Urothelial CancerPhase 2NCT01663285
Clinical Trial Of Neoadjuvant Chemotherapy (NAC)In Upper Tract Urothelial Carcinoma (UTUC)
A Phase 2 study testing Neoadjuvant Cisplatin and Gemcitabine in people with Urothelial Cancer and Bladder Cancer, run by University of Michigan Rogel Cancer Center at 3 sites in United States.
Trial summary
The main purpose of this study is to look at the cancer-free survival at two years of subjects with high risk upper tract urothelial cancer when treated with the combination of two chemotherapy drugs called Gemcitabine and Cisplatin followed by surgery to remove the kidney, all or part of the ureter (ureters are tubes… 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?
- Neoadjuvant Cisplatin and Gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2012to Jan 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
- Patients must have HIGH GRADE upper tract urothelial carcinoma
- Patients must be considered to be a candidate for surgery with curative intent (nephroureterectomy or distal ureterectomy) with lymph node dissection by the treating urologist at baseline within 42 days prior to registration.
- Patients must be able to care for themselves and must be up and about more than 50% of waking hours
- All patients must be evaluated by a medical oncologist at baseline within 42 days prior to registration. Patients must be considered to be a candidate for cisplatin-based neoadjuvant chemotherapy by a medical oncologist at baseline and must have adequate kidney function and any pre-existing peripheral neuropathy must be moderate to mild.
- Prior uro-oncologic history:
- History of or active non-invasive carcinoma or carcinoma in situ of the bladder or upper tract is allowed.
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- Patients may have received prior intravesical chemotherapy or immunotherapy such as BCG.
- Prior neoadjuvant chemotherapy for bladder cancer or invasive contralateral upper tract cancer is allowed.
- Prior adjuvant chemotherapy for bladder cancer or invasive contralateral upper tract cancer is allowed but must have been completed ≥2 years prior to study registration.
- Patients must have adequate organ and bone marrow function as determined by screening tests
- Patients must have recovered from any reversible toxicities of prior procedure or surgery
- Patients must be 18 years or older on date of registration
- All patients must be informed of the investigational nature of this study and must sign an informed consent document
Who cannot join
- Patients must have no evidence of regional lymphadenopathy or distant metastasis on imaging.
- No history of invasive or node positive or metastatic bladder cancer or invasive contralateral upper tract cancer within 2 years prior to registration.
- Patients with one kidney are not eligible
- Patients may not be enrolled in another interventional clinical trial at the time of registration.
- No prior non-urothelial malignancy is allowed, except for cancer from which the patient has been disease free for at least 1 year at the discretion of the treating oncologist. History of adequately treated (at the discretion of the treating oncologist) basal cell or squamous cell skin cancer or in situ cervical cancers is allowed.
- Pregnant or lactating women are not eligible. Women/men of reproductive potential must agree to use an effective contraceptive method. Women with reproductive potential must have a negative pregnancy test within 14 days prior to registration.
- Patients must not have any other medical condition(s) that make(s) their participation in the study unadvisable in the opinion of the treating oncologist.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Michigan
Ann Arbor, Michigan, 48109
Oregon Health Sciences University
Portland, Oregon, 97239
University of Rochester
Rochester, New York, 14642
About this study
Official title: Phase II Clinical Trial Of Neoadjuvant Chemotherapy (NAC)In Upper Tract Urothelial Carcinoma (UTUC)
The main purpose of this study is to look at the cancer-free survival at two years of subjects with high risk upper tract urothelial cancer when treated with the combination of two chemotherapy drugs called Gemcitabine and Cisplatin followed by surgery to remove the kidney, all or part of the ureter (ureters are tubes made of smooth muscle fibers that propel urine from the kidneys to the urinary bladder), and a cuff of bladder where the ureter drains into the bladder. Other purposes of the study include looking at the safety of Gemcitabine and Cisplatin before surgery for this type of cancer, time to recurrence of cancer, and overall survival.
Exploratory integrative tumor sequencing:
The purpose of this part of the study is to test deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) in various types of samples (tissue and blood) to detect different types of cancer genetic changes in upper tract urothelial cancer (UTUC) to help develop future studies in UTUC. DNA and RNA contain key instructions for cell function and help determine the characteristics of each individual such as hair, eye, and skin color, height, susceptibility to diseases, and other characteristics.
Read the detailed description
In recent years, the combination of gemcitabine and cisplatin given every 21 days (gemcitabine on days 1 and 8 only) has been used in trials and routine clinical practice. Additionally, surgery, primarily radical nephroureterectomy (RNU) with bladder cuff removal, is the current standard treatment for invasive upper tract urothelial carcinoma.
Upper tract urothelial cancer (UTUC) or urothelial cancer arising in the pelvicalyceal or ureteral locations is a lethal cancer accounting for 5% of all urothelial cancers. In urothelial cancer of the bladder, randomized clinical trials and meta-analyses have shown a survival advantage with neoadjuvant cisplatin-based chemotherapy. It is conceivable that a similar approach may benefit patients with UTUC.
Both Gemcitabine and Cisplatin are approved by the FDA. Cisplatin is approved for use in urothelial cancer. Gemcitabine is FDA approved to be used alone or with other drugs to treat breast, non-small lung, ovarian, and pancreatic cancers. Gemcitabine is not approved by the FDA for urothelial cancer, but it is typically used together with Cisplatin in trials and routine clinical practice for treating urothelial cancer.
Exploratory integrative tumor sequencing:
The biology of UTUC is poorly understood due to the relative rarity of the disease and the lack of comprehensive genomic and translational studies. This trial offers a rare opportunity to apply high-throughput sequencing techniques in UTUC to detect several classes of cancer mutations including structural rearrangements, copy number alterations, point mutations, and gene expression alterations. This research could help to develop future studies in UTUC to help researchers understand more about UTUC and how to treat it. Additionally, we may identify a potentially important result from DNA samples from subjects that could possibly help manage their cancer better by pursing a different cancer therapy rather than the study therapy.
- Conditions
- Urothelial Cancer, Bladder Cancer
- Being tested
- Neoadjuvant Cisplatin and Gemcitabine
- 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.
Neoadjuvant Cisplatin and GemcitabineDrug
Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant Gemcitabine and Cisplatin | Experimental | Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy. Receives: Drug: Neoadjuvant Cisplatin and Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence-free Survival Time
The 2-year recurrence-free survival (RFS) time for patients treated with neoadjuvant cisplatin and gemcitabine chemotherapy followed by surgery in high risk upper tract urothelial carcinoma.
Measured: 2 years after participant surgery
Secondary outcomes (2)
Number of Patients With Pathologic T0/Tis/Ta N0.
The proportion of patients with pathologic T0/Tis/Ta N0.
Measured: 51 months
Number of Participants With Adverse Events
The safety of neoadjuvant chemotherapy.
Measured: 9 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2012 (estimated)
- Study startSep 2012
- Primary completionJan 2014
- Study completionJan 2014
Why it stopped: Low study participant enrollment.
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 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
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ajjai S. Alva, M.D., Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01663285
- Sponsor's protocol ID
- UMCC 2012.038
- Other IDs
- HUM00062285
- Status last verified
- Nov 2015
- First submitted
- 24 Jul 2012
- Last updated
- 3 Dec 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical Trial Of Neoadjuvant Chemotherapy (NAC)In Upper Tract Urothelial Carcinoma (UTUC)
- ClinicalTrials.gov ID
- NCT01663285
- Acronym / sponsor ID
- UMCC 2012.038
- Conditions
- Urothelial Cancer, Bladder Cancer
- Keywords
- Urothelial, Bladder, Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low study participant enrollment.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 13 Aug 2012 (estimated)
- Results
- Posted 18 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to look at the cancer-free survival at two years of subjects with high risk upper tract urothelial cancer when treated with the combination of two chemotherapy drugs called Gemcitabine and Cisplatin followed by surgery to remove the kidney, all or part of the ureter (ureters are tubes made of smooth muscle fibers that propel urine from the kidneys to the urinary bladder), and a cuff of bladder where the ureter drains into the bladder. Other purposes of the study include looking at the safety of Gemcitabine and Cisplatin before surgery for this type of cancer, time to recurrence of cancer, and overall survival.
Exploratory integrative tumor sequencing:
The purpose of this part of the study is to test deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) in various types of samples (tissue and blood) to detect different types of cancer genetic changes in upper tract urothelial cancer (UTUC) to help develop future studies in UTUC. DNA and RNA contain key instructions for cell function and help determine the characteristics of each individual such as hair, eye, and skin color, height, susceptibility to diseases, and other characteristics.
Detailed description
In recent years, the combination of gemcitabine and cisplatin given every 21 days (gemcitabine on days 1 and 8 only) has been used in trials and routine clinical practice. Additionally, surgery, primarily radical nephroureterectomy (RNU) with bladder cuff removal, is the current standard treatment for invasive upper tract urothelial carcinoma.
Upper tract urothelial cancer (UTUC) or urothelial cancer arising in the pelvicalyceal or ureteral locations is a lethal cancer accounting for 5% of all urothelial cancers. In urothelial cancer of the bladder, randomized clinical trials and meta-analyses have shown a survival advantage with neoadjuvant cisplatin-based chemotherapy. It is conceivable that a similar approach may benefit patients with UTUC.
Both Gemcitabine and Cisplatin are approved by the FDA. Cisplatin is approved for use in urothelial cancer. Gemcitabine is FDA approved to be used alone or with other drugs to treat breast, non-small lung, ovarian, and pancreatic cancers. Gemcitabine is not approved by the FDA for urothelial cancer, but it is typically used together with Cisplatin in trials and routine clinical practice for treating urothelial cancer.
Exploratory integrative tumor sequencing:
The biology of UTUC is poorly understood due to the relative rarity of the disease and the lack of comprehensive genomic and translational studies. This trial offers a rare opportunity to apply high-throughput sequencing techniques in UTUC to detect several classes of cancer mutations including structural rearrangements, copy number alterations, point mutations, and gene expression alterations. This research could help to develop future studies in UTUC to help researchers understand more about UTUC and how to treat it. Additionally, we may identify a potentially important result from DNA samples from subjects that could possibly help manage their cancer better by pursing a different cancer therapy rather than the study therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant Gemcitabine and Cisplatin | Experimental | Drug: Neoadjuvant Cisplatin and GemcitabineCisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must have HIGH GRADE upper tract urothelial carcinoma
- Patients must be considered to be a candidate for surgery with curative intent (nephroureterectomy or distal ureterectomy) with lymph node dissection by the treating urologist at baseline within 42 days prior to registration.
- Patients must be able to care for themselves and must be up and about more than 50% of waking hours
- All patients must be evaluated by a medical oncologist at baseline within 42 days prior to registration. Patients must be considered to be a candidate for cisplatin-based neoadjuvant chemotherapy by a medical oncologist at baseline and must have adequate kidney function and any pre-existing peripheral neuropathy must be moderate to mild.
- Prior uro-oncologic history:
Key exclusion criteria (7 listed)
- Patients must have no evidence of regional lymphadenopathy or distant metastasis on imaging.
- No history of invasive or node positive or metastatic bladder cancer or invasive contralateral upper tract cancer within 2 years prior to registration.
- Patients with one kidney are not eligible
- Patients may not be enrolled in another interventional clinical trial at the time of registration.
- No prior non-urothelial malignancy is allowed, except for cancer from which the patient has been disease free for at least 1 year at the discretion of the treating oncologist. History of adequately treated (at the discretion of the treating oncologist) basal cell or squamous cell skin cancer or in situ cervical cancers is allowed.
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 |
|---|---|---|
| Neoadjuvant Cisplatin and GemcitabineCisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy. | Drug | Neoadjuvant Gemcitabine and Cisplatin |
Primary outcome
Recurrence-free Survival Time
Time frame: 2 years after participant surgery
The 2-year recurrence-free survival (RFS) time for patients treated with neoadjuvant cisplatin and gemcitabine chemotherapy followed by surgery in high risk upper tract urothelial carcinoma.
2 secondary outcomes
Number of Patients With Pathologic T0/Tis/Ta N0.
Time frame: 51 months
Number of Participants With Adverse Events
Time frame: 9 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2015.
- 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.
Ajjai S. Alva, M.D. principal investigator
University of Michigan
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neoadjuvant Cisplatin and Gemcitabine in people with Urothelial Cancer and Bladder Cancer, run by University of Michigan Rogel Cancer Center at 3 sites 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 13 inclusion and 7 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: stopped early, as of the sponsor's last update on 3 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 18 Sep 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?
Recurrence-free Survival Time (time frame: 2 years after participant surgery). 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 3 Dec 2015.