Efficacy and safety of XM22 in patients with non small cell lung cancer receiving cisplatin / etoposide chemotherapy

ISRCTN	ISRCTN55761467
DOI	https://doi.org/10.1186/ISRCTN55761467
Secondary identifying numbers	XM22-04

Submission date: 22/04/2010
Registration date: 10/06/2010
Last edited: 16/01/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Peter Bias
Scientific

Merckle GmbH
A Member of the ratiopharm Group
Clinical Research
Graf-Arco-Straße 3
Ulm
89075
Germany

Study information

Study design	Multinational multicentre randomised double blind placebo controlled phase III study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Efficacy and safety of XM22 in patients with non small cell lung cancer receiving cisplatin / etoposide chemotherapy. A multinational, multicentre, randomised, double-blind placebo-controlled study
Study objectives	Demonstration of superiority of XM22 versus placebo when administered for up to a maximum of four cycles chemotherapy (CTX) in patients with non small cell lung cancer (NSCLC)
Ethics approval(s)	At each study centre, the protocol (dated 01/10/2009) and informed consent form for this study were reviewed and approved by Independent Ethic Committees before inclusion of patients. Amendments to the protocol will be reviewed and approved in the same manner before being implemented
Health condition(s) or problem(s) studied	NSCLC patients with chemotherapy induced neutropenia
Intervention	XM22: 1 syringe 6 mg per cycle (cycles 1-4) Placebo: 1 syringe per cycle (cycles 1-4) The duration of the study will be 12 weeks. The duration of follow up will be 360 days.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	XM22
Primary outcome measure	Incidence of febrile neutropenia (FN) in the first cycle of chemotherapy
Secondary outcome measures	1. Incidence of febrile neutropenia in cycles 2, 3 and 4 and across all cycles 2. Duration and incidence of severe neutropenia, defined as grade 4 neutropenia with an ANC <0.5 x 109/L in cycles 1, 2, 3 and 4 3. Duration and incidence of very severe neutropenia, defined as ANC <0.1 x 109/L in cycles 1, 2, 3 and 4 4. Depth of ANC nadir in all cycles 5. Time to ANC nadir in cycles 1, 2, 3 and 4 6. Time to ANC recovery in all cycles 7. Percentage of actually delivered vs. scheduled cumulative chemotherapy dose 8. Proportion of patients with chemotherapy doses reduced, omitted, or delayed 9. Number of days of delay of chemotherapy 10. Overall quality of life as measured by the EORTC QLQ-C30 (version 3) and the EORTC QLQ-LC13 11. Time in hospital and time in intensive care unit due to febrile neutropenia or connected infections 12. Incidence of treatment with i.v. antibiotics due to FN or connected infections 13. Incidence of patients requiring prophylactic open treatment
Overall study start date	01/05/2010
Completion date	01/03/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	375 (250 XM22 group, 125 placebo group)
Key inclusion criteria	1. Provide signed and dated written informed consent 2. Men and women aged ≥18 3. The patient must be able to understand and follow instructions and must be able to participate in the study for the entire period 4. Patients with NSCLC stage IIIB/IV, histologically or cytologically documented 5. Patients planned and eligible to receive 4 cycles of the predefined cisplatin / etoposide-based, myelosuppressive CTX 6. Life-expectancy of at least 4 months 7. CTX naïve 8. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 9. Absolute Neutrophil Count (ANC) ≥1.5 x 109/L 10. Platelet count ≥100 x 109/L 11. Adequate hepatic function, i.e. ALT and AST <2.5 x ULN, alkaline phosphatase <5 x ULN, bilirubin <ULN 12. Adequate renal function, i.e. creatinine <1.5 x ULN 13. Adequate hepatic, cardiac, bone marrow and renal function for the chosen CTX regimen
Key exclusion criteria	1. Participation in a clinical trial within 30 days before randomisation. 2. Previous exposure to filgrastim, pegfilgrastim or lenograstim or other G-CSFs in clinical development less than 6 months before randomisation. 3. Known hypersensitivity to filgrastim, pegfilgrastim, lenograstim, cisplatin or etoposide. 4. Patient planned for non-myelosuppressive CTX. 5. Patients with an individual high risk for febrile neutropenia in respect of the cisplatin/etoposide CTX according to the assessment of the investigator. Risk factors are age >65 years, low performance status, poor nutritional status, and liver, renal or cardiovascular disease. 6. Patient meeting any contraindication for the chosen CTX regimen. 7. Treatment with systemically active antibiotics within 72 hours before CTX. 8. Treatment with lithium at inclusion or planned during the entire study. 9. Patient to be treated with combined chemo-/ radiotherapy during the foreseen participation in this study. 10. Chronic use of oral corticosteroids (except low dose chronic treatment with ≤20 mg/day prednisolone or equivalent dose for chronic obstructive pulmonary disease). 11. Prior radiation therapy or tumour surgery within 4 weeks before randomisation. 12. Prior bone marrow or stem cell transplantation. 13. Prior malignancy within the preceding 5 years other than non-melanoma skin cancer or in situ cervical carcinoma. 14. Any illness or condition that in the opinion of the investigator may affect the safety of the patient or the evaluation of any study endpoint. 15. Pregnant or nursing women. Women of child bearing potential who do not agree to use a highly effective method of birth control during the entire duration of the study. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs, sexual abstinence or vasectomised partner. Female patients will be considered to be of child-bearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years (Postmenopausal is defined as the time after which a woman has experienced twelve consecutive months of amenorrhea without a period).
Date of first enrolment	01/05/2010
Date of final enrolment	01/03/2012

Locations

Countries of recruitment

Belarus
Bosnia and Herzegovina
Bulgaria
Germany
Poland
Romania
Russian Federation
Serbia
Ukraine

Study participating centre

Merckle GmbH

Ulm
89075
Germany

Sponsor information

BioGeneriX AG (Germany)
Industry

High-Tech-Park Neckarau
Janderstraße 3
Mannheim
68199
Germany

Website	http://www.biogenerix.com
"ROR"	https://ror.org/03xa4xh46

Funders

Funder type

Industry

BioGeneriX AG (Germany)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	03/07/2015	16/01/2019	Yes	No
Results article	results	01/12/2016	16/01/2019	Yes	No

Editorial Notes

16/01/2019: Publication references added.