Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612001245886
Ethics application status
Approved
Date submitted
25/10/2012
Date registered
26/11/2012
Date last updated
26/11/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Clinical Study Conducted in Multiple Centers Comparing Veliparib and Whole Brain Radiation Therapy (WBRT) Versus Placebo and WBRT in Subjects With Brain Metastases From Non Small Cell Lung Cancer (NSCLC)
Scientific title
A Randomized, Double-Blind, Phase 2, Dose-Ranging Study to Evaluate the Safety and Efficacy of Veliparib and Whole Brain Radiation Therapy Versus Placebo and Whole Brain Radiation Therapy in Subjects with Brain Metastases from Non-Small Cell Lung Cancer
Secondary ID [1] 281436 0
ClinicalTrials.gov NCT01657799
Universal Trial Number (UTN)
Trial acronym
M10-897
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain Metastases from Non-Small Cell Lung Cancer 287694 0
Condition category
Condition code
Cancer 288033 288033 0 0
Brain
Cancer 288034 288034 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1 - 200mg Veliparib twice daily (BID) + Whole Brain Radiation Therapy (WBRT)
Arm 2 - 50mg Veliparib BID + WBRT
Arm 3 - Placebo BID + WBRT
All Veliparib and Placebo doses are administered orally. WBRT for all 3 arms will be a total of 30.0 Gray (Gy) given in 10 daily fractions of 3.0 Gy each excluding weekends and holidays.
Veliparib/Placebo treatment will begin on the first day of WBRT. The final dose of Veliparib/Placebo will occur the day following the last day of treatment with WBRT.
Intervention code [1] 285941 0
Treatment: Drugs
Comparator / control treatment
Placebo
The placebo consists of a gelatin capsule containing Microcrystalline Cellulose.
The Placebo is administered orally BID.
The Placebo treatment will begin on the first day of WBRT. The final dose of Placebo will occur the day following the last day of treatment with WBRT.
Control group
Placebo

Outcomes
Primary outcome [1] 288239 0
Overall survival
Patient survival status will be collected at 2 month intervals for 6 months beginning at the Month 2 study visit, and every 3 months thereafter for up to 36 months. Time to death for a given patient will be defined as the number of days from the date the patient is randomised to the date of the patient's death.
Timepoint [1] 288239 0
2 month intervals for 6 months beginning at the Month 2 study visit, and every 3 months thereafter for up to 36 months
Secondary outcome [1] 299679 0
Best tumor response rate
Timepoint [1] 299679 0
Monthly intervals for 9 months for MRI tumour assessments beginning at the Month 1 study visit, and every 3 months thereafter for up to 24 months
Secondary outcome [2] 299680 0
Time to clinical brain metastasis progression
Timepoint [2] 299680 0
Monthly intervals for 9 months for Neurological assessments beginning at the Month 1 study visit, and every 3 months thereafter for up to 24 months
Secondary outcome [3] 299681 0
Time to intracranial progression (radiographic)
Timepoint [3] 299681 0
Monthly intervals for 9 months for MRI tumour assessments beginning at the Month 1 study visit, and every 3 months thereafter for up to 24 months

Eligibility
Key inclusion criteria
- Subject must have cytologically or histologically confirmed NSCLC
- Subject must have brain metastases as demonstrated on a MRI brain scan
- Subject must be eligible for treatment with WBRT
- Subject must have adequate hematologic, renal, and hepatic function
- Women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation and for a minimum of 90 days
following completion of therapy.
- Subject must be able to take oral medication
- Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subject is diagnosed with brain metastases = 21 days prior to Treatment Day 1
- Subject received any prior form of cranial radiation and/or neurosurgery for their brain metastases
- Subject's last dose of anti-cancer therapy or investigational therapy was = 7 days prior to Treatment Day 1. Subjects may continue to receive Bisphosphonates,
steroids, such as inhaled steroids for asthma, topical steroids, or replacement/stress corticosteroids, and medroxyprogesterone during the study if started prior to
treatment with veliparib/placebo and WBRT
- Subject has a Karnofsky Performance Score (KPS) of < 70
- Subject has a GPA Score of = 1.0
- Subject has clinically significant dyspnea requiring supplemental oxygen therapy
- Subject has liver metastases
- Subject has more than 2 sites (organ systems) of metastases from NSCLC with the exception of the following:
Intra-cranial sites of metastases from NSCLC; Thoracic sites of metastases from NSCLC; and Bone metastases
- Subject has leptomeningeal metastases or subarachnoid spread of tumor as demonstrated on a MRI brain scan
- Subject has unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or prior anti-cancer treatment
- Subject has a known seizure disorder that is uncontrolled, or has seizures occurring greater than or equal to 3 times a week over the past month. Subjects presenting with symptoms of seizures from the brain metastases are eligible; however he/she should receive adequate anti-seizure medication prior to study treatment
- Subject is pregnant or lactating
- Subject has previously been treated with a PARP inhibitor as an investigational agent
- Subject has clinically significant and uncontrolled major medical condition(s)
- Subject has a history of another active cancer within the past 5 years except: Cervical cancer in situ; In situ carcinoma of the bladder; Basal or squamous cell carcinoma of the skin; Or other cancer in situ that is considered cured

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)
Allocation concealment is done via central randomisation by phone /fax /computer (IVRS/WRS). Subjects who complete all Screening procedures, meet the eligibility criteria, complete the baseline neurological assessment, and quality of life and activities of daily living instruments can proceed to randomization. A subject's most recent GPA score and their neurological symptoms must be known prior to randomization and when accessing the IVRS/WRS for randomization. Subjects will be randomized in a 1:1:1 ratio with one-third of the subjects being randomized to veliparib 200 mg BID and WBRT treatment group, another one-third will be randomized to the veliparib 50 mg BID and WBRT treatment group, and the other third will be randomised to the placebo and WBRT treatment group.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomization will be stratified by GPA score (= 2.5 versus > 2.5) and neurological symptoms (symptomatic versus asymptomatic). Computer software is used to randomise using permuted block randomization method.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/09/2012
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD,SA
Recruitment postcode(s) [1] 5886 0
4029
Recruitment postcode(s) [2] 5887 0
3002
Recruitment postcode(s) [3] 5888 0
2050
Recruitment postcode(s) [4] 5889 0
5042
Recruitment postcode(s) [5] 5890 0
3220
Recruitment postcode(s) [6] 5891 0
2217
Recruitment postcode(s) [7] 5892 0
4102
Recruitment outside Australia
Country [1] 4624 0
United States of America
State/province [1] 4624 0
Country [2] 4625 0
Argentina
State/province [2] 4625 0
Country [3] 4626 0
Brazil
State/province [3] 4626 0
Country [4] 4627 0
Belgium
State/province [4] 4627 0
Country [5] 4628 0
Canada
State/province [5] 4628 0
Country [6] 4629 0
Chile
State/province [6] 4629 0
Country [7] 4630 0
Czech Republic
State/province [7] 4630 0
Country [8] 4631 0
Egypt
State/province [8] 4631 0
Country [9] 4632 0
Finland
State/province [9] 4632 0
Country [10] 4633 0
Korea, Republic Of
State/province [10] 4633 0
Country [11] 4634 0
Norway
State/province [11] 4634 0
Country [12] 4635 0
Russian Federation
State/province [12] 4635 0
Country [13] 4636 0
Spain
State/province [13] 4636 0
Country [14] 4637 0
Taiwan, Province Of China
State/province [14] 4637 0
Country [15] 4638 0
Ukraine
State/province [15] 4638 0

Funding & Sponsors
Funding source category [1] 286202 0
Commercial sector/Industry
Name [1] 286202 0
AbbVie Pty Ltd
Country [1] 286202 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
AbbVie Pty Ltd
Address
32-34 Lord St
Botany NSW 2019
Country
Australia
Secondary sponsor category [1] 285013 0
None
Name [1] 285013 0
Address [1] 285013 0
Country [1] 285013 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288275 0
Royal Brisbane and Women's Hospital Human Research Ethics Committee
Ethics committee address [1] 288275 0
Ethics committee country [1] 288275 0
Australia
Date submitted for ethics approval [1] 288275 0
Approval date [1] 288275 0
26/06/2012
Ethics approval number [1] 288275 0
HREC/12/QRBW/150

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

Contacts
Principal investigator
Name 34870 0
Address 34870 0
Country 34870 0
Phone 34870 0
Fax 34870 0
Email 34870 0
Contact person for public queries
Name 18117 0
Lesley Werth
Address 18117 0
32-34 Lord St
Botany NSW 2019
Country 18117 0
Australia
Phone 18117 0
+61 2 9384 9700
Fax 18117 0
+61 2 9384 9802
Email 18117 0
[email protected]
Contact person for scientific queries
Name 9045 0
Address 9045 0
Country 9045 0
Phone 9045 0
Fax 9045 0
Email 9045 0

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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.