Urothelial CancerPhase 2NCT01700010
Trial of Lapatinib and Weekly Paclitaxel for Advanced Urothelial Cancer
A Phase 2 study testing Lapatinib and Paclitaxel in people with Urothelial Cancer and Bladder Cancer, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
This study will involve subjects who have advanced urothelial cancer who are platinum refractory (platinum based chemotherapies that are not effective in treating the cancer), and who are over-expressing EGFR and/or HER2, or do not over-express EGFR and HER2. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Cancer, Bladder Cancer
- What is being tested?
- Lapatinib and Paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2012to Jan 2019
- Phase
- Phase 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
- Male and female patients must be at least 18 years of age.
- Diagnosis of urothelial carcinoma that is locally advanced, recurrent or metastatic is required.
- Patients must have progressed on prior regimens (1-2 allowed) of systemic chemotherapy for any stage of urothelial carcinoma (including peri-operative chemotherapy alone in which case they must have progressed within 12 months of peri-operative chemotherapy), with one of the regimens including a platinum agent.
- Patients must have adequate tumor tissue (primary or metastatic tumor; fresh or archived) available for EGFR and HER2 expression analysis at baseline as determined by the study pathologist.
- EGFR and HER2 status by Immunohistochemistry of a potential patient's urothelial tumor must be determined at baseline before registration or therapy. A potential patient's eligibility will depend on his/her tumor's EGFR and HER2 category AND the available open slots in that category at that time.
- Patients must be able to care for themselves and must be up and about more than 50% of waking hours.
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- Patients must have measurable disease.
- Prior chemotherapy or radiation therapy must have been completed prior to registration (at least 4 weeks prior for chemotherapy and at least 2 weeks prior for radiation). Patients must have recovered from any reversible side effects and must not have had more than 25% of the bone marrow irradiated.
- Ability of the heart to pump blood must be adequate for this study. This will be determined by a screening test.
- Patients must have adequate organ and marrow function as determined by screening tests.
- All patients must be informed of the investigational nature of this study and must sign an informed consent document.
- Both men and women and members of all races and ethnic groups are eligible for this trial.
Who cannot join
- No prior use of anti-HER2 (including trastuzumab) or anti-EGFR (including erlotinib, gefitinib, cetuximab) therapy, paclitaxel, nanoparticle bound paclitaxel or docetaxel for any reason.
- Must not have history of or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease. Patients with known brain metastases would be excluded from this clinical trial.
- Known HIV positive patients may not participate.
- No malignancy for which systemic therapy, surgery or radiation is ongoing or anticipated within the next 3 months as assessed by the investigator.
- In situ carcinoma of any site including CIS of the urothelial tract [or] adequately treated basal cell or squamous cell skin cancer is allowed.
- Patients with history of non-metastatic prostate cancer who have a PSA <2 ng/mL with or without androgen deprivation therapy are eligible.
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- Patients with serious cardiac illness or medical conditions are excluded.
- Patients must not receive treatment on another therapeutic clinical trial. Supportive care trials and non-interventional trials, e.g. quality of life (QOL) trials are allowed..
- Herbal medications or supplements are not allowed.
- Female patients must be surgically sterile or be postmenopausal as per the investigator's discretion, or must agree to use effective contraception during the period of therapy. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to registration. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy.
- Must not have malabsorption syndrome, any disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, or unable to swallow oral medication.
- No history of allergic reactions to compounds of similar chemical or biologic composition to lapatinib.
- Use of strong CYP3A4 inhibitors or inducers is prohibited on study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Trial of Lapatinib and Weekly Paclitaxel for Advanced Platinum Refractory Urothelial Cancer
This study will involve subjects who have advanced urothelial cancer who are platinum refractory (platinum based chemotherapies that are not effective in treating the cancer), and who are over-expressing EGFR and/or HER2, or do not over-express EGFR and HER2. Genetic expression is a process that takes inherited information in genes (like DNA sequence), and from that information makes a specific functional product (sometimes called a gene product) such as RNA (ribonucleic acid) or protein. Normal tissue cells have a particular genetic expression, which changes when they turn into cancer. EGFR and HER2 are involved in the process by which normal cells are transformed into cancer cells.
The main purpose of the study is to look at the proportion of subjects, who over-express EGFR and/or HER2, who do not progress (cancer gets worse) after 16 weeks of study treatment with daily lapatinib and weekly paclitaxel. The study will also look at the safety and effectiveness of this therapy in all subjects.
Another part of this study will look at blood and tissue samples. Blood samples will be collected to see how many cells express EGFR and HER2 before study treatment and at the time the cancer gets worse. Tumor tissue will be analyzed to look at the expression of certain genes in advanced urothelial cancer. Some gene expression tests can reveal how cancer cells are different from normal cells and the results might lead to more accurate diagnosis and treatment.
Read the detailed description
Bladder cancer caused 14,680 deaths in 2010 in the US. In advanced bladder cancer, MVAC (methotrexate, vinblastine, adriamycin and cisplatin) and GC (gemcitabine, cisplatin) combination chemotherapy demonstrate comparable efficacy with response rates of 45%- 50%. Despite the reasonable initial response to platinum based chemotherapy, median time to progression on first line therapy is only 7 months and median survival approximately 15 months. There is no standard second line therapy after platinum based chemotherapy in the US and no survival benefit has been noted with any agent. Median progression free survival (PFS) is around 2 months in platinum refractory urothelial cancer (PRUC) and overall survival (OS) is 6 - 8 months with single agent second line therapy. Combination chemotherapy does not prolong overall survival. Given the dire prognosis in PRUC and the lack of efficacy of conventional chemotherapy, preclinical investigations and clinical research have focused on identification of novel molecular targets.
Lapatnib is approved by the FDA for the treatment of breast cancer. Paclitaxel is approved by the FDA for the treatment of sarcoma, breast and lung cancers. Lapatinib and paclitaxel are not approved for advanced urothelial cancer; however, the FDA allows the use of these drugs in this study for research purposes.
- Conditions
- Urothelial Cancer, Bladder Cancer
- Being tested
- Lapatinib and Paclitaxel
- Keywords
- Urothelial, Bladder, Cancer
- Medical subject headings
- Urinary Bladder Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lapatinib and PaclitaxelDrug
Lapatinib comes in tablet form and is taken by mouth at a dose of 1,000 mg every day. Paclitaxel will be given through the vein (IV) at a dose of 80 mg/m2 on days 1, 8, and 15 at each 28 day cycle. If cancer does not progress and study treatment can be tolerated after 6 cycles of paclitaxel and lapatinib, paclitaxel will be stopped and lapatinib will continue until disease progression, side effects cannot be tolerated, participant is removed from or withdraws from study, or for other reasons.
Subjects with locally advanced disease who respond to treatment and are felt to be appropriate for local therapy may proceed to receive local therapy as deemed appropriate by the managing physician after a minimum of 6 cycles or upon achieving complete remission followed by an additional 2 cycles. Subjects who proceed to receive local therapy will be removed from protocol therapy. Subjects who elect not to receive or are not candidates for local therapy may continue treatment on protocol.
| Study group | Role | What they receive |
|---|---|---|
| Lapatinib and Paclitaxel | Experimental | Lapatinib comes in tablet form and is taken by mouth at a dose of 1,000 mg every day. Paclitaxel will be given through the vein (IV) at a dose of 80 mg/m2 on days 1, 8, and 15 at each 28 day cycle. If cancer does not progress and study treatment can be tolerated after 6 cycles of paclitaxel and lapatinib, paclitaxel will be stopped and lapatinib will continue until disease progression, side effects cannot be tolerated, participant is removed from or withdraws from study, or for other reasons.
Subjects with locally advanced disease who respond to treatment and are felt to be appropriate for local therapy may proceed to receive local therapy as deemed appropriate by the managing physician after a minimum of 6 cycles or upon achieving complete remission followed by an additional 2 cycles. Subjects who proceed to receive local therapy will be removed from protocol therapy. Subjects who elect not to receive or are not candidates for local therapy may continue treatment on protocol. Receives: Drug: Lapatinib and Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free
The proportion of patients with platinum refractory advanced urothelial cancer over-expressing EGFR and/or HER2 who do not progress after 16 weeks of therapy with lapatinib and weekly paclitaxel.
Measured: 16 weeks after participant study therapy
Secondary outcomes (4)
Number of participants with adverse events
Safety of combination lapatinib and weekly paclitaxel.
Measured: 5.5 years
The overall response proportion
The overall response proportion (complete response + partial response) in patients with platinum refractory urothelial cancer treated with lapatinib and weekly paclitaxel whose tumors over-express EGFR and/or HER2; whose tumors over-express only EGFR or only HER2; and whose tumors over-express neither EGFR nor HER2.
Measured: Up to 12 months after the last subject comes off study treatment.
Median progression free survival
Median progression free survival in patients with platinum refractory urothelial cancer treated with lapatinib and weekly paclitaxel whose tumors over-express EGFR and/or HER2; whose tumors over-express only EGFR or only HER2; and whose tumors over-express neither EGFR nor HER2.
Measured: Up to 12 months after the last subject comes off study treatment.
Overall survival
The overall survival in patients with platinum refractory urothelial cancer treated with lapatinib and weekly paclitaxel whose tumors over-express EGFR and/or HER2; whose tumors over-express only EGFR or only HER2; and whose tumors over-express neither EGFR nor HER2.
Measured: Up to 12 months after the last subject comes off study treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2012 (estimated)
- Study startNov 2012
- Primary completionJan 2017 (estimated)
- Study completionJan 2019 (estimated)
Why it stopped: Funding issues.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial CancerStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Ajjai S. Alva, M.D., Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01700010
- Sponsor's protocol ID
- UMCC 2012.045
- Other IDs
- HUM00062889
- Status last verified
- Jan 2013
- First submitted
- 2 Oct 2012
- Last updated
- 17 Jan 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Lapatinib and Weekly Paclitaxel for Advanced Platinum Refractory Urothelial Cancer
- ClinicalTrials.gov ID
- NCT01700010
- Acronym / sponsor ID
- UMCC 2012.045
- Conditions
- Urothelial Cancer, Bladder Cancer
- Keywords
- Urothelial, Bladder, Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding issues.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Nov 2012
- Primary completion
- Jan 2017 (estimated)
- Study completion
- Jan 2019 (estimated)
- First posted
- 4 Oct 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.
This study will involve subjects who have advanced urothelial cancer who are platinum refractory (platinum based chemotherapies that are not effective in treating the cancer), and who are over-expressing EGFR and/or HER2, or do not over-express EGFR and HER2. Genetic expression is a process that takes inherited information in genes (like DNA sequence), and from that information makes a specific functional product (sometimes called a gene product) such as RNA (ribonucleic acid) or protein. Normal tissue cells have a particular genetic expression, which changes when they turn into cancer. EGFR and HER2 are involved in the process by which normal cells are transformed into cancer cells.
The main purpose of the study is to look at the proportion of subjects, who over-express EGFR and/or HER2, who do not progress (cancer gets worse) after 16 weeks of study treatment with daily lapatinib and weekly paclitaxel. The study will also look at the safety and effectiveness of this therapy in all subjects.
Another part of this study will look at blood and tissue samples. Blood samples will be collected to see how many cells express EGFR and HER2 before study treatment and at the time the cancer gets worse. Tumor tissue will be analyzed to look at the expression of certain genes in advanced urothelial cancer. Some gene expression tests can reveal how cancer cells are different from normal cells and the results might lead to more accurate diagnosis and treatment.
Detailed description
Bladder cancer caused 14,680 deaths in 2010 in the US. In advanced bladder cancer, MVAC (methotrexate, vinblastine, adriamycin and cisplatin) and GC (gemcitabine, cisplatin) combination chemotherapy demonstrate comparable efficacy with response rates of 45%- 50%. Despite the reasonable initial response to platinum based chemotherapy, median time to progression on first line therapy is only 7 months and median survival approximately 15 months. There is no standard second line therapy after platinum based chemotherapy in the US and no survival benefit has been noted with any agent. Median progression free survival (PFS) is around 2 months in platinum refractory urothelial cancer (PRUC) and overall survival (OS) is 6 - 8 months with single agent second line therapy. Combination chemotherapy does not prolong overall survival. Given the dire prognosis in PRUC and the lack of efficacy of conventional chemotherapy, preclinical investigations and clinical research have focused on identification of novel molecular targets.
Lapatnib is approved by the FDA for the treatment of breast cancer. Paclitaxel is approved by the FDA for the treatment of sarcoma, breast and lung cancers. Lapatinib and paclitaxel are not approved for advanced urothelial cancer; however, the FDA allows the use of these drugs in this study for research purposes.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lapatinib and Paclitaxel | Experimental | Drug: Lapatinib and PaclitaxelLapatinib comes in tablet form and is taken by mouth at a dose of 1,000 mg every day. Paclitaxel will be given through the vein (IV) at a dose of 80 mg/m2 on days 1, 8, and 15 at each 28 day cycle. If cancer does not progress and study treatment can be tolerated after 6 cycles of paclitaxel and lapatinib, paclitaxel will be stopped and lapatinib will continue until disease progression, side effects cannot be tolerated, participant is removed from or withdraws from study, or for other reasons. Subjects with locally advanced disease who respond to treatment and are felt to be appropriate for local therapy may proceed to receive local therapy as deemed appropriate by the managing physician after a minimum of 6 cycles or upon achieving complete remission followed by an additional 2 cycles. Subjects who proceed to receive local therapy will be removed from protocol therapy. Subjects who elect not to receive or are not candidates for local therapy may continue treatment on protocol. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Male and female patients must be at least 18 years of age.
- Diagnosis of urothelial carcinoma that is locally advanced, recurrent or metastatic is required.
- Patients must have progressed on prior regimens (1-2 allowed) of systemic chemotherapy for any stage of urothelial carcinoma (including peri-operative chemotherapy alone in which case they must have progressed within 12 months of peri-operative chemotherapy), with one of the regimens including a platinum agent.
- Patients must have adequate tumor tissue (primary or metastatic tumor; fresh or archived) available for EGFR and HER2 expression analysis at baseline as determined by the study pathologist.
- EGFR and HER2 status by Immunohistochemistry of a potential patient's urothelial tumor must be determined at baseline before registration or therapy. A potential patient's eligibility will depend on his/her tumor's EGFR and HER2 category AND the available open slots in that category at that time.
Key exclusion criteria (13 listed)
- No prior use of anti-HER2 (including trastuzumab) or anti-EGFR (including erlotinib, gefitinib, cetuximab) therapy, paclitaxel, nanoparticle bound paclitaxel or docetaxel for any reason.
- Must not have history of or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease. Patients with known brain metastases would be excluded from this clinical trial.
- Known HIV positive patients may not participate.
- No malignancy for which systemic therapy, surgery or radiation is ongoing or anticipated within the next 3 months as assessed by the investigator.
- Patients with serious cardiac illness or medical conditions are excluded.
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 |
|---|---|---|
| Lapatinib and PaclitaxelLapatinib comes in tablet form and is taken by mouth at a dose of 1,000 mg every day. Paclitaxel will be given through the vein (IV) at a dose of 80 mg/m2 on days 1, 8, and 15 at each 28 day cycle. If cancer does not progress and study treatment can be tolerated after 6 cycles of paclitaxel and lapatinib, paclitaxel will be stopped and lapatinib will continue until disease progression, side effects cannot be tolerated, participant is removed from or withdraws from study, or for other reasons. Subjects with locally advanced disease who respond to treatment and are felt to be appropriate for local therapy may proceed to receive local therapy as deemed appropriate by the managing physician after a minimum of 6 cycles or upon achieving complete remission followed by an additional 2 cycles. Subjects who proceed to receive local therapy will be removed from protocol therapy. Subjects who elect not to receive or are not candidates for local therapy may continue treatment on protocol. | Drug | Lapatinib and Paclitaxel |
Primary outcome
Progression free
Time frame: 16 weeks after participant study therapy
The proportion of patients with platinum refractory advanced urothelial cancer over-expressing EGFR and/or HER2 who do not progress after 16 weeks of therapy with lapatinib and weekly paclitaxel.
4 secondary outcomes
Number of participants with adverse events
Time frame: 5.5 years
The overall response proportion
Time frame: Up to 12 months after the last subject comes off study treatment.
Median progression free survival
Time frame: Up to 12 months after the last subject comes off study treatment.
Overall survival
Time frame: Up to 12 months after the last subject comes off study treatment.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2013.
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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.
Ajjai S. Alva, M.D. principal investigator
University of Michigan
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 Lapatinib and Paclitaxel in people with Urothelial Cancer and Bladder Cancer, run by University of Michigan Rogel Cancer Center 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 12 inclusion and 13 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: withdrawn, as of the sponsor's last update on 17 Jan 2013. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Progression free (time frame: 16 weeks after participant study therapy). 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 17 Jan 2013.