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Trial registered on ANZCTR


Registration number
ACTRN12613000063718
Ethics application status
Approved
Date submitted
20/12/2012
Date registered
17/01/2013
Date last updated
28/08/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Phase I/II Study of BNC105P in Combination with Everolimus or Following Everolimus For Progressive Metastatic Clear Cell Renal Cell Carcinoma Following Prior Tyrosine Kinase
Inhibitors. Hoosier Oncology Group GU09-145
Scientific title
Phase I/II Study of BNC105P in Combination with Everolimus or Following Everolimus For Progressive Metastatic Clear Cell Renal Cell Carcinoma Following Prior Tyrosine Kinase
Inhibitors. Hoosier Oncology Group GU09-145
Secondary ID [1] 281601 0
Clinicaltrials.gov: NCT01034631
Universal Trial Number (UTN)
NONE
Trial acronym
N/A
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Clear cell renal cell carcinoma 287884 0
Condition category
Condition code
Cancer 288259 288259 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm A: Everolimus 10mg Daily, BNC105P 16mg/m2 infusion on Day 1 and Day 8 of a 21 day cycle (combination arm). Drugs used on Arm A are given simultaneously: everolimus by oral administration daily, BNC105P by IV administration (on days 1 and 8 of a repeating 21 day cycle).

Arm B: This is a sequential Arm. Arm B subjects are administered Everolimus at 10mg per day by oral administration until disease progression or unacceptable toxicity is observed (then Everolimus is ceased). Once this occurs, patients have the option to enter BNC105P only portion of Arm B. BNC105P given by IV administration at 16mg/m2 (on days 1 and 8 of a repeating 21 day cycle).
Intervention code [1] 286133 0
Treatment: Drugs
Comparator / control treatment
Everolimus alone. Patients receive Everolimus alone on treatment arm B at 10mg orally on a daily basis. This continues until disease progression or unacceptable toxicity is observed. At this time, Everolimus is ceased. At this point, patients have the optin to enter the sequential portion of Arm B which is BNC105P alone, given at 16mg/m2 via IV on day 1 and 8 of a 21 day cycle.
Control group
Active

Outcomes
Primary outcome [1] 288437 0
Improvement in 6-month progression free survival (PFS) with the addition of BNC105P to everolimus.
Recist defined tumor assessment. Measurement from the start of the treatment until the criteria for disease progression is met (or death occurs), taking as reference the smallest measurements recorded since the treatment started. The time to progression, in patients with documented disease progression at their first disease evaluation, will be considered the time between initiation of therapy and the date of first documentation of disease progression. The percentage of patients whom have achieved Progression Free Survival (PFS) at 6 months will be calculated.
Timepoint [1] 288437 0
Every 9 weeks for 2 years from registration for protocol therapy, every 6 months for years 3 - 5 for up to a
maximum of 5 years from registration to protocol therapy
Secondary outcome [1] 300160 0
To determine PFS with BNC105P alone in patients progressing on everolimus.
Recist defined tumor assessment. Measurement from the start of the treatment until the criteria for disease progression is met (or death occurs), taking as reference the smallest measurements recorded since the treatment started. The time to progression, in patients with documented disease progression at their first disease evaluation, will be considered the time between initiation of therapy and the date of first documentation of disease progression.
Timepoint [1] 300160 0
Every 9 weeks for 2 years from registration for protocol therapy, every 6 months for years 3- 5 for up to a
maximum of 5 years from registration to protocol therapy
Secondary outcome [2] 300161 0
To evaluate the adverse events of the combination. Clinical assessments will in part be used to confirm adverse events. Adverse events will be categorized according to the Common Terminology Criteria for Adverse Events (CTCAE) as listed by the National Cancer Institute of the USA. Adverse events summaries are provided with the consent documentation and protocol documentation.
Timepoint [2] 300161 0
Day 1 and Day 8 of every cycle
Secondary outcome [3] 300162 0
To determine the overall survival, up to a maximum of 5 years from registration for protocol therapy.
The overall survival time for each patient is the number of days from the day of first treatment to the earlier of (1) death (from any cause) and (2) the last date of patient contact. If the survival time does not correspond to the patient’s death then it is treated as censored.
Timepoint [3] 300162 0
Every 9 weeks for 2 years from registration for protocol therapy, every 6 months for years 3-5 for up to a
maximum of 5 years from registration to protocol therapy
Secondary outcome [4] 300441 0
To determine response rate with combination therapy compared to everolimus alone.
The objective response rate is the proportion of all patients with confirmed Partial Response or Complete Response according to RECIST, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).
Timepoint [4] 300441 0
Statistical analysis at end of study.

Eligibility
Key inclusion criteria
Written informed consent and HIPAA authorization for release of personal
health information.
NOTE: HIPAA authorization may be included in the informed consent orobtained separately.
Age > or equal to 18 years at the time of consent.
Karnofsky Performance Score (KPS) > or equal to 70 within 7 days prior to registration for protocol therapy.
Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 8 weeks after treatment discontinuation.
Females of childbearing potential must have a negative pregnancy test
within 7 days prior to registration for protocol therapy. NOTE:
Females are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal
ligation, or bilateral oophorectomy) or they are postmenopausal.
Females must not be breastfeeding.
Histological or cytological proof of component (any percent) of clear cell RCC (renal cell carcinoma). NOTE: No component of collecting duct or medullary histology is allowed. Up to 30% sarcomatoid histology will be permitted.
Metastatic or locally advanced unresectable RCC. NOTE: Prior
nephrectomy is not mandatory
Progressive disease after 1-2 prior VEGF-directed tyrosine kinase inhibitors
(TKIs). NOTE: Patients who did not tolerate a VEGF-directed TKI may also be considered for entry to the trial. The Sponsor is to be consulted in such cases.
Prior treatment with more than 2 VEGF-directed TKIs will be permitted
in the phase I component of the study.
Measurable disease according to RECIST and obtained by imaging within 30 days prior to registration for protocol therapy.
Prior cancer treatment must be completed at least 14 days prior to registration for protocol therapy and the patient must have recovered from the acute toxic effects of the regimen.
At least 30 days must have elapsed prior to registration following major
surgery (opening of a body cavity – chest, abdomen or cranium), or at least 7 days prior to registration for minor surgery.
Prior radiation therapy to <25% of the bone marrow [see bone marrow radiation chart in the study procedure manual (SPM)] allowed if
completed within 14 days prior to registration for protocol therapy.
Corrected QT interval (QTc) < or equal to 450 msec within 7 days prior to registration
for protocol therapy. NOTE: if (QTc) is >450 and < or equal to 500 msec, subject to local cardiology review and approval, the patient may be enrolled if the QTc elevation is deemed clinically insignificant.
NOTE: Laboratory values must be obtained within 7 days prior to
registration for protocol therapy.
White blood cell count (WBC) >or equal to 3.5 K/ mm3
Hemoglobin (Hgb) > or equal to 8.5 g/dL
Platelets > or equal to 100 K/ mm3
Absolute neutrophil count (ANC) > or equal to 1.5 K/ mm3
Serum Creatinine <2.5 x ULN (upper limit normal)
Total Bilirubin < and equal to 1.25 x ULN
Aminotransferase (AST and ALT) < or equal to 2.5 × ULN
INR <1.5 ULN
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
No clinically significant infections as judged by the treating investigator
No liver disease such as cirrhosis, chronic active hepatitis or chronic
persistent hepatitis
No prior treatment with temsirolimus or everolimus in the phase II component of the study NOTE: Prior treatment with these agents is permitted in the phase I component of the study. In those cases where everolimus is being used immediately prior to study entry, a washout period will not be required.
No use of full dose, therapeutic anti-coagulation with warfarin or related anti-coagulants or unfractionated or low molecular weight heparins.
NOTE: Low dose warfarin for catheter prophylaxis or acetylsalicylic acid < equal to 325 mg/day is acceptable.
No uncontrolled hypertension, BP >150/100mmHg despite use of antihypertensive medication(s).
No thrombotic event within 6 months (deep vein thrombosis, pulmonary
embolism) of registration for protocol therapy.
No significant cardiovascular events within 6 months (CVA, CAD, peripheral arterial obstruction, arrhythmias, cardiac dysfunction) of registration for protocol therapy
No history of clinical CHF or LVEF <50% by Echo (or MUGA) within 30
days prior to registration for protocol therapy.
No grade 2 or greater peripheral neuropathy.
No active brain metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis within 30 days prior to registration on protocol therapy.
NOTE: A patient with prior brain metastasis are eligible if they have completed their radiation treatment for brain metastasis > or equal to 30 days prior to registration for
protocol therapy, are off steroids, and are asymptomatic.
No other currently active malignancy.
No treatment with any investigational agent within 14 days prior to registration for protocol therapy. NOTE: If treated with investigational agent within 14 days prior to registration patients AE must be resolved back to baseline.

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)
The randomization process for GU09-145 is based on a randomized block design. Six block randomization lists were created by a statistician, one for each combination of the stratification factors. Once the stratification factors are entered in the EDC system, the next arm assignment is selected by the software. The process is completely random within the block as the software always selects the next available arm assignment from the appropriate list.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not 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
Active, not recruiting
Date of first participant enrolment
Anticipated
3/05/2010
Actual
21/09/2011
Date of last participant enrolment
Anticipated
Actual
18/06/2013
Date of last data collection
Anticipated
Actual
Sample size
Target
134
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC
Recruitment postcode(s) [1] 6061 0
2000,
Recruitment postcode(s) [2] 6062 0
4000
Recruitment postcode(s) [3] 6063 0
3000
Recruitment postcode(s) [4] 6064 0
5000
Recruitment postcode(s) [5] 6065 0
7000
Recruitment outside Australia
Country [1] 4696 0
United States of America
State/province [1] 4696 0

Funding & Sponsors
Funding source category [1] 286407 0
Commercial sector/Industry
Name [1] 286407 0
Bionomics Pty Ltd
Country [1] 286407 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Bionomics Pty Ltd
Address
32 Dalgliesh Street
Thebarton
South Australia
5031
Country
Australia
Secondary sponsor category [1] 285192 0
Commercial sector/Industry
Name [1] 285192 0
Hoosier Oncology Group
Address [1] 285192 0
351. W. 10th Street, Suite 330, Indianapolis, IN 46202
Country [1] 285192 0
United States of America
Other collaborator category [1] 277230 0
Commercial sector/Industry
Name [1] 277230 0
CPR Pharma Pty Ltd
Address [1] 277230 0
Suite C, 32 West Thebarton Road, Thebarton, South Australia, 5031
Country [1] 277230 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288484 0
Austin Health
Ethics committee address [1] 288484 0
Ethics committee country [1] 288484 0
Australia
Date submitted for ethics approval [1] 288484 0
Approval date [1] 288484 0
25/09/2012
Ethics approval number [1] 288484 0
HREC/12/Austin/73

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

Contacts
Principal investigator
Name 34995 0
Dr Thomas Hutson
Address 34995 0
Director, GU Oncology Program
Texas Oncology, PA
Baylor Sammons Cancer Center
Dallas, Texas
46202
Country 34995 0
United States of America
Phone 34995 0
+1 214 370 1000
Fax 34995 0
Email 34995 0
[email protected]
Contact person for public queries
Name 18242 0
Kari Hill
Address 18242 0
32C West Thebarton Road
Thebarton, South Australia, 5031
Country 18242 0
Australia
Phone 18242 0
+61 8 8125 1925
Fax 18242 0
+61 8 8354 3146
Email 18242 0
[email protected]
Contact person for scientific queries
Name 9170 0
Jose Iglesius
Address 9170 0
Chief Medical Officer
Bionomics
31 Dalgleish St.
Thebarton (Adelaide), SA 5032
AUSTRALIA
Country 9170 0
Australia
Phone 9170 0
+1 (416) 618-1729
Fax 9170 0
n.a
Email 9170 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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