Treatment of Locally Advanced or Metastatic Transitional Cell Carcinoma With Cabazitaxel (CabB1)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University Hospital Birmingham NHS Foundation Trust
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Dr Anjali Zarkar, University Hospital Birmingham NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01668459
First received: August 13, 2012
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

A study for patients with confirmed locally advanced or metastatic Transitional Cell Carcinoma of the bladder or upper urinary tracts who have developed progressive disease within 12 months of their platinum based chemotherapy. The study aims to compare the overall response rate of cabazitaxel treatment versus best supportive care including single agent chemotherapy.


Condition Intervention Phase
Transitional Cell Carcinoma
Drug: Cabazitaxel
Other: Best Supportive Care
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cabazitaxel in Platinum Pre-treated Patients With Locally Advanced or Metastatic Transitional Cell Carcinoma Who Developed Disease Progression Within 12 Months of Platinum Based Chemotherapy.

Resource links provided by NLM:


Further study details as provided by University Hospital Birmingham NHS Foundation Trust:

Primary Outcome Measures:
  • Overall response rate [ Time Frame: Change from baseline at Week 9 and Week 18 ] [ Designated as safety issue: No ]
    To compare the overall response rate of patients administered cabazitaxel vs best supportive care (including single agent chemotherapy) in patients with transitional cell carcinoma who have previously progressed on a platinum-based regimen.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: From date of randomisation to the date of tumour progression or death (from any cause) (or survival at study cut-off date), whichever came first up to 12months after the final patient has completed study treatment ] [ Designated as safety issue: No ]
    Defined as the time interval from the date of randomization to the date of death due to any cause. In absence of confirmation of death, survival time will be censored at the earlier of the last date the patient is known to be alive and the study cut-off date.

  • Quality of Life [ Time Frame: Change from baseline at Week 6, Week 12, Week 18, Week 21 ] [ Designated as safety issue: No ]
    QOL will be assessed by using a validated instrument; the EuroQOL (EQ-5D).

  • Safety and tolerability [ Time Frame: From date of randomisation up to 30 days after final dose of study medication ] [ Designated as safety issue: Yes ]
    Dose delays and dose reductions, adverse events, laboratory safety data


Estimated Enrollment: 96
Study Start Date: January 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cabazitaxel
6 cycles (3 weekly) of 25 mg/m^2 IV infusion
Drug: Cabazitaxel
25 mg/m2, IV (in the vein) on day 1 of each 21 day cycle. Number of Cycles: maximum 6
Other Name: Jevtana, XRP6258, RPR116258A
Best Supportive Care
Best supportive care including single agent chemotherapy as determined by the patient's study doctor
Other: Best Supportive Care
Best Supportive Care including single agent chemotherapy as determined by the patient's study physician

Detailed Description:

Bladder cancer was the 9th most common cause of cancer worldwide in 2002. About 70% of patients have superficial tumour and 30% have invasive tumour at diagnosis. Patients with superficial tumour are treated by surgery, which is the only curative treatment. However, about 50% of these patients will relapse, and cannot be cured by local treatment in the majority of cases. The survival of untreated metastatic patients does not exceed 3 to 6 months, and systemic chemotherapy increases overall survival of patients with unresectable disease.

However, the overall survival of patients with advanced disease treated with chemotherapy remains short (14 months), which reflects a substantial unmet medical need for more effective therapy in this very poor prognosis disease.

Cabazitaxel is a new taxane, taxanes have demonstrated activity in advanced bladder cancer, and are among the most active new cytotoxic agents to be assessed in transitional cell carcinoma.

Cabazitaxel has demonstrated activity in cell lines with acquired resistance to doxorubicin, vincristine, vinblastine, paclitaxel, and docetaxel.

This is a randomised, open-label, parallel-group phase 2 study of cabazitaxel versus best supportive care (including chemotherapy).

The study is divided into three phases: screening, treatment, and follow-up. The treatment phase comprises a maximum of six three-weekly cycles of therapy, with a post treatment discontinuation visit taking place 3 weeks after last dose of treatment before the follow-up phase begins.

This phase 2 study will initially recruit 25 patients and after interim analysis will to increase to recruit 96 patients randomised between the two treatment options and the study is expected to last about 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Age ≥ 18
  • Life expectancy ≥ 12 weeks
  • Patients with histology/cytology confirmed Transitional Cell Carcinoma (TCC) including mixed pathology with predominantly TCC, with locally advanced (T4b) or metastatic (lymph node or visceral) TCC arising from bladder or upper urinary tracts.
  • Treated patients with incidental prostate cancer (pT2, Gleason ≤ 6) and PSA (Prostate Specific Antigen) ≤ 0.5 ng/mL are eligible
  • Measurable disease as per RECIST Criteria 1.1
  • ECOG Performance Status 0-1.
  • Previously received first line platinum based treatment.
  • Recurrence within 12 months (by RECIST criteria version 1.1) from last cycle of chemotherapy.

Exclusion Criteria:

  • Previous therapy with a taxane.
  • Pure non TCC histologies
  • Grade II or more peripheral neuropathy
  • Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeks prior to enrolment in the study.
  • Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus)
  • Inadequate organ and bone marrow function as evidenced by:

    • Hemoglobin < 9.0 g/dL
    • Absolute neutrophil count < 1.5 x 109/L,
    • Platelet count < 100 x 109/L,
    • AST/SGOT and/or ALT/SGPT > 2.5 x ULN;
    • Total bilirubin > 1.0 x ULN,
    • Serum creatinine > 1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance ≤ 30 mL/min should be excluded (see Appendix 6 for formula)
  • Symptomatic brain metastases or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system involvement).
  • History of another neoplasm except non-metastatic melanoma skin cancers, carcinoma in situ of the cervix, or cancer cured by surgery, small field radiation or chemotherapy < 5 years prior to randomization.
  • History of inflammatory bowel disease, significant bowel obstruction.
  • History of hypersensitivity to platinum, gemcitabine, taxanes, Polysorbate-80, or to compounds with similar chemical structures.
  • Any of the following events within 6 months prior to randomization: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft surgery, clinically symptomatic and uncontrolled cardiovascular disease, or clinically significant arrhythmias (grade 3-4).
  • Concurrent treatment with strong inhibitors of cytochrome P450 3A4 or patients planning to receive these treatments. For patients who were receiving treatment with such agents, a one-week washout period is required prior to randomization.
  • Women who are breastfeeding and women of child bearing potential (not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus)) unless in agreement to use an adequate method of contraception during the treatment period and for 6 months after the last dose of the study drug. Men unless in agreement that they will use effective contraception (and condom to protect against exposure to seminal liquid) whilst participating in the trial and for 6 months after the last dose of study medication.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01668459

Contacts
Contact: Anjali Zarkar, MD MBBS +44 121 371 3559 anjali.zarkar@uhb.nhs.uk
Contact: Amanda Davies, BSc (Hons) +44 121 204 1794 amanda.davies@uhb.nhs.uk

Locations
United Kingdom
University Hospitals Birmingham Recruiting
Birmingham, United Kingdom, B15 2TH
Principal Investigator: Anjali Zarkar, MRCP MD FRCR         
Sub-Investigator: Nicholas James, MBBSFRCP PhD         
Sponsors and Collaborators
Dr Anjali Zarkar
Sanofi
Investigators
Principal Investigator: Anjali Zarkar University Hospitals Birmingham NHS FT
  More Information

No publications provided

Responsible Party: Dr Anjali Zarkar, Oncology Consultant, University Hospital Birmingham NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01668459     History of Changes
Other Study ID Numbers: RRK4368, 2012-002552-16
Study First Received: August 13, 2012
Last Updated: January 23, 2013
Health Authority: United Kingdom: National Health Service

Keywords provided by University Hospital Birmingham NHS Foundation Trust:
Transitional cell carcinoma
Bladder cancer
Cancer
Oncology
Cabazitaxel

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on August 27, 2014