Nab-Paclitaxel to Paclitaxel in Advanced Urothelial Cancer Progressing on or After Platinum Containing Regimen.

Urothelial Cancer Clinical Trial

Official 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02033993
• Other study ID #: BL12
• Status: Completed
• Phase: Phase 2
• Start date: March 11, 2014
• Est. completion date: October 28, 2020

Study information

• Verified date: October 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Nab-paclitaxel is a formulation of the chemotherapeutic drug paclitaxel that is combined with a human protein called albumin. In Canada, nab-paclitaxel is currently approved for the treatment of metastatic breast cancer. This drug has been tested in other cancers and has shown promising activity in lung cancer, melanoma and pancreatic cancer. Information from research studies suggests that nab-paclitaxel may be a useful treatment for urothelial cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 199
• Est. completion date: October 28, 2020
• Est. primary completion date: May 3, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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.

Related Conditions & MeSH terms

• Urothelial Cancer

Intervention

Drug:
• Nab-Paclitaxel

• Paclitaxel

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Townsville Hospital	Douglas	Queensland
Australia	St Vincents Hospital Melbourne	Fitzroy	Victoria
Australia	Frankston Hospital	Frankston	Victoria
Australia	Peninsula Oncology Centre	Frankston	Victoria
Australia	University Hospital Geelong	Geelong	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Ashford Cancer Care Research	Kurralta Park	South Australia
Australia	Nambour General Hospital	Nambour	Queensland
Australia	Royal Perth Hospital (renamed to Fiona Stanley Hospital)	Perth	Western Australia
Australia	Port Macquarie Base Hospital	Port Macquarie
Australia	Epworth Healthcare Freemasons Hospital	Richmond	Victoria
Australia	Western Hospital (renamed to Footscray Hospital)	St Albans	Victoria
Australia	Concord Cancer Centre	Sydney	South Australia
Australia	Liverpool Hospital	Sydney	South Australia
Australia	Prince of Wales Hospital	Sydney	South Australia
Australia	Border Medical Oncology (Murray Valley Private Hospital)	Wodonga	Victoria
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Hopital Charles LeMoyne	Greenfield Park	Quebec
Canada	QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	The Jewish General Hospital	Montreal	Quebec
Canada	The Research Institute of the McGill University	Montreal	Quebec
Canada	Stronach Regional Health Centre at Southlake	Newmarket	Ontario
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	University Health Network	Toronto	Ontario
Canada	Centre hospitalier regional de Trois-Rivieres	Trois-Rivieres	Quebec
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Canadian Cancer Trials Group	Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Celgene

Countries where clinical trial is conducted

Australia,  Canada, 

References & Publications (1)

Sridhar SS, Blais N, Tran B, Reaume MN, North SA, Stockler MR, Chi KN, Fleshner NE, Liu G, Robinson JW, Mukherjee SD, Rahim Y, Winquist E, Booth CM, Nguyen NT, Beardsley EK, Alimohamed NS, McDonald GT, Ding K, Parulekar WR. Efficacy and Safety of nab-Pacl — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival	PFS is defined as the time from randomization to the first observation of disease progression or death due to any cause.	42 months
Secondary	Overall Survival	Time from randomization to the date of death due to any causes, or censored at last contact date.	42 months
Secondary	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.	42 months
Secondary	Time to Response	Time from the date of randomkization to the date of objective response according to RECIST Response Criteria was first achieved.	42 months
Secondary	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.	42 months