Adenocarcinoma of the BladderPhase 2NCT00407485
VEGF Trap in Treating Patients With Recurrent, Locally Advanced, or Metastatic Cancer of the Urothelium
A Phase 2 study testing ziv-aflibercept and pharmacological study in people with Adenocarcinoma of the Bladder and Distal Urethral Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase II trial is studying the side effects and how well VEGF Trap works in treating patients with recurrent, locally advanced, or metastatic cancer of the urothelium. VEGF Trap may stop the growth of tumor cells by blocking blood flow to the tumor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma of the Bladder, Distal Urethral Cancer, Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter
- What is being tested?
- ziv-aflibercept and pharmacological study
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2006to Apr 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histologically confirmed transitional cell carcinoma (TCC) of the urothelium
- Must have predominance of transitional histology, but foci of squamous and/or adenocarcinoma histology allowed
- Poorly differentiated transitional cell carcinoma allowed
- TCC of any of the following sites allowed:
- Bladder
- Renal pelvis
Show all 53Show fewer
- Ureter
- Urethra
- Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
- Locoregionally advanced or metastatic disease that is not amenable to curative surgery and/or radiotherapy
- Must have received 1 prior systemic chemotherapy regimen containing a platinum compound (e.g., cisplatin, carboplatin, or oxaliplatin) in the neoadjuvant, adjuvant, or metastatic setting
- No evidence of CNS disease, including primary brain tumor or brain metastases
- ECOG performance status 0-2
- Absolute neutrophil count >= 1,000/mm^3
- Platelet count >= 75,000/mm^3
- Bilirubin =< 1.5 times upper limit of normal (ULN)
- AST or ALT =< 2.5 times ULN
- Creatinine =< 2.5 times ULN OR creatinine clearance => 40 mL/min
- Urine protein: creatinine ratio =< 1 OR 24-hour urine protein < 500 mg
- INR =< 1.5 (unless on full-dose warfarin)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for >= 6 months after completion of study treatment
- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- No history of allergic reactions attributed to compounds of similar chemical or biological composition to other agents used in the study
- No serious or nonhealing wound, ulcer, or bone fracture
- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
- No significant traumatic injury within the past 28 days
- No clinically significant cardiovascular disease, including any of the following:
- Myocardial infarction, coronary artery bypass graft, or unstable angina pectoris within the past 6 months
- New York Heart Association class III or IV congestive heart failure
- Serious cardiac arrhythmia requiring medication
- Clinically significant peripheral vascular disease within the past 6 months
- Cerebrovascular accident within the past 6 months
- Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months
- Uncontrolled hypertension, defined as blood pressure (BP) > 150/100 mm Hg or systolic BP > 180 mm Hg (if diastolic BP < 90 mm Hg) within the past 3 months
- No evidence of bleeding diathesis or coagulopathy
- No uncontrolled intercurrent illness, including, but not limited to, any of the following:
- Ongoing or active infection
- Psychiatric illness or social situation that would preclude study compliance
- Recovered from prior therapy
- Prior biologic or targeted therapies allowed
- No more than 1 prior systemic chemotherapy regimen for metastatic disease
- No prior antiangiogenic therapy primarily targeting the vascular endothelial growth factor pathway
- At least 4 weeks since prior radiotherapy or systemic therapy (6 weeks for mitomycin C or nitrosoureas)
- More than 28 days since prior major surgery or open biopsy
- More than 7 days since prior core biopsy
- No concurrent major surgery
- Concurrent full-dose anticoagulants (e.g., warfarin) allowed provided all of the following criteria are met:
- In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or low molecular weight heparin
- No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
- No other concurrent investigational agents
- No concurrent combination antiretroviral therapy for HIV-positive patients
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study of VEGF Trap (NSC 724770) in Patients With Recurrent or Metastatic Transitional Carcinoma of the Urothelium
This phase II trial is studying the side effects and how well VEGF Trap works in treating patients with recurrent, locally advanced, or metastatic cancer of the urothelium. VEGF Trap may stop the growth of tumor cells by blocking blood flow to the tumor.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the response rate in patients with recurrent, locoregionally advanced, or metastatic transitional cell carcinoma of the urothelium treated with VEGF Trap.
II. Determine the time to progression in patients treated with this drug. III. Determine overall survival of patients treated with this drug. IV. Determine the tolerability and safety of this drug in these patients.
OUTLINE: This is a multicenter study.
Patients receive VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection periodically during study for pharmacokinetic/pharmacodynamic correlative studies.
After completion of study treatment, patients are followed periodically.
- Conditions
- Adenocarcinoma of the Bladder, Distal Urethral Cancer, Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter, Proximal Urethral Cancer, Recurrent Bladder Cancer, Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
- Being tested
- ziv-aflibercept, pharmacological study
- Medical subject headings
- Urinary Bladder Neoplasms, Urethral Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ziv-afliberceptBiological
Given IV
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (ziv-aflibercept) | Experimental | Patients receive 4 mg/kg VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. Receives: Biological: ziv-aflibercept; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Response Rate
Response rate (RR) and progression free survival (PFS) were assessed in a 2-stage accrual design (22+18). A maximum of 40 patients were to be accrued to rule out a null hypothesized RR of 4% and PFS of 3 months versus alternative of 15% RR and 5.4 months PFS (corresponding to 4 month PFS of 40% vs 60%) with α=0.12 and β=0.19. If no more than 1 objective response (no more than 4.5%), and no more than 10 instances of 4-month PFS (no more than 45%), were observed among the initial 22 patients, the study would be terminated early and declared negative. Tumor response was evaluated by CT or MRI using RECIST v1.0 criteria.
Responders were confirmed partial or complete responses to treatment.
Measured: From the start of the treatment until disease progression or recurrence, assessed up to 4 years
Progression-free Survival (PFS)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions PFS using the product-limit method of Kaplan and Meier.
Measured: From start of treatment to time of progression, assessed up to 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2006 (estimated)
- Study startNov 2006
- Primary completionApr 2010
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adenocarcinoma of the BladderStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Przemyslaw Twardowski, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00407485
- Sponsor's protocol ID
- NCI-2012-02840
- Other IDs
- NCI-2012-02840, PHII-76, 7533, N01CM62201, N01CM62209
- Status last verified
- Oct 2013
- First submitted
- 4 Dec 2006
- Last updated
- 20 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of VEGF Trap (NSC 724770) in Patients With Recurrent or Metastatic Transitional Carcinoma of the Urothelium
- ClinicalTrials.gov ID
- NCT00407485
- Acronym / sponsor ID
- NCI-2012-02840
- Conditions
- Adenocarcinoma of the Bladder, Distal Urethral Cancer, Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter, Proximal Urethral Cancer, Recurrent Bladder Cancer, Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Nov 2006
- Primary completion
- Apr 2010 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 5 Dec 2006 (estimated)
- Results
- Posted 3 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying the side effects and how well VEGF Trap works in treating patients with recurrent, locally advanced, or metastatic cancer of the urothelium. VEGF Trap may stop the growth of tumor cells by blocking blood flow to the tumor.
Detailed description
PRIMARY OBJECTIVES:
- Determine the response rate in patients with recurrent, locoregionally advanced, or metastatic transitional cell carcinoma of the urothelium treated with VEGF Trap.
II. Determine the time to progression in patients treated with this drug. III. Determine overall survival of patients treated with this drug. IV. Determine the tolerability and safety of this drug in these patients.
OUTLINE: This is a multicenter study.
Patients receive VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection periodically during study for pharmacokinetic/pharmacodynamic correlative studies.
After completion of study treatment, patients are followed periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ziv-aflibercept) | Experimental | Biological: ziv-aflibercept, Other: pharmacological studyPatients receive 4 mg/kg VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (53 listed)
- Histologically confirmed transitional cell carcinoma (TCC) of the urothelium
- TCC of any of the following sites allowed:
- Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
- Locoregionally advanced or metastatic disease that is not amenable to curative surgery and/or radiotherapy
- Must have received 1 prior systemic chemotherapy regimen containing a platinum compound (e.g., cisplatin, carboplatin, or oxaliplatin) in the neoadjuvant, adjuvant, or metastatic setting
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| ziv-afliberceptGiven IV | Biological | Treatment (ziv-aflibercept) |
| pharmacological studyCorrelative studies | Other | Treatment (ziv-aflibercept) |
Primary outcome
Tumor Response Rate
Time frame: From the start of the treatment until disease progression or recurrence, assessed up to 4 years
Response rate (RR) and progression free survival (PFS) were assessed in a 2-stage accrual design (22+18). A maximum of 40 patients were to be accrued to rule out a null hypothesized RR of 4% and PFS of 3 months versus alternative of 15% RR and 5.4 months PFS (corresponding to 4 month PFS of 40% vs 60%) with α=0.12 and β=0.19. If no more than 1 objective response (no more than 4.5%), and no more than 10 instances of 4-month PFS (no more than 45%), were observed among the initial 22 patients, the study would be terminated early and declared negative. Tumor response was evaluated by CT or MRI using RECIST v1.0 criteria. Responders were confirmed partial or complete responses to treatment.
Progression-free Survival (PFS)
Time frame: From start of treatment to time of progression, assessed up to 4 months
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions PFS using the product-limit method of Kaplan and Meier.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Przemyslaw Twardowski principal investigator
City of Hope Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ziv-aflibercept and pharmacological study in people with Adenocarcinoma of the Bladder and Distal Urethral Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
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 53 inclusion and 0 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 20 Oct 2014. 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 States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Tumor Response Rate (time frame: From the start of the treatment until disease progression or recurrence, assessed up to 4 years). 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 20 Oct 2014.