Transitional Cell CarcinomaPhase 2/3CabB1NCT01668459
Treatment of Locally Advanced or Metastatic Transitional Cell Carcinoma With Cabazitaxel
A Phase 2/3 study testing Cabazitaxel in people with Transitional Cell Carcinoma, run by Dr Anjali Zarkar at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transitional Cell Carcinoma
- What is being tested?
- Cabazitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2013to Nov 2017
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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:
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- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospitals Birmingham
Birmingham, B15 2TH
About this study
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.
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.
Read the 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.
- Conditions
- Transitional Cell Carcinoma
- Being tested
- Cabazitaxel, Best Supportive Care
- Keywords
- Transitional cell carcinoma, Bladder cancer, Cancer, Oncology, Cabazitaxel
- Medical subject headings
- Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabazitaxelDrug
Also called Jevtana, XRP6258, RPR116258A
25 mg/m2, IV (in the vein) on day 1 of each 21 day cycle. Number of Cycles: maximum 6
Best Supportive CareOther
Best Supportive Care including single agent chemotherapy as determined by the patient's study physician
| Study group | Role | What they receive |
|---|---|---|
| Cabazitaxel | Experimental | 6 cycles (3 weekly) of 25 mg/m^2 IV infusion Receives: Drug: Cabazitaxel |
| Best Supportive Care | Other | Best supportive care including single agent chemotherapy as determined by the patient's study doctor Receives: Other: Best Supportive Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
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.
Measured: Change from baseline at Week 9 and Week 18
Secondary outcomes (3)
Overall survival
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.
Measured: 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
Quality of Life
QOL will be assessed by using a validated instrument; the EuroQOL (EQ-5D).
Measured: Change from baseline at Week 6, Week 12, Week 18, Week 21
Safety and tolerability
Dose delays and dose reductions, adverse events, laboratory safety data
Measured: From date of randomisation up to 30 days after final dose of study medication
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2012 (estimated)
- Study startJan 2013
- Primary completionNov 2017
- Study completionNov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transitional Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr Anjali Zarkar
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Sponsor-investigator, Dr Anjali Zarkar, University Hospital Birmingham NHS Foundation Trust
- Investigators
- Anjali Zarkar, Principal investigator, University Hospitals Birmingham NHS FT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01668459
- Sponsor's protocol ID
- RRK4368
- Other IDs
- 2012-002552-16
- Acronym
- CabB1
- Status last verified
- Nov 2018
- First submitted
- 13 Aug 2012
- Last updated
- 4 Dec 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01668459
- Acronym / sponsor ID
- CabB1 / RRK4368
- Conditions
- Transitional Cell Carcinoma
- Keywords
- Transitional cell carcinoma, Bladder cancer, Cancer, Oncology, Cabazitaxel
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Dr Anjali ZarkarUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- Jan 2013
- Primary completion
- Nov 2017 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 20 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cabazitaxel | Experimental | Drug: Cabazitaxel6 cycles (3 weekly) of 25 mg/m^2 IV infusion |
| Best Supportive Care | Other | Other: Best Supportive CareBest supportive care including single agent chemotherapy as determined by the patient's study doctor |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (19 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CabazitaxelAlso: Jevtana, XRP6258, RPR116258A25 mg/m2, IV (in the vein) on day 1 of each 21 day cycle. Number of Cycles: maximum 6 | Drug | Cabazitaxel |
| Best Supportive CareBest Supportive Care including single agent chemotherapy as determined by the patient's study physician | Other | Best Supportive Care |
Primary outcome
Overall response rate
Time frame: Change from baseline at Week 9 and Week 18
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.
3 secondary outcomes
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
Quality of Life
Time frame: Change from baseline at Week 6, Week 12, Week 18, Week 21
Safety and tolerability
Time frame: From date of randomisation up to 30 days after final dose of study medication
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anjali Zarkar principal investigator
University Hospitals Birmingham NHS FT
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Cabazitaxel in people with Transitional Cell Carcinoma, run by Dr Anjali Zarkar at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (time frame: Change from baseline at Week 9 and Week 18). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2018.