Anterior Urethral CancerPhase 2NCT01639521
Gemcitabine Hydrochloride and Cisplatin or High-Dose Methotrexate, Vinblastine, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Urothelial Cancer
A Phase 2 study testing cisplatin, gemcitabine hydrochloride and methotrexate in people with Anterior Urethral Cancer and Localized Transitional Cell Cancer of the Renal Pelvis and Ureter, run by University of Southern California.
Trial summary
This study is about two chemotherapy study drug combinations (regimens) that are used for urothelial (bladder or upper urinary tract) cancer. Both study drug regimens, gemcitabine (gemcitabine hydrochloride) plus cisplatin, and high-dose-intensity MVAC (methotrexate, vinblastine, doxorubicin plus cisplatin), are… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anterior Urethral Cancer, Localized Transitional Cell Cancer of the Renal Pelvis and Ureter, Posterior Urethral Cancer
- What is being tested?
- cisplatin, gemcitabine hydrochloride and methotrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- May 2013to May 2013
- 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
- Histologically confirmed high-grade urothelial carcinoma, stage T3bN0, T4N0 or any T stage with lymph node involvement, completely resected; including upper tract urothelial carcinoma
- The dominant histology must be transitional cell or urothelial but foci of other histologies less than 20 percent of the total tumor volume are permitted
- Absence of metastatic disease on radiographic imaging
- Patients must be enrolled and able to start treatment within 90 days of radical cystectomy or radical nephrectomy
- Creatinine less than institutional upper limit of normal (ULN) or clearance greater or equal to 50 mL/min (may be calculated by Cockcroft-Gault formula or measured from 24-hour urine collection)
- Serum total bilirubin less or equal to 1.5 x ULN (except for patients with Gilbert's)
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- Alkaline phosphatase less or equal to 2.5 x ULN
- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) less or equal to 2.5 x ULN
- White blood cells (WBC) greater or equal to 3000
- Absolute neutrophil count (ANC) greater or equal to 1500
- Hemoglobin (Hb) greater or equal to 9
- Platelets greater or equal to 100,000
- Normal left ventricular ejection fraction, by echocardiogram or multi gated acquisition scan (MUGA)
- Patients must be recovered from surgery
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Willing and able to provide informed consent
- Willingness to use barrier contraception during study period
Who cannot join
- The presence of significant pleural effusion or ascites
- Prior systemic chemotherapy for urothelial carcinoma including neoadjuvant chemotherapy (prior intravesical therapy is permitted)
- History of malignancy within preceding 5 years, aside from non-melanoma skin cancer or previously treated or incidentally detected prostate cancer with undetectable PSA (after radical cystectomy or prostate cancer therapy)
- Peripheral neuropathy greater than grade 1
- The presence of active heart disease such as congestive heart failure or unstable angina
About this study
Official title: Randomized Phase II Trial Of Adjuvant Chemotherapy For Urothelial Carcinoma Comparing GC To Dose-Dense MVAC
This study is about two chemotherapy study drug combinations (regimens) that are used for urothelial (bladder or upper urinary tract) cancer. Both study drug regimens, gemcitabine (gemcitabine hydrochloride) plus cisplatin, and high-dose-intensity MVAC (methotrexate, vinblastine, doxorubicin plus cisplatin), are standard chemotherapy regimens. Both regimens are used to treat people with urothelial cancer that has spread to other organs. Both study drug regimens have been proven to be effective in lowering the risk of the cancer coming back, but it is not known which regimen is the best. This study hopes to learn whether there is a difference in the effectiveness and side effects of these two study drug regimens when they are given to people who have had their urothelial cancer completely removed.
Read the detailed description
PRIMARY OBJECTIVES
To estimate the difference in the rate of unacceptable toxicity for dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine and cisplatin (GC) in the adjuvant treatment of urothelial cancer.
SECONDARY OBJECTIVES
To compare rates of disease recurrence at 3 years between dose-dense MVAC and GC.
To determine whether molecular markers excision repair cross-complementing-1 (ERCC-1) ribonucleoside-diphosphate reductase M-1 (RRM-1), breast cancer 1 (BRCA1) topoisomerase 2-alpha (Top2A) and protein 53 (p53) can predict those patients more likely to benefit from chemotherapy.
To investigate the potential utility of cytidine deaminase (CDA), ERCC-1, xeroderma pigmentosum group D (XPD), glutathione S-transferase P-1 (GSTP-1) and glutathione S-transferase M-1 (GSTM-1) as molecular markers which predict occurrence of significant toxicity during adjuvant chemotherapy for urothelial cancer.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive cisplatin intravenously (IV) on day 1 and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive methotrexate IV on day 1, vinblastine IV, doxorubicin hydrochloride IV, cisplatin IV on day 2 and pegfilgrastim subcutaneously (SC) on day 3. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 3 years.
- Conditions
- Anterior Urethral Cancer, Localized Transitional Cell Cancer of the Renal Pelvis and Ureter, Posterior Urethral Cancer, Recurrent Bladder Cancer, Recurrent Urethral Cancer, Regional Transitional Cell Cancer of the Renal Pelvis and Ureter
- Being tested
- cisplatin, gemcitabine hydrochloride, methotrexate, vinblastine, doxorubicin hydrochloride
- Medical subject headings
- Urinary Bladder Neoplasms, Urethral Neoplasms, Ureteral Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cisplatinDrug
Also called CACP, CDDP, CPDD, DDP
Given IV
Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Given IV
methotrexateDrug
Also called amethopterin, Folex, methylaminopterin, Mexate
Given IV
vinblastineDrug
Also called Velban, Velsar, VLB
Given IV
Also called ADM, ADR, Adria, Adriamycin PFS
Given IV
pegfilgrastimBiological
Also called Filgrastim SD-01, GCSF-SD01, Neulasta, SD-01 sustained duration G-CSF
Given SC
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm A (gemcitabine hydrochloride, cisplatin) | Experimental | Patients receive cisplatin IV on day 1 and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: cisplatin; Drug: gemcitabine hydrochloride; Other: laboratory biomarker analysis |
| Arm B (MVAC) | Experimental | Patients receive methotrexate IV on day 1 and vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV on day 2. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: cisplatin; Drug: methotrexate; Drug: vinblastine; Drug: doxorubicin hydrochloride; Biological: pegfilgrastim; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of unacceptable toxicity graded according to Common Terminology Criteria (CTC) v4.0
80% confidence intervals (CI) will be constructed; for unacceptable toxicity, the confidence interval will be one-sided.
Measured: Assessed up to 3 years
Secondary outcomes (1)
Disease-free survival
Measured: From radical cystectomy to the time cancer recurrence is detected by clinical findings or during surveillance imaging, at 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2012 (estimated)
- Study startMay 2013
- Primary completionMay 2013
- Study completionMay 2013
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anterior Urethral CancerStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Tanya Dorff, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01639521
- Sponsor's protocol ID
- 4B-10-5
- Other IDs
- NCI-2012-00961
- Status last verified
- Jan 2014
- First submitted
- 10 Jul 2012
- Last updated
- 29 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Trial Of Adjuvant Chemotherapy For Urothelial Carcinoma Comparing GC To Dose-Dense MVAC
- ClinicalTrials.gov ID
- NCT01639521
- Acronym / sponsor ID
- 4B-10-5
- Conditions
- Anterior Urethral Cancer, Localized Transitional Cell Cancer of the Renal Pelvis and Ureter, Posterior Urethral Cancer, Recurrent Bladder Cancer, Recurrent Urethral Cancer, Regional Transitional Cell Cancer of the Renal Pelvis and Ureter
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2013
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 12 Jul 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 is about two chemotherapy study drug combinations (regimens) that are used for urothelial (bladder or upper urinary tract) cancer. Both study drug regimens, gemcitabine (gemcitabine hydrochloride) plus cisplatin, and high-dose-intensity MVAC (methotrexate, vinblastine, doxorubicin plus cisplatin), are standard chemotherapy regimens. Both regimens are used to treat people with urothelial cancer that has spread to other organs. Both study drug regimens have been proven to be effective in lowering the risk of the cancer coming back, but it is not known which regimen is the best. This study hopes to learn whether there is a difference in the effectiveness and side effects of these two study drug regimens when they are given to people who have had their urothelial cancer completely removed.
Detailed description
PRIMARY OBJECTIVES
To estimate the difference in the rate of unacceptable toxicity for dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine and cisplatin (GC) in the adjuvant treatment of urothelial cancer.
SECONDARY OBJECTIVES
To compare rates of disease recurrence at 3 years between dose-dense MVAC and GC.
To determine whether molecular markers excision repair cross-complementing-1 (ERCC-1) ribonucleoside-diphosphate reductase M-1 (RRM-1), breast cancer 1 (BRCA1) topoisomerase 2-alpha (Top2A) and protein 53 (p53) can predict those patients more likely to benefit from chemotherapy.
To investigate the potential utility of cytidine deaminase (CDA), ERCC-1, xeroderma pigmentosum group D (XPD), glutathione S-transferase P-1 (GSTP-1) and glutathione S-transferase M-1 (GSTM-1) as molecular markers which predict occurrence of significant toxicity during adjuvant chemotherapy for urothelial cancer.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive cisplatin intravenously (IV) on day 1 and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive methotrexate IV on day 1, vinblastine IV, doxorubicin hydrochloride IV, cisplatin IV on day 2 and pegfilgrastim subcutaneously (SC) on day 3. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (gemcitabine hydrochloride, cisplatin) | Experimental | Drug: cisplatin, Drug: gemcitabine hydrochloride, Other: laboratory biomarker analysisPatients receive cisplatin IV on day 1 and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. |
| Arm B (MVAC) | Experimental | Drug: cisplatin, Drug: methotrexate, Drug: vinblastine, Drug: doxorubicin hydrochloride, Biological: pegfilgrastim, Other: laboratory biomarker analysisPatients receive methotrexate IV on day 1 and vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV on day 2. Treatment repeats every 14 days for 4 courses 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 (17 listed)
- Histologically confirmed high-grade urothelial carcinoma, stage T3bN0, T4N0 or any T stage with lymph node involvement, completely resected; including upper tract urothelial carcinoma
- The dominant histology must be transitional cell or urothelial but foci of other histologies less than 20 percent of the total tumor volume are permitted
- Absence of metastatic disease on radiographic imaging
- Patients must be enrolled and able to start treatment within 90 days of radical cystectomy or radical nephrectomy
- Creatinine less than institutional upper limit of normal (ULN) or clearance greater or equal to 50 mL/min (may be calculated by Cockcroft-Gault formula or measured from 24-hour urine collection)
Key exclusion criteria (5 listed)
- The presence of significant pleural effusion or ascites
- Prior systemic chemotherapy for urothelial carcinoma including neoadjuvant chemotherapy (prior intravesical therapy is permitted)
- History of malignancy within preceding 5 years, aside from non-melanoma skin cancer or previously treated or incidentally detected prostate cancer with undetectable PSA (after radical cystectomy or prostate cancer therapy)
- Peripheral neuropathy greater than grade 1
- The presence of active heart disease such as congestive heart failure or unstable angina
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 |
|---|---|---|
| cisplatinAlso: CACP, CDDP, CPDD, DDPGiven IV | Drug | Arm A (gemcitabine hydrochloride, cisplatin), Arm B (MVAC) |
| gemcitabine hydrochlorideAlso: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, GemzarGiven IV | Drug | Arm A (gemcitabine hydrochloride, cisplatin) |
| methotrexateAlso: amethopterin, Folex, methylaminopterin, MexateGiven IV | Drug | Arm B (MVAC) |
| vinblastineAlso: Velban, Velsar, VLBGiven IV | Drug | Arm B (MVAC) |
| doxorubicin hydrochlorideAlso: ADM, ADR, Adria, Adriamycin PFSGiven IV | Drug | Arm B (MVAC) |
| pegfilgrastimAlso: Filgrastim SD-01, GCSF-SD01, Neulasta, SD-01 sustained duration G-CSFGiven SC | Biological | Arm B (MVAC) |
| laboratory biomarker analysisCorrelative studies | Other | Arm A (gemcitabine hydrochloride, cisplatin), Arm B (MVAC) |
Primary outcome
Rate of unacceptable toxicity graded according to Common Terminology Criteria (CTC) v4.0
Time frame: Assessed up to 3 years
80% confidence intervals (CI) will be constructed; for unacceptable toxicity, the confidence interval will be one-sided.
1 secondary outcome
Disease-free survival
Time frame: From radical cystectomy to the time cancer recurrence is detected by clinical findings or during surveillance imaging, at 3 years
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 29 Jan 2014.
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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.
Tanya Dorff principal investigator
University of Southern California
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cisplatin, gemcitabine hydrochloride and methotrexate in people with Anterior Urethral Cancer and Localized Transitional Cell Cancer of the Renal Pelvis and Ureter, run by University of Southern California.
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 17 inclusion and 5 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 29 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
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?
Rate of unacceptable toxicity graded according to Common Terminology Criteria (CTC) v4.0 (time frame: Assessed up to 3 years). 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 29 Jan 2014.