progression-free survival (PFS) <br/ ><br>and overall survival (OS). Time point: throughout the study <br/ ><br>Timepoint: To compare the safety and immunogenicity of bevacizumab biosimilar (HD204) and <br/ ><br>reference bevacizumab (EU-Avastin�®). Time point: throughout the study <br/ ><br>â�¢ To compare bevacizumab Ctrough after administration of bevacizumab biosimilar <br/ ><br>(HD204) and reference bevacizumab (EU-Avastin�®). Time point: throughout the study <br/ ><br>