Advanced Urothelial Cancer of Bladder After Failure of Platinum-containing Therapy.Phase 1/2NCT01265940
Pazopanib and Vinflunine in Urothelial Cancer of the Bladder
A Phase 1/2 study testing Pazopanib as add-on to vinflunine in people with Advanced Urothelial Cancer of Bladder After Failure of Platinum-containing Therapy., run by Prof. Dr. Thomas Otto at 1 site in Germany.
Trial summary
Urothelial carcinoma of the bladder mostly is chemically induced and represents the second prevalent urooncological disease. About 20% of newly diagnosed urothelial carcinoma cases of the bladder are already advanced or metastasized. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Urothelial Cancer of Bladder After Failure of Platinum-containing Therapy.
- What is being tested?
- Pazopanib as add-on to vinflunine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteGermany
- Study dates
- Mar 2011to Aug 2012
- Phase
- Phase 1/2
- 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 years
- Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) with lymphatic (N-stage 2-3) and/or distant metastases (M-stage 1) not amenable to definitive regional/local therapy
- Progression of tumor disease after platinum containing systemic chemotherapy for advanced or metastatic disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 1
- estimated minimal life expectancy of 3 months at screening
Show all 9Show fewer
- At least one measurable tumor lesion according to RECIST 1.1 criteria
- Adequate organ system function at screening
- Adequate contraception
Who cannot join
- More than 1 prior chemotherapy, biologic therapy or hormonal therapy within 14 days prior to the first dose of study medication
- Prior malignancy within 5 years prior to inclusion (exception: successfully treated basal cell carcinoma or in situ carcinoma)
- History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis
- Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding within 28 days prior to beginning study treatment, e.g
- Active peptic ulcer disease
- Known intraluminal metastatic lesion/s with risk of bleeding
Show all 38Show fewer
- Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
- History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess
- Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product, e.g.
- Malabsorption syndrome
- Major resection of the stomach or small bowel
- Active infection requiring antibiotics within 14 days before registration
- Corrected QT interval (QTc) > 480 msecs using Bazett's formula at screening
- Screening-electrocardiogram (ECG) with any significant modifi¬cations suggesting a high risk of occurrence of an acute clinical event (such as signs of angina pectoris, high risk arrhythmia etc.)
- History of one or more of the following cardiac / cardiovascular conditions within the past 6 months before registration:
- Cardiac angioplasty or stenting
- Myocardial infarction
- Unstable angina
- Coronary artery bypass graft surgery
- Symptomatic peripheral vascular disease
- NYHA Class II, III or IV congestive heart failure
- Uncontrolled cardiac arrhythmia
- Poorly controlled hypertension, defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90 mmHg
- History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months before registration
- Peripheral neuropathy grade ≥ 2 (NCI CTC v3.0)
- Unstable diabetes mellitus
- Uncontrolled hypercalcaemia > 2.9 mmol/L
- Prior major surgery or trauma within 28 days prior to registration and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major)
- Evidence of active bleeding e.g. GI bleeding or bleeding diathesis at screening.
- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
- Hemoptysis with bleeding of > 2.5 mL within 8 weeks before registration
- Any serious and/or unstable pre-existing medical, psychiatric/psychological, familial, sociological, geographical or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
- prior to the first dose of study drug and for the duration of the study
- Radiation, surgery or tumor embolization or any investigational treatment within 14 days prior to the first dose of study medication
- Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or progressing in severity, except nausea, vomiting, alopecia
- ASA 4
- Pre-treatment with Pazopanib or Vinflunine
- Pregnancy or lactation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Target-specific Therapy With Pazopanib as Add-on to Vinflunine in Patients With Advanced or Metastatic Urothelial Carcinoma of the Bladder After Failure of Platinum-based Treatment
Urothelial carcinoma of the bladder mostly is chemically induced and represents the second prevalent urooncological disease. About 20% of newly diagnosed urothelial carcinoma cases of the bladder are already advanced or metastasized. Before 2008 2009 no second line therapy after failure of primary systemic therapy of advanced / metastatic disease was established outside of clinical trials. The actual standard for this situation was a supportive, symptomatic therapy. Vinflunine has demonstrated improved survival from 4.3 to 6.9 months (p=0.04), with an adequate disease control, good symptom control and with acceptable toxicity. Based on these results, this compound became standard se¬cond line treatment for refractory metastatic bladder cancer disease after failure of platinum-containing therapy. As the prognosis still remains poor, new treatment opportunities have to be explored.
The target-specific therapy with Pazopanib suggests a positive influence of both inductive and perioperative treatment of solid tumors. Pazopanib has been approved by the FDA and the EMA for the treatment of advance renal cell carcinoma. Results for advanced urothelial carcinoma are missing so far as well as data on tolerability of the combination of both vinflunine and pazopanib. As the pharmacodynamic properties as well as the safety profile of both drugs are different, assumption is justified that there might occur additive efficacy effects without addition of adverse outcomes. Aim of the study thus is
Read more
- To define the maximum tolerated dose (MTD) of Pazopanib in combination with Vinflunine in a phase-I-setting and
- To further assess efficacy and safety of the combination at the MTD level in phase II.
During the pase-I-part of the study different doses of pazopanib will be added to the standard vinflunine scheme in groups of 6 patients maximum. Dose escalation will only be performed in the next patient group if not more than one out of six patients shows dose-limiting toxicity. Each patient will be treated with the drug combination for a duration of two vinflunine cycles, that is six weeks.
During the phase-II study new patients will be treated with the drug combination at maximum-tolerated dose until disease progression (assessed by RECIST 1.1 procedures).
- Being tested
- Pazopanib as add-on to vinflunine
- Keywords
- bladder cancer, urothelial cancer, metastatic urothelial cancer, advanced urothelial cancer
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pazopanib as add-on to vinflunineDrug
Also called Pazopanib is marketed as Votrient., Vinflunine is marketed as Javlor.
Patients will receive vinflunine standard regimen (intravenous infusion every three weeks) as specified per drug label plus additional pazopanib as daily oral medication. Doses of pazopanib will be escalated in 200 mg/d steps during phase I up to a maximum of 800 mg/d.
In Phase II the patients will be given pazopanib + vinflunine at maximum tolerated dose.
| Study group | Role | What they receive |
|---|---|---|
| Pazopanib + Vinflunine | Experimental | Not described Receives: Drug: Pazopanib as add-on to vinflunine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Definition of the Maximum Tolerated Dose (MTD) of Pazopanib in combination with Vinflunine.
MTD ist defined as the dose level with dose-limiting toxicity occurring in maximum one out of six patients.
Measured: 6 weeks (two cycles of vinflunine)
Phase II: Progression-free survival rate
Progression-free survival will be assessed by means of RECIST 1.1. methodology
Measured: 3 months
Secondary outcomes (1)
Phase I: Progression-free survival rate, Phase II: Safety profile, overall survival
Progression-free survival will be assessed by means of RECIST 1.1. methodology
Measured: Six weeks after first administration of study drug.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2010 (estimated)
- Study startMar 2011
- Primary completionJan 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Urothelial Cancer of Bladder After Failure of Platinum-containing Therapy.Studies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prof. Dr. Thomas Otto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Prof. Dr. Thomas Otto, Lukas-Krankenhaus GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01265940
- Sponsor's protocol ID
- DZITM1
- Status last verified
- Oct 2012
- First submitted
- 22 Dec 2010
- Last updated
- 10 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Target-specific Therapy With Pazopanib as Add-on to Vinflunine in Patients With Advanced or Metastatic Urothelial Carcinoma of the Bladder After Failure of Platinum-based Treatment
- ClinicalTrials.gov ID
- NCT01265940
- Acronym / sponsor ID
- DZITM1
- Keywords
- bladder cancer, urothelial cancer, metastatic urothelial cancer, advanced urothelial cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Prof. Dr. Thomas OttoUniversity, hospital or other
- Study start
- Mar 2011
- Primary completion
- Jan 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 23 Dec 2010 (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.
Urothelial carcinoma of the bladder mostly is chemically induced and represents the second prevalent urooncological disease. About 20% of newly diagnosed urothelial carcinoma cases of the bladder are already advanced or metastasized. Before 2008 2009 no second line therapy after failure of primary systemic therapy of advanced / metastatic disease was established outside of clinical trials. The actual standard for this situation was a supportive, symptomatic therapy. Vinflunine has demonstrated improved survival from 4.3 to 6.9 months (p=0.04), with an adequate disease control, good symptom control and with acceptable toxicity. Based on these results, this compound became standard se¬cond line treatment for refractory metastatic bladder cancer disease after failure of platinum-containing therapy. As the prognosis still remains poor, new treatment opportunities have to be explored.
The target-specific therapy with Pazopanib suggests a positive influence of both inductive and perioperative treatment of solid tumors. Pazopanib has been approved by the FDA and the EMA for the treatment of advance renal cell carcinoma. Results for advanced urothelial carcinoma are missing so far as well as data on tolerability of the combination of both vinflunine and pazopanib. As the pharmacodynamic properties as well as the safety profile of both drugs are different, assumption is justified that there might occur additive efficacy effects without addition of adverse outcomes. Aim of the study thus is
- To define the maximum tolerated dose (MTD) of Pazopanib in combination with Vinflunine in a phase-I-setting and
- To further assess efficacy and safety of the combination at the MTD level in phase II.
During the pase-I-part of the study different doses of pazopanib will be added to the standard vinflunine scheme in groups of 6 patients maximum. Dose escalation will only be performed in the next patient group if not more than one out of six patients shows dose-limiting toxicity. Each patient will be treated with the drug combination for a duration of two vinflunine cycles, that is six weeks.
During the phase-II study new patients will be treated with the drug combination at maximum-tolerated dose until disease progression (assessed by RECIST 1.1 procedures).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pazopanib + Vinflunine | Experimental | Drug: Pazopanib as add-on to vinflunine |
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 years
- Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) with lymphatic (N-stage 2-3) and/or distant metastases (M-stage 1) not amenable to definitive regional/local therapy
- Progression of tumor disease after platinum containing systemic chemotherapy for advanced or metastatic disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 1
Key exclusion criteria (38 listed)
- More than 1 prior chemotherapy, biologic therapy or hormonal therapy within 14 days prior to the first dose of study medication
- Prior malignancy within 5 years prior to inclusion (exception: successfully treated basal cell carcinoma or in situ carcinoma)
- History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis
- Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding within 28 days prior to beginning study treatment, e.g
- Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product, e.g.
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 |
|---|---|---|
| Pazopanib as add-on to vinflunineAlso: Pazopanib is marketed as Votrient., Vinflunine is marketed as Javlor.Patients will receive vinflunine standard regimen (intravenous infusion every three weeks) as specified per drug label plus additional pazopanib as daily oral medication. Doses of pazopanib will be escalated in 200 mg/d steps during phase I up to a maximum of 800 mg/d. In Phase II the patients will be given pazopanib + vinflunine at maximum tolerated dose. | Drug | Pazopanib + Vinflunine |
Primary outcome
Phase I: Definition of the Maximum Tolerated Dose (MTD) of Pazopanib in combination with Vinflunine.
Time frame: 6 weeks (two cycles of vinflunine)
MTD ist defined as the dose level with dose-limiting toxicity occurring in maximum one out of six patients.
Phase II: Progression-free survival rate
Time frame: 3 months
Progression-free survival will be assessed by means of RECIST 1.1. methodology
1 secondary outcome
Phase I: Progression-free survival rate, Phase II: Safety profile, overall survival
Time frame: Six weeks after first administration of study drug.
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 10 Oct 2012.
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pazopanib as add-on to vinflunine in people with Advanced Urothelial Cancer of Bladder After Failure of Platinum-containing Therapy., run by Prof. Dr. Thomas Otto at 1 site in Germany.
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 38 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 10 Oct 2012. 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 Germany. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Phase I: Definition of the Maximum Tolerated Dose (MTD) of Pazopanib in combination with Vinflunine. (time frame: 6 weeks (two cycles of vinflunine)). The study lists 2 primary outcomes in all. 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 10 Oct 2012.