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Trial registered on ANZCTR


Registration number
ACTRN12610001073099
Ethics application status
Approved
Date submitted
1/12/2010
Date registered
6/12/2010
Date last updated
25/06/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Pilot Study of a Steroid Sulphatase Inhibitor
(BN83495) in Patients Receiving an Oral Epidermal
Growth Factor Receptor Tyrosine Kinase Inhibitor
(EGFR-TKI) for the Treatment of Non-Small Cell Lung
Cancer (NSCLC)
Scientific title
A Pilot Study of a Steroid Sulphatase Inhibitor
(BN83495) in Patients Receiving an Oral Epidermal
Growth Factor Receptor Tyrosine Kinase Inhibitor
(EGFR-TKI) for the Treatment of Non-Small Cell Lung
Cancer (NSCLC)
Secondary ID [1] 253214 0
HREC ID: 10/51
Universal Trial Number (UTN)
Trial acronym
BN83495
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 258743 0
Skin Rash 258744 0
Condition category
Condition code
Cancer 258895 258895 0 0
Lung - Non small cell
Skin 258896 258896 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BN83495 Dosage and Administration
BN83495 (also known as STX64 and 667-coumate) is a first in class inhibitor of steroid sulphatase (STS), currently in clinical development to target steroid dependent cancers. STS converts oestrone sulphate to oestrone, a precursor of oestradiol and dehydroepiandrosterone sulphate (DHEA-S) to dehydroepiandrosterone (DHEA), a precursor of adrenal testosterone.
The oral dose of BN83495 is 40 mg daily, fasted (30 minutes before breakfast), given in the morning. BN83495 will be taken for 12 weeks.

BN83495 will be supplied by Ipsen Pty Ltd as tablets packed into conventional blister strips (10 tablets/blister).

EGFR-TKI Dosage and Administration

The EGFR-TKI used in this study will be either Erlotinib or Gefitinib which will be taken for 12 weeks.

The oral dose of erlotinib is 150 mg daily, taken at least one hour before or two hours after the ingestion of food.

The oral dose of gefitinib is 250mg daily, taken at least one hour before or two hours after the ingestion of food.

In stratum A, patients with NSCLC requiring treatment with an EGFR-TKI will be pre-treated with BN83495 for 3 days prior to starting the EGFR-TKI. In stratum B, patients already on an EGFR-TKIwill receive BN83495. All patients will continue to receive BN83495 for a period of 12 weeks, and be followed for these 12 weeks to determine the impact of treatment on existing skin condition.
Intervention code [1] 257689 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 259752 0
The frequency and grade of papulo-pustular rash in patients with non-small cell lung cancer (NSCLC) receiving an EGFR-TKI and BN83495.

To be assessed by medical review and photographs of the patient's skin - and graded based on CTC criteria.
Timepoint [1] 259752 0
After 12 weeks of treatment
Primary outcome [2] 259753 0
The frequency and grade of additional cutaneous (side) effects in patients with NSCLC receiving an EGFR-TKI and BN83495.

To be assessed by medical review and grading based on CTC criteria - cutaneous side effects that are commonly experienced by patients on EGFR-TKIs eg. paronychia, trichomegaly, dry skin, hair thinning, skin cracks.
Timepoint [2] 259753 0
After 12 weeks of treatment
Secondary outcome [1] 268513 0
The side effect profile of the combination (BN83495 + an EGFR-TKI).

To be assessed by medical review and grading based on CTC criteria.
Timepoint [1] 268513 0
After 12 weeks of treatment
Secondary outcome [2] 268514 0
Changes in oestrogen, androgen-related biochemistry and EGFR-TKI blood levels associated with the combination (BN83495 + EGFR-TKI).
Timepoint [2] 268514 0
After 12 weeks of treatment

Eligibility
Key inclusion criteria
1. Patients with histologically documented, unresectable, locally advanced, recurrent or metastatic (Stage IIIB or Stage IV) NSCLC who are otherwise eligible for treatment with an EGFR-TKI (erlotinib or gefitinib), or who are already receiving an EGFR-TKI.
2. Patients who are scheduled to receive, or are already receiving a standard dose EGFR-TKI.
3. The presence of any EGFR-TKI -related rash in patients already on treatment must be grade 2 or less.
4. Male or female patients aged 18 years or over who weigh 40kg or more.
5. ECOG performance status of 0 – 2, inclusive.
6. Granulocyte count =1.5 x 109/L and platelet count >100 x 109/L.
7. Serum bilirubin must be =1.5 x upper limit of normal (ULN). ALT must be = 2 x ULN.
8. Serum creatinine =1.5 ULN or creatinine clearance =60 ml/min.
9. Able to comply with study and follow-up procedures. Patients must be willing to be photographed.
10. a) Female patient of childbearing potential must have a negative pregnanacy test within one week prior to study entry OR have been amenorrhoeic for at least two years.
b) All patients of reproductive potential must agree to use birth control for the duration of the study. This is only required for as long as the patient has reproductive potential. The type of birth control is a decision which should be made between the treating physician and the patient.
11. Patient has given written, informed consent to participate in the study.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who cannot take oral medication.
2. Patients with prior prostate, breast or endometrial cancer unless in remission for = 5 years.
3. Patients receiving other hormonally active agents.
4. Pregnancy or lactation.
5. Concurrent or recent history (within the last 3 months) of significant skin disease, not related to EGFR-TKI therapy.
6. Concurrent use of systemic or topical glucocorticoids (apart from intranasal and inhaled corticosteroids to treat rhinitis and asthma, respectively), for patients starting both an EGFR-TKI and BN83495. Patients already receiving an EGFR-TKI and topical glucocorticoids as part of their management are allowed.
7. Concurrent use of systemic carbonic anhydrase II inhibitors (e.g.acetazolamide, dichlorphenamide,methazolamide)
8. Serious illness or medical condition that precludes the safe administration of the trial treatment including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
9. Patients unwilling or unable to comply with protocol and patients with a history of non-compliance or inability to grant informed consent.
10. Current participation in another clinical trial using an investigational agent.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 258160 0
Hospital
Name [1] 258160 0
Division of Cancer Medicine
Address [1] 258160 0
Peter MacCallum Cancer Centre
Locked Bag # 1, A'Beckett St
Melbourne, VIC, 8006
Country [1] 258160 0
Australia
Primary sponsor type
Individual
Name
Professor John Zalcberg
Address
Peter MacCallum Cancer Centre
St Andrew Pl East Melbourne, VIC 3002
Country
Australia
Secondary sponsor category [1] 257336 0
Hospital
Name [1] 257336 0
Centre for Biostatistics and Clinical Trials
Address [1] 257336 0
10 St Andrew Pl
East Melbourne, VIC 3002
Country [1] 257336 0
Australia

Ethics approval
Ethics application status
Approved

Summary
Brief summary
Patients who have been diagnosed with non-small cell lung cancer may receive, or already be receiving treatment with a drug called Erlotinib or Gefitinib. Erlotinib and Gefitinib are similar drugs that belong to a class of drugs that inhibit a specific biological receptor, called the Epidermal Growth Factor Receptor (EGFR), which is over expressed in a number of different cancers. One of the potential side effects of Erlotinib and Gefitinib is skin rash, which occurs in up to 75% of patients. In this study, we will investigate whether treatment with a new drug, BN83495, can reduce the severity and/or frequency with which this rash occurs.

BN83495 is an experimental drug, which is taken as a tablet, and is being tested as a possible anti-cancer treatment. The drug inhibits steroid production and is being developed by Ipsen Pty Ltd. Excess steroid production in the skin has also been linked to the development of acne and skin rashes. Therefore, it is our hypothesis that BN83495 pre-treatment may complement the use of erlotinib or gefitinib and reduce the severity of rash. This project will be performed at the Peter MacCallum Cancer Centre and will involve approximately 10 to 20 patients. The aim of this project is to measure the frequency and severity of skin rash, and other side-effects, for patients treated with Erlotinib or Gefitinib and BN83495. Changes in the drugs and hormones bllod levels will also be measured. Patients will be assessed at Peter MacCallum Cancer Centre weekly for a period of 12 weeks from the first day of treatment with BN83495.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31974 0
Dr Dr Linda Mileshkin
Address 31974 0
Peter MacCallum Cancer Centre
Locked Bag # 1, A'Beckett St
Melbourne, VIC, 8006, Australia
Country 31974 0
Australia
Phone 31974 0
+61 3 96561111
Fax 31974 0
Email 31974 0
Linda.Mileshkin@petermac.org
Contact person for public queries
Name 15221 0
Dr Dr Bereha Khodr
Address 15221 0
Centre for Biostatistics & Clinical Trials Peter MacCallum Cancer Centre Level 2, 10 St Andrews Place East Melbourne, VIC 3002, Australia
Country 15221 0
Australia
Phone 15221 0
+61 3 9656 5826
Fax 15221 0
+61 3 9656 1420
Email 15221 0
bereha.khodr@petermac.org
Contact person for scientific queries
Name 6149 0
Dr Dr Linda Mileshkin
Address 6149 0
Peter MacCallum Cancer Centre
Locked Bag # 1, A'Beckett St
Melbourne, VIC, 8006
Country 6149 0
Australia
Phone 6149 0
+61 3 9656 1697
Fax 6149 0
Email 6149 0
linda.mileshkin@petermac.org

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary