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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01034631




Registration number
NCT01034631
Ethics application status
Date submitted
15/12/2009
Date registered
17/12/2009
Date last updated
24/05/2017

Titles & IDs
Public title
BNC105P in Combination With Everolimus/Following Everolimus For Progressive Metastatic Clear Cell Renal Cell Carcinoma
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
Secondary ID [1] 0 0
HOG GU09-145
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Everolimus
Treatment: Drugs - BNC105P

Active Comparator: Combination Arm A: Everolimus + BNC105P - Combination Arm A: Everolimus 10 mg, BNC105P MTD (from Phase 1 study) 21 day cycle

Active Comparator: Sequential Arm B:Everolimus followed by BNC105P Monotherapy - Sequential Arm B: Everolimus 10 mg, 21 day cycle
Patients to receive BNC105P monotherapy at 16 mg/m2 following progression or intolerable toxicity on everolimus therapy.


Treatment: Drugs: Everolimus
Everolimus 10 mg. Taken orally, every evening, 1 hr before or 2 hrs after meals

Treatment: Drugs: BNC105P
BNC105P, up to 16 mg/m^2

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase I: Maximum Tolerated Dose of BNC105P in Combination With Everolimus. - Phase I
Timepoint [1] 0 0
Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
Primary outcome [2] 0 0
Phase I: Toxicities of BNC105P in Combination With Everolimus. - Determine the toxicities of BNC105P in combination with everolimus. Drug-related treatment emergent adverse events by CTCAE grade 2 or greater are reported
Timepoint [2] 0 0
Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
Primary outcome [3] 0 0
Phase II: 6-month Progression Free Survival (PFS) With the Addition of BNC105P to Everolimus. - Improvement in 6-month PFS with the addition of BNC105P to everolimus. Progression is defined using RECIST criteria as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Timepoint [3] 0 0
6 months
Secondary outcome [1] 0 0
Phase I: Response Rate of BNC105P in Combination With Everolimus. - Number of objective responses per RECIST criteria. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Timepoint [1] 0 0
Until disease progression or unacceptable toxicity, up to 24 cycles or 24 months
Secondary outcome [2] 0 0
Geometric Mean Half-life of BNC105 and BNC105P in Combination With Everolimus. - Determine the PK Profile for BN105P in combination with everolimus by calculating the geometric mean half-life of BNC105P
Timepoint [2] 0 0
12 months
Secondary outcome [3] 0 0
Phase II: Response Rate With Combination Therapy Compared to Everolimus Alone - Objective response is defined as a confirmed CR or PR per RECIST criteria. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Timepoint [3] 0 0
12 months
Secondary outcome [4] 0 0
Phase II: Progression Free Survival (PFS) With BNC105P Alone in Patients After Progressing on Everolimus. - Median time to progression for arm P participants who crossed over to BNC105P monotherapy after progression. Progression is defined per RECIST criteria as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Phase II: Adverse Events of Everolimus and BNC105P When Administered as a Combination or Sequential Regimen. - Determine adverse events of everolimus and BNC105P when administered as a combination or sequential regimen. Total number of serious and non-serious adverse events for Arm A and Arm B are summarized. Complete adverse event information is supplied in the Adverse Events reporting section.
Timepoint [5] 0 0
12 months
Secondary outcome [6] 0 0
Phase II: Overall Survival - Determine overall survival probability, up to a maximum of 5 years from registration for protocol therapy.
Timepoint [6] 0 0
60 months
Secondary outcome [7] 0 0
Exploratory Objective: Correlation of PFS With Biomarkers - Exploratory analysis of serum biomarkers were undertaken to generate a potential signature for response. The correlation with 6 month progression free survival P value for four plasma biomarkers is reported.
Timepoint [7] 0 0
6 months

Eligibility
Key inclusion criteria
- Histological or cytological proof of component (any percent) of clear cell RCC (renal
cell carcinoma).

- Metastatic or locally advanced unresectable RCC. NOTE: Prior nephrectomy is not
mandatory.

- Progressive disease after 1-2 prior VEGF-directed tyrosine kinase inhibitors (TKIs).

- Measurable disease according to RECIST and obtained by imaging within 30 days prior to
registration for protocol therapy.

- Written informed consent and HIPAA authorization for release of personal health
information.

- Age > 18 years at the time of consent.

- 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 4 weeks after treatment discontinuation.

- Females of childbearing potential must have a negative pregnancy test within 7 days
prior to registration for protocol therapy.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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 =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, AE must be resolved back to baseline.

- 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. With the exception of Bevacizumab treatment, which must be completed 30
days prior to registration for protocol therapy.

- Prior radiation therapy to < 25% of the bone marrow [see bone marrow radiation chart
in the study procedure manual (SPM)] allowed if completed within 30 days prior to
registration for protocol therapy.

- Corrected QT interval (QTc) = 450 msec at least 7 days prior to registration for
protocol therapy.

- No clinically significant infections as judged by the treating investigator.

- No liver disease such as cirrhosis, chronic active hepatitis or chronic persistent
hepatitis.

- No collecting duct, medullary or sarcomatoid histology.

- 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.

- No use of full dose, therapeutic anti-coagulation with warfarin or related
anti-coagulants or unfractionated or low molecular weight heparins.

- No uncontrolled hypertension (BP >150/100mmHg despite full doses of 1
anti-hypertensive medication).

- No thrombotic event within 6 months (deep vein thrombosis, pulmonary embolism) of
registration for protocol therapy.

- No grade 2 or greater peripheral neuropathy.

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)
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 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital: Sydney Cancer Centre - Camperdown
Recruitment hospital [2] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [3] 0 0
Sydney Adventist Hospital Ltd. - Wahroonga
Recruitment hospital [4] 0 0
Gallipoli Medical Research Foundation: Greenslopes Private Hospital - Greenslopes
Recruitment hospital [5] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [6] 0 0
Princess Alexandra Hospital - Wolloongabba
Recruitment hospital [7] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [8] 0 0
Ashford Cancer Centre - Kurralta Park
Recruitment hospital [9] 0 0
Gallipoli Medical Research Foundation: Launceston General Hospital - Launceston
Recruitment hospital [10] 0 0
Peninsula Oncology Centre - Frankston
Recruitment hospital [11] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [12] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [13] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2076 - Wahroonga
Recruitment postcode(s) [4] 0 0
4120 - Greenslopes
Recruitment postcode(s) [5] 0 0
4029 - Herston
Recruitment postcode(s) [6] 0 0
4201 - Wolloongabba
Recruitment postcode(s) [7] 0 0
5000 - Adelaide
Recruitment postcode(s) [8] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [9] 0 0
7250 - Launceston
Recruitment postcode(s) [10] 0 0
3199 - Frankston
Recruitment postcode(s) [11] 0 0
3084 - Heidelberg
Recruitment postcode(s) [12] 0 0
3004 - Melbourne
Recruitment postcode(s) [13] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
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Alabama
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United States of America
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Arkansas
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California
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Colorado
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Florida
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Georgia
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Idaho
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Illinois
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Indiana
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Iowa
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Kansas
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Kentucky
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Louisiana
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Massachusetts
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Michigan
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Minnesota
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Montana
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Nebraska
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New Hampshire
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New Jersey
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New Mexico
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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Tennessee
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Texas
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Virginia
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Washington
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Wisconsin
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Singapore
State/province [35] 0 0
Singapore

Funding & Sponsors
Primary sponsor type
Other
Name
Hoosier Cancer Research Network
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Bionomics Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine whether BNC105P in combination with/following
everolimus is effective in the treatment of progressive metastatic clear cell renal cell
carcinoma following prior tyrosine kinase inhibitors.
Trial website
https://clinicaltrials.gov/show/NCT01034631
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Thomas Hutson, D.O.
Address 0 0
Hoosier Cancer Research Network
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications