A phase 4 clinical study to compare the safety and efficacy of LONQUEX® with NEULASTA® and Placebo in patients with Non-Small-Cell Lung Cancer treated with first-line chemotherapy

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2014-005096-85-LV
• Date of registration: 21/04/2015
• Prospective Registration: Yes
• Primary sponsor: Merckle GmbH
• Public title: A phase 4 clinical study to compare the safety and efficacy of LONQUEX® with NEULASTA® and Placebo in patients with Non-Small-Cell Lung Cancer treated with first-line chemotherapy
• Scientific title: Safety and Efficacy of LONQUEX® (Lipegfilgrastim) in Comparison to Pegfilgrastim (Neulasta®, Amgen Inc.) and Placebo in Patients with Non-Small-Cell Lung Cancer Receiving First-Line Chemotherapy
• Date of first enrolment: 23/04/2015
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005096-85
• 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: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Argentina, Belarus, Bosnia and Herzegovina, Brazil, Bulgaria, Chile, Croatia, Greece, Hungary, Latvia, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Turkey, Ukraine

Contacts

• Name: Biosimilar Clinical Group
• Affiliation: Merckle GmbH

• Name: Biosimilar Clinical Group
• Affiliation: Merckle GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
-Signed and dated written informed consent is obtained

-The patient is a man or woman, aged 18 to 75 years

- Patients must have a histologically or cytologically confirmed, unresectable, advanced or metastatic (Stage IIIB/IV per American Joint Committee on Cancer [AJCC] 7th edition of tumors, nodes, and metastases classification of malignant tumors [TNM] staging) squamous or non-squamous (adenocarcinoma plus large cells) NSCLC

- The patient has at least non-measurable but evaluable disease lesion per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.

- The patient is planned and eligible to receive a maximum of 6 cycles of the predefined cisplatin/pemetrexed, or cisplatin/docetaxel, or paclitaxel/cisplatin CTX

- Have a life-expectancy of at least 18 weeks, according to the investigator’s assessment

- The patient is CTX naïve. Patients who received CTX in neoadjuvant or adjuvant setting, treated >12 months ago, will be eligible

- Eastern Cooperative Oncology Group (ECOG) performance status =2

- Absolute neutrophil count (ANC) =1.5 × 109/L

- Platelets =100 × 109/L

- Adequate hepatic, cardiac, bone marrow and renal function (creatinine clearance =45 mL/min per the standard Cockroft Gault formula) for the chosen CTX (cisplatin/pemetrexed, or cisplatin/docetaxel, or paclitaxel/cisplatin) regimen.

- Women of childbearing potential (not surgically sterile or 2 years postmenopausal) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the 6 CTX cycles and for 30 days after discontinuation of study drug. Acceptable methods of contraception include intrauterine device (IUD), steroidal contraceptive (oral, implanted, transdermal, or injected), barrier method with spermicide, partner vasectomy, and abstinence throughout the study (ie, true abstinence: when this is in line with the preferred and usual lifestyle of the subject. [periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception]).

- The patient, if a man, is surgically sterile, or, if capable of producing offspring, is currently using an approved method of birth control and agrees to continued use of this method for the duration of the 6 CTX cycles (and for 90 days after taking the last dose of study drug because of the possible effects on spermatogenesis). Acceptable methods of contraception include abstinence (ie, true abstinence as detailed above), female partner’s use of an acceptable method of contraception (as described above), or if female partner is surgically sterile or 2 years post-menopausal. In addition, male patients may not donate sperm for the duration of the 6 CTX cycles and for 90 days after taking study drug.

- The patient must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period, and willing to return to the clinic for the follow-up evaluation as specified in this protocol.
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 subjects for this age range 225
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75

Exclusion criteria:
- Previous exposure to filgrastim, pegfilgrastim or lenograstim or other granulocyte colony stimulating factors (G-CSFs) in clinical development less than 6 months before randomization

- Participation in a clinical trial within 30 days or 5 half-lives of the investigational product before randomization, whichever is longer

- Known hypersensitivity to filgrastim, pegfilgrastim, lenograstim, cisplatin, pemetrexed, docetaxel or paclitaxel

- Patient meeting any contraindication for the chosen CTX regimen

- Patient to be treated with combined CTX/radiotherapy during the foreseen participation in this study

- Prior radiation therapy for lung cancer if not recovered from all toxicities related to this therapy

- Tumor surgery within 4 weeks before randomization

- Prior bone marrow or stem cell transplantation

- Progressive brain metastases

- Prior malignancy (other than NSCLC) within the preceding 5 years other than non-melanoma skin cancer or in situ cervical carcinoma

- The patient is a pregnant or lactating woman. (Any woman becoming pregnant during the study will be withdrawn from the study.)


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

Health Condition(s) or Problem(s) studied

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

Advanced squamous or non-squamous non-small-cell lung cancer (NSCLC) Stage IIIB/IV
MedDRA version: 20.0 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: PT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Trade Name: LONQUEX
Pharmaceutical Form: Solution for injection
INN or Proposed INN: LIPEGFILGRASTIM
CAS Number: 1117844-87-7
Current Sponsor code: XM22
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: NEULASTA
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PEGFILGRASTIM
CAS Number: 208265-92-3
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Secondary Objective: To explore the potential correlation between genetic polymorphisms in germline DNA specimens and response to LONQUEX® (eg, efficacy, pharmacokinetics, tolerability, and safety features) compared with placebo/comparator.

Main Objective: To collect comparative data for LONQUEX®, Neulasta® and placebo in patients with advanced squamous or non-squamous NSCLC Stage IIIB/IV, including full details of disease progression (whether or not leading to death) and mortality, for detailed clinical review.

Timepoint(s) of evaluation of this end point: After completion of the follow-up period

Primary end point(s): The primary endpoint is the progression-free survival (PFS) time (Kaplan-Meier curves, medians and hazard rates).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Safety endpoints: After completion of the follow-up period

Efficacy endpoints: cycle 1

Secondary end point(s): Secondary safety measures are:
• PFS as assessed by the investigator
• Objective response rate (ORR)
• Overall survival (OS)

Secondary Efficacy measures/endpoints:
• Duration of severe neutropenia (DSN) in cycle 1.
• Febrile neutropenia (FN) in cycle 1, defined as occurrence of at least 1 of the following conditions:
- Oral body temperature >38.5°C for at least 1 hour (2 consecutive measurements on the same day, at least 60 minutes apart) and an observed severe neutropenia (ie, ANC value <0.5 x 109/L) on the day before, on the same day or on the day after the elevated temperature readings.
- Documentation of neutropenic sepsis, ie, a sepsis in combination with an ANC value <0.5 × 109/L.
- Documentation of serious or life-threatening neutropenic infection, ie, a life-threatening infection in combination with an ANC value <0.5 × 109/L.
• Incidence of very severe neutropenia (ANC <0.1 × 109/L) in cycle 1
• Incidence of severe neutropenia (grade 4: ANC <0.5 × 109/L) in cycle 1

Secondary ID(s)

2014-005096-85-SK

XM22-ONC-40041

Source(s) of Monetary Support

Teva Pharmaceutical Industries Limited