Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000560099
Ethics application status
Approved
Date submitted
25/06/2010
Date registered
12/07/2010
Date last updated
11/02/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Study of Nimotuzumab in Combination With Radiation Therapy in Patients With Brain Metastases from Non-Small Cell Lung Cancer (NSCLC)
Scientific title
A Randomized, Phase II, Double-Blind Study to compare the effect of Nimotuzumab Plus Whole-Brain Radiation Therapy (WBRT) versus WBRT Alone on Intracranial Disease progression in Patients with Brain Metastases from Non-Small Cell Lung Cancer
Secondary ID [1] 252084 0
YMB1000-018 (YM BioSciences Incorporated study ID)
Secondary ID [2] 252092 0
NCT00872482 (Clinicaltrials.gov)
Universal Trial Number (UTN)
U1111-1115-6263
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer with brain metastases 257631 0
Condition category
Condition code
Cancer 257807 257807 0 0
Lung - Non small cell
Cancer 257893 257893 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nimotuzumab [or h-R3, a humanized monoclonal antibody against Epidermal growth factor receptor (EGFR)] 200 mg or placebo will be diluted in a final volume of 250mL (isotonic)saline solution and administered by the intravenous route over 30 minutes weekly during radiotherapy and following whole brain radiation therapy (WBRT) until disease progression, unacceptable toxicity or withdrawal of consent. WBRT will consist of 30 Gy, in 10 fractions of 3 Gy/day over 2 weeks (5 day per week). Patients will be assessed by laboratory tests, imaging studies, standardized neurologic examination, and neurologic symptoms.
Intervention code [1] 256715 0
Treatment: Drugs
Intervention code [2] 256778 0
Treatment: Other
Comparator / control treatment
Placebo (a 10mL solution consists of Sodium dibasic phosphate, Sodium monobasic phosphate, Sodium Chloride, polysorbate and water) diluted into a total volume of 250ml of normal saline solution + Whole brain Radiation Therapy
Control group
Placebo

Outcomes
Primary outcome [1] 258677 0
Intracranial Disease progression over 6 months using magnetic resonance imaging (MRI)
Timepoint [1] 258677 0
at 6 months following randomization
Secondary outcome [1] 264682 0
Overall survival using telephone follow-ups
Timepoint [1] 264682 0
Every 3 months for upto 12 months after patient came off study.
Secondary outcome [2] 264683 0
To assess progression of intercranial disease at 2, 4 and 6 months using MRI
Timepoint [2] 264683 0
2, 4 and 6 months following randomisation
Secondary outcome [3] 264684 0
Time to neurologic progression (TNP) or death using MRI and Mini-Mental Status Examination (MMSE)
Timepoint [3] 264684 0
Every 8 weeks from randomization to disease progression
Secondary outcome [4] 264685 0
Overall survival at 6 months using medical records or telephone follow-ups.
Timepoint [4] 264685 0
6 months following randomisation
Secondary outcome [5] 264686 0
Intracranial disease progression using MRI
Timepoint [5] 264686 0
Every 8 weeks from randomization to disease progression
Secondary outcome [6] 264687 0
Time to overall disease progression using Magnetic resonance imaging (MRI) and Computed Tomography (CT)
Timepoint [6] 264687 0
Every 8 weeks from randomization to disease progression

Eligibility
Key inclusion criteria
1. Providing a written informed consent
2. Age >=18 years;
3. Histologic or cytologic confirmed diagnosis of Non-Small Cell Lung Cancer (NSCLC) of any epithelial type (squamous, adenocarcinoma, large cell, or other);
4. At least one newly diagnosed measurable metastatic lesion from NSCLC in the brain not suitable for surgical resection
5. Patient had initial diagnosis of brain metastases by image, within 8 weeks of registration
6. Karnofsky performance status (KPS) >=70;
7. Absolute neutrophil count >= 1500/mm^3;
8. Platelet count >= 50,000/mm^3;
9. Serum creatinine <=2.0 mg/dL;
10. Serum transaminases <=2 x the upper limit of normal (ULN);
11. Total serum bilirubin <=2 x ULN;
12. Lactate dehydrogenase (LDH) level <=1.3 x ULN.
13. Women of childbearing potential and men must agree to use adequate contraception (hormonal, or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in the study, she should inform her treating physician immediately
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnancy, lactation or parturition within the previous 30 days.
2. Previous WBRT.
3. Brain metastases resection with no other measurable lesion remaining.
4. Extracranial metastases in two or more organs.
5. Known leptomeningeal or subarachnoid tumor spread.
6. Plan to use radiosurgery or radiation boost after completion of WBRT.
7. Plan to use chemotherapy or any other antineoplastic modality during WBRT.
8. Previous use of an anti-EGFR drug (e.g. Tarceva, Erbitux etc.).
9. Patients receiving any other investigational agents.
10. Presence of known seropositive Human immunodeficiency virus (HIV).
11. Severe comorbidities, or other malignant neoplasm within 5 years (except adequately treated basal- or squamous-cell carcinoma of skin or in situ carcinoma of the uterine cervix).
12. Hypersensitivity or allergy to any of the drugs to be administered in this study.
13. Inability or unwillingness to complete the required assessments.
14. Geographic inaccessibility for treatment or follow-up evaluations.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All patients wil be assessed to comply with all the inclusion and exclusion criteria. Once there is confirmation of eligibility the patient will be registered. Once registered, the patient will be randomized 2:1 through an online system to receive WBRT in combination with nimotuzumab (experimental arm) or WBRT in combination with placebo (control arm), until disease progression, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first. Study allocation is concealed using central randomisation by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patient randomization in a 2:1 (experimental: control) fashion will be coordinated centrally by SciAn Services Inc. via a validated Electronic Data Capture (EDC) system. Such randomization will be performed by using the Minimization Method stratifying according to study center, recursive partitioning analysis (RPA) (1 vs. 2) and number of brain metastases (1-4 vs > 4).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/09/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
88
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA
Recruitment outside Australia
Country [1] 2711 0
Canada
State/province [1] 2711 0
Ontario
Country [2] 2712 0
United States of America
State/province [2] 2712 0
Florida
Country [3] 2713 0
Cuba
State/province [3] 2713 0
Habana
Country [4] 2714 0
Korea, Republic Of
State/province [4] 2714 0
Seodaemun-gu
Country [5] 2715 0
Canada
State/province [5] 2715 0
Alberta
Country [6] 2716 0
Canada
State/province [6] 2716 0
Quebec
Country [7] 2717 0
Canada
State/province [7] 2717 0
New Foundland
Country [8] 2718 0
Canada
State/province [8] 2718 0
British Columbia
Country [9] 2719 0
United States of America
State/province [9] 2719 0
Minnesota

Funding & Sponsors
Funding source category [1] 257193 0
Commercial sector/Industry
Name [1] 257193 0
YM BioSciences Inc.
Country [1] 257193 0
Canada
Primary sponsor type
Commercial sector/Industry
Name
YM BioSciences Inc.
Address
5045 Orbitor Drive
Building 11, Suite 400
Mississauga, Ontario
Canada L4W 4Y4
Country
Canada
Secondary sponsor category [1] 256447 0
None
Name [1] 256447 0
Address [1] 256447 0
Country [1] 256447 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259223 0
Ontario Cancer Research Ethics Board (ocreb)
Ethics committee address [1] 259223 0
Ethics committee country [1] 259223 0
Canada
Date submitted for ethics approval [1] 259223 0
Approval date [1] 259223 0
19/06/2009
Ethics approval number [1] 259223 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31327 0
Address 31327 0
Country 31327 0
Phone 31327 0
Fax 31327 0
Email 31327 0
Contact person for public queries
Name 14574 0
Wendy Chapman
Address 14574 0
5045 Orbitor Drive Building 11, Suite 400 Mississauga, Ontario Canada L4W 4Y4
Country 14574 0
Canada
Phone 14574 0
+1 905 629 9761
Fax 14574 0
+1 905 629 4959
Email 14574 0
[email protected]
Contact person for scientific queries
Name 5502 0
Dr Mark Kowalski
Address 5502 0
5045 Orbitor Drive
Building 11, Suite 400
Mississauga, Ontario
Canada L4W 4Y4
Country 5502 0
Canada
Phone 5502 0
+1 905 629 9761
Fax 5502 0
+1 905 629 4959
Email 5502 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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