The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02033993




Registration number
NCT02033993
Ethics application status
Date submitted
9/01/2014
Date registered
13/01/2014
Date last updated
14/04/2020

Titles & IDs
Public title
Nab-Paclitaxel to Paclitaxel in Advanced Urothelial Cancer Progressing on or After Platinum Containing Regimen.
Scientific title
A Multicentre Randomized Phase II Trial Comparing Nab-Paclitaxel to Paclitaxel in Patients With Advanced Urothelial Cancer Progressing on or After a Platinum Containing Regimen.
Secondary ID [1] 0 0
BL12
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Urothelial Cancer 0 0
Condition category
Condition code

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

Active Comparator: Arm 1 - Nab-Paclitaxel - 260mg/m2: q21 days

Active Comparator: Arm 2 - Paclitaxel - 175mg/m2: q21 days


Treatment: Drugs: Nab-Paclitaxel


Treatment: Drugs: Paclitaxel


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

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival - PFS is defined as the time from randomization to the first observation of disease progression or death due to any cause.
Timepoint [1] 0 0
42 months
Secondary outcome [1] 0 0
Overall Survival - Time from randomization to the date of death due to any causes, or censored at last contact date.
Timepoint [1] 0 0
42 months
Secondary outcome [2] 0 0
Clinical Benefit Rate - Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started. Clinical Benefit Rate = OR + SD > 12 weeks.
Timepoint [2] 0 0
42 months
Secondary outcome [3] 0 0
Time to Response - Time from the date of randomkization to the date of objective response according to RECIST Response Criteria was first achieved.
Timepoint [3] 0 0
42 months
Secondary outcome [4] 0 0
Health Related Quality of Life Evaluated Using EORTC-C15-Pal - Quality of life will be assessed using the EORTC-C15-PAL questionnaire plus additional study specific questions.
Changes in quality of life scores while on treatment (compared to baseline scores) will be examined using descriptive analyses and inferential statistics. The primary test to compare treatment arms will be the NCIC CTG Quality of Life Committee suggested response analyses. A change score of 10 points from baseline was defined as clinically relevant. Patients were considered improved if reported a score 10-points or better than baseline at any time point in QoL assessment. Conversely, patients were considered worsened if reported a score minus 10-points or worse than baseline at any time point in QOL assessment without the above-defined improvement being observed. Patients whose scores were between 10-point changes from baseline at every QoL assessment were considered as stable.
Timepoint [4] 0 0
42 months

Eligibility
Key inclusion criteria
- Histologically or cytologically confirmed diagnosis of TCC of the urinary tract
(bladder, urethra, ureter, renal pelvis) and metastatic or locally advanced inoperable
disease extent (T4, N2, N3 or M1 disease)

Note: Mixed histologies (except small cell) permitted if predominately TCC by IHC.

- Patients must have evidence of metastatic disease, but measurable disease is not
mandatory. To be considered evaluable for the overall response rate (complete and
partial response), patients must have at least one measurable lesion as follows:

- X-ray, physical exam = 20 mm

- Conventional CT scan, MRI = 20 mm

- Spiral CT scan = 10 mm

- Male or female, 18 years of age or older.

- ECOG performance status = 2 at study entry

- Adequate hematological, renal and hepatic functions as defined by the following
required laboratory values obtained within 14 days prior to randomization. If anemic,
patients should be asymptomatic and should not be decompensated.

- Absolute neutrophil count (ANC) = 1.5 x10^9/L (1,500 cells/mm3)

- Platelet count = 90 x10^9/L (100,000/mm3)

- Hemoglobin = 90 g/L

- Calculated creatinine clearance > 25 mL/min (Cockcroft and Gault formula)

- Total bilirubin = 1.5 times the upper limit of normal (= 2.5X if Gilbert's
disease)

- ALT (SGPT) = 3 x ULN or = 5 x ULN if hepatic metastases are present

- Patients may have had prior neoadjuvant or adjuvant therapy for completely resected
disease, provided it was completed at least 12 months prior to randomization. Patients
must have recovered from any acute toxic effects to = Grade 2 from any prior
treatments. Neoadjuvant or adjuvant chemotherapy will be considered to have been first
line therapy in the metastatic setting if the patient progressed within 12 months of
the last dose.

- Patients must have received one and only one prior chemotherapeutic regimen which
included a platinum (at least one cycle) for metastatic/recurrent disease. Treatment
must have been discontinued at least 4 weeks prior to randomization in this study.
Patients must have recovered from any acute toxic effects to = Grade 2 from any prior
treatments

- Patients may not have had any prior therapy with a taxane in any setting.

- Patients may have had prior investigational agents but these must have been
discontinued at least 4 weeks prior to randomization. Patients must have recovered
from any acute toxic effects to = Grade 2 from any prior treatments.

- Prior treatments with radiation therapy in the adjuvant and/or metastatic setting are
permitted provided that at least 2 weeks have elapsed since the last fraction of
radiation therapy and all treatment related adverse events are = Grade 1 at the time
of randomization.

- Patients may have had prior surgery provided that at least 4 weeks elapsed between the
end of surgery and randomization onto the study. Patients must have recovered from any
acute toxic effects to = Grade 2 from any prior treatments.

- Patients may have peripheral neuropathy from previous treatments providing that it is
= Grade 1.

- Patient is able (i.e. sufficiently fluent) and willing to complete the health and
demographic, quality of life, and health utilities questionnaires in either English or
French. The baseline assessment must be completed within required timelines, prior to
registration/randomization. Inability (illiteracy in English or French, loss of sight,
or other equivalent reason) to complete the questionnaires will not make the patient
ineligible for the study. However, ability but unwillingness to complete the
questionnaires will make the patient ineligible.

- Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements. Each patient must sign a consent form prior to enrollment in
the trial to document their willingness to participate.

- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
test within 7 days prior to randomization. In addition to routine contraceptive
methods, "effective contraception" also includes heterosexual celibacy and surgery
intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined
as a hysterectomy, bilateral oophorectomy, bilateral tubal ligation or
vasectomy/vasectomized partner. However, if at any point a previously celibate patient
chooses to become heterosexually active during the time period for use of
contraceptive measures outlined in the protocol, he/she is responsible for beginning
contraceptive measures.

- Patients must be accessible for treatment and follow up. Patients registered on this
trial must be treated and followed at the participating centre. This implies there
must be reasonable geographical limits (for example: 1 ½ hour's driving distance)
placed on patients being considered for this trial. Investigators must assure
themselves the patients registered on this trial will be available for complete
documentation of the treatment, adverse events, response assessment and follow-up.

- In accordance with CCTG policy, protocol treatment is to begin within 5 working days
of patient randomization.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- A candidate for potentially curative surgery or radiotherapy.

- Patients with brain metastases are ineligible if they meet at least one of the
following criteria:

1. diagnosis within 3 months from randomization

2. untreated brain metastases

3. unstable brain metastasis as defined by:

- cavitation or hemorrhage in the brain lesion

- symptomatic state

- daily prednisone or equivalent use greater than 10 mg

Patients do not need CT/MRI scans to rule out brain metastases unless there is a clinical
suspicion of CNS metastases.

- Patients with serious illness or medical condition which would not permit the patient
to be managed according to the protocol including, but not limited to:

1. . any evidence of severe or uncontrolled systemic disease (i.e. known cases of
hepatitis B or C or human immunodeficiency virus (HIV)).

2. patients with active or uncontrolled infections.

Screening for chronic conditions is not required, although patients known to have
such conditions at screening should not be included.

- Women who are pregnant or breastfeeding.

- Patients with history of allergic or hypersensitivity reactions to any study drug or
their excipients or with a history of allergic reactions attributed to compounds with
similar chemical composition to any of the study drugs.

- Planned concomitant participation in another clinical trial of an experimental agent,
vaccine or device. Concomitant participation in observational studies is acceptable.

- Patients with a history of other malignancies, except: adequately treated non-melanoma
skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
curatively treated with no evidence of disease for = 5 years. Prior prostate cancer is
allowed provided that it is an incidental finding at cystoprostatectomy with a PSA
<0.5 ng/mL at randomization or a prior diagnosis of low risk prostate cancer at any
time as defined by =T2, a Gleason Score of 6 or less and PSA <10 ng/mL.

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 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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)
QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Townsville Hospital - Douglas
Recruitment hospital [2] 0 0
Nambour General Hospital - Nambour
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 0 0
Ashford Cancer Care Research - Kurralta Park
Recruitment hospital [5] 0 0
Prince of Wales Hospital - Sydney
Recruitment hospital [6] 0 0
Concord Cancer Centre - Sydney
Recruitment hospital [7] 0 0
Liverpool Hospital - Sydney
Recruitment hospital [8] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [9] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [10] 0 0
St Vincents Hospital Melbourne - Fitzroy
Recruitment hospital [11] 0 0
Frankston Hospital - Frankston
Recruitment hospital [12] 0 0
Peninsula Oncology Centre - Frankston
Recruitment hospital [13] 0 0
University Hospital Geelong - Geelong
Recruitment hospital [14] 0 0
Epworth Healthcare Freemasons Hospital - Richmond
Recruitment hospital [15] 0 0
Western Hospital (renamed to Footscray Hospital) - St Albans
Recruitment hospital [16] 0 0
Border Medical Oncology (Murray Valley Private Hospital) - Wodonga
Recruitment hospital [17] 0 0
Royal Perth Hospital (renamed to Fiona Stanley Hospital) - Perth
Recruitment hospital [18] 0 0
Port Macquarie Base Hospital - Port Macquarie
Recruitment postcode(s) [1] 0 0
4814 - Douglas
Recruitment postcode(s) [2] 0 0
4560 - Nambour
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park
Recruitment postcode(s) [4] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [5] 0 0
2031 - Sydney
Recruitment postcode(s) [6] 0 0
2139 - Sydney
Recruitment postcode(s) [7] 0 0
2170 - Sydney
Recruitment postcode(s) [8] 0 0
7000 - Hobart
Recruitment postcode(s) [9] 0 0
3128 - Box Hill
Recruitment postcode(s) [10] 0 0
3065 - Fitzroy
Recruitment postcode(s) [11] 0 0
3199 - Frankston
Recruitment postcode(s) [12] 0 0
3320 - Geelong
Recruitment postcode(s) [13] 0 0
3121 - Richmond
Recruitment postcode(s) [14] 0 0
3021 - St Albans
Recruitment postcode(s) [15] 0 0
3690 - Wodonga
Recruitment postcode(s) [16] 0 0
6150 - Perth
Recruitment postcode(s) [17] 0 0
2444 - Port Macquarie
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Alberta
Country [2] 0 0
Canada
State/province [2] 0 0
British Columbia
Country [3] 0 0
Canada
State/province [3] 0 0
Nova Scotia
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Canada
State/province [5] 0 0
Quebec
Country [6] 0 0
Canada
State/province [6] 0 0
Saskatchewan

Funding & Sponsors
Primary sponsor type
Other
Name
Canadian Cancer Trials Group
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Celgene
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to compare the effects on urothelial cancer of nab-paclitaxel
compared to paclitaxel to treat this disease.

This research is being done because currently there is no effective treatment for urothelial
cancer that has progressed after prior chemotherapy.
Trial website
https://clinicaltrials.gov/show/NCT02033993
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Srikala Sridhar
Address 0 0
Univ. Health Network-Princess Margaret Hospital, Toronto, Ontario Canada
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