Distal Urethral CancerPhase 2NCT01611662
Gemcitabine Hydrochloride and Cisplatin Before Surgery in Treating Patients With Muscle Invasive Bladder Cancer
A Phase 2 study testing gemcitabine hydrochloride, cisplatin and therapeutic conventional surgery in people with Distal Urethral Cancer and Proximal Urethral Cancer, run by Fox Chase Cancer Center at 2 sites in United States.
Trial summary
The purpose of this research study is to find out what effects, good and/or bad, dose-dense (every 14 days) chemotherapy with gemcitabine (gemcitabine hydrochloride) and cisplatin given before surgery have on patients and their muscle invasive bladder cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Distal Urethral Cancer, Proximal Urethral Cancer, Squamous Cell Carcinoma of the Bladder
- What is being tested?
- gemcitabine hydrochloride, cisplatin and therapeutic conventional surgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 2 sitesUnited States
- Study dates
- 29 May 2012to 22 Jan 2019
- 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 histologically confirmed urothelial carcinoma of the bladder or urethra; patients with urothelial carcinoma of the prostatic urethra only may be included at primary investigator (PI) discretion; T-stage must be T2 to T4a; patients with radiographic N0 disease or N1 disease are eligible for the study; patients must not have radiographic evidence of metastatic disease; mixed histologies which are predominantly urothelial, such as with squamous or micropapillary differentiation, are allowed so long as there is no component of small cell histology; histology must be confirmed by a pathologist at an institution involved in this study
- Patients must be candidates for radical cystectomy with the goal of cure
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
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- Total bilirubin =< institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional ULN
- Patients must have adequate renal function defined as creatinine clearance >= 50 mL/min; for eligibility, creatinine clearance may be either calculated using the Cockcroft-Gault formula or measured with 24 hour urine collection; note that 24 hour urine collection is required at baseline, but does not have to be used for eligibility if calculated clearance by Cockcroft-Gault is preferred; nephrostomy or ureteral stent placement in order to achieve adequate creatinine clearance is allowed
- Women of child-bearing potential (WOCBP) and men with a female partner who is a WOCBP must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting prior to beginning treatment and continuing until at least 3 months after last dose of chemotherapy and surgery; should a woman become pregnant or suspect she is pregnant while participating in this study or if a female partner of a man participating in this study becomes pregnant, the treating physician must be notified immediately; WOCBP must have a negative serum or urine pregnancy test within 7 days prior to initiating study treatment
- No other active malignancy
- Ability to understand and the willingness to sign written informed consent and Health Insurance Portability and Accountability Act (HIPAA) documents
Who cannot join
- Patients who have had intravesicular therapy within 4 weeks of study entry, or those who have not recovered from adverse effects of such agents administered more than 4 weeks earlier
- Patients may not be receiving any investigational agents within 4 weeks of study entry
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or cisplatin or other agents used in the study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study
- Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- Patients who have undergone prior radiation to greater than or equal to 25% of the bone marrow within the past year are excluded
- Patients who have received any previous systemic chemotherapy or radiation therapy for urothelial carcinoma within 1 year of study entry are ineligible
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Thomas Jefferson University, Kimmel Cancer Center
Philadelphia, Pennsylvania, 19107
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497
About this study
Official title: Phase II Trial of Neoadjuvant Dose Dense Gemcitabine and Cisplatin In Muscle Invasive Bladder Cancer
The purpose of this research study is to find out what effects, good and/or bad, dose-dense (every 14 days) chemotherapy with gemcitabine (gemcitabine hydrochloride) and cisplatin given before surgery have on patients and their muscle invasive bladder cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the rate of complete response (pT0) at cystectomy following preoperative dose dense gemcitabine and cisplatin (DD GC) in patients with muscle invasive urothelial carcinoma of the bladder.
SECONDARY OBJECTIVES:
- To assess the toxicity profile of DD GC when given in the neoadjuvant setting: To define the number of patients who complete all three cycles of treatment without dose reduction, and to describe the incidence of toxicity.
II. To assess the 5 year overall and relapse free survival in patients who receive neoadjuvant DD GC.
TERTIARY OBJECTIVES:
- To evaluate tissue specimens from patients to assess for molecular markers that correlate with clinical outcome.
OUTLINE:
Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1 and cisplatin IV on day 1 or divided over days 1 and 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-8 weeks after chemotherapy, patients undergo radical cystectomy.
After completion of study treatment, patients are followed up for 5 years.
- Conditions
- Distal Urethral Cancer, Proximal Urethral Cancer, Squamous Cell Carcinoma of the Bladder, Stage II Bladder Cancer, Stage III Bladder Cancer, Urethral Cancer Associated With Invasive Bladder Cancer
- Being tested
- gemcitabine hydrochloride, cisplatin, therapeutic conventional surgery, laboratory biomarker analysis
- 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.
Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Given IV
cisplatinDrug
Also called CACP, CDDP, CPDD, DDP
Given IV
therapeutic conventional surgeryProcedure or surgery
Undergo radical cystectomy
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (gemcitabine hydrochloride, cisplatin, surgery) | Experimental | Patients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and cisplatin IV on day 1 or divided over days 1 and 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-8 weeks after chemotherapy, patients undergo radical cystectomy. Receives: Drug: gemcitabine hydrochloride; Drug: cisplatin; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Complete Response Rate Following Chemotherapy Before Surgery
Pathological response rate following neoadjuvant chemotherapy was assessed by TNM staging at the time of radical cystectomy
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2012 (estimated)
- Study start29 May 2012
- Primary completion12 Jul 2013
- Study completion22 Jan 2019
Why it stopped: Extreme Toxicity
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Distal Urethral CancerStudies of the same condition, open and under way.
- More trials run by Fox Chase 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
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elizabeth Plimack, Principal investigator, Fox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01611662
- Sponsor's protocol ID
- ERP-GU-052
- Other IDs
- NCI-2012-00906, IRB#12-015, ERP-GU-052
- Status last verified
- Jul 2019
- First submitted
- 30 May 2012
- Last updated
- 29 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Satyal U, Valentine H, Liu D, Slifker M, Lallas CD, Trabulsi EJ, Bukavina L, Szeto L, Hoffman-Censits JH, Mouw KW, Faltas BM, Grivas P, Ibragimova I, Porten SP, Van Allen EM, Geynisman DM, Parker DC, O'Neill JP, Drevik J, Christianson SS, Ginzburg S, Correa AF, Uzzo RG, Ross EA, Zibelman MR, Ghatalia P, Plimack ER, Kutikov A, Abbosh PH. Urine Biopsy as Dynamic Biomarker to Enhance Clinical Staging of Bladder Cancer in Radical Cystectomy Candidates. JCO Precis Oncol. 2024 Jun;8:e2300362. doi: 10.1200/PO.23.00362.
PubMed 38865671
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Neoadjuvant Dose Dense Gemcitabine and Cisplatin In Muscle Invasive Bladder Cancer
- ClinicalTrials.gov ID
- NCT01611662
- Acronym / sponsor ID
- ERP-GU-052
- Conditions
- Distal Urethral Cancer, Proximal Urethral Cancer, Squamous Cell Carcinoma of the Bladder, Stage II Bladder Cancer, Stage III Bladder Cancer, Urethral Cancer Associated With Invasive Bladder Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Extreme Toxicity
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Study start
- 29 May 2012 (actual)
- Primary completion
- 12 Jul 2013 (actual)
- Study completion
- 22 Jan 2019 (actual)
- First posted
- 5 Jun 2012 (estimated)
- Results
- Posted 6 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to find out what effects, good and/or bad, dose-dense (every 14 days) chemotherapy with gemcitabine (gemcitabine hydrochloride) and cisplatin given before surgery have on patients and their muscle invasive bladder cancer.
Detailed description
PRIMARY OBJECTIVES:
- To assess the rate of complete response (pT0) at cystectomy following preoperative dose dense gemcitabine and cisplatin (DD GC) in patients with muscle invasive urothelial carcinoma of the bladder.
SECONDARY OBJECTIVES:
- To assess the toxicity profile of DD GC when given in the neoadjuvant setting: To define the number of patients who complete all three cycles of treatment without dose reduction, and to describe the incidence of toxicity.
II. To assess the 5 year overall and relapse free survival in patients who receive neoadjuvant DD GC.
TERTIARY OBJECTIVES:
- To evaluate tissue specimens from patients to assess for molecular markers that correlate with clinical outcome.
OUTLINE:
Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1 and cisplatin IV on day 1 or divided over days 1 and 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-8 weeks after chemotherapy, patients undergo radical cystectomy.
After completion of study treatment, patients are followed up for 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (gemcitabine hydrochloride, cisplatin, surgery) | Experimental | Drug: gemcitabine hydrochloride, Drug: cisplatin, Procedure: therapeutic conventional surgery, Other: laboratory biomarker analysisPatients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and cisplatin IV on day 1 or divided over days 1 and 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-8 weeks after chemotherapy, patients undergo radical cystectomy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients must have histologically confirmed urothelial carcinoma of the bladder or urethra; patients with urothelial carcinoma of the prostatic urethra only may be included at primary investigator (PI) discretion; T-stage must be T2 to T4a; patients with radiographic N0 disease or N1 disease are eligible for the study; patients must not have radiographic evidence of metastatic disease; mixed histologies which are predominantly urothelial, such as with squamous or micropapillary differentiation, are allowed so long as there is no component of small cell histology; histology must be confirmed by a pathologist at an institution involved in this study
- Patients must be candidates for radical cystectomy with the goal of cure
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
Key exclusion criteria (8 listed)
- Patients who have had intravesicular therapy within 4 weeks of study entry, or those who have not recovered from adverse effects of such agents administered more than 4 weeks earlier
- Patients may not be receiving any investigational agents within 4 weeks of study entry
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or cisplatin or other agents used in the study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study
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 |
|---|---|---|
| gemcitabine hydrochlorideAlso: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, GemzarGiven IV | Drug | Treatment (gemcitabine hydrochloride, cisplatin, surgery) |
| cisplatinAlso: CACP, CDDP, CPDD, DDPGiven IV | Drug | Treatment (gemcitabine hydrochloride, cisplatin, surgery) |
| therapeutic conventional surgeryUndergo radical cystectomy | Procedure or surgery | Treatment (gemcitabine hydrochloride, cisplatin, surgery) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (gemcitabine hydrochloride, cisplatin, surgery) |
Primary outcome
Pathological Complete Response Rate Following Chemotherapy Before Surgery
Time frame: Up to 5 years
Pathological response rate following neoadjuvant chemotherapy was assessed by TNM staging at the time of radical cystectomy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38865671Satyal U, Valentine H, Liu D, Slifker M, Lallas CD, Trabulsi EJ, Bukavina L, Szeto L, Hoffman-Censits JH, Mouw KW, Faltas BM, Grivas P, Ibragimova I, Porten SP, Van Allen EM, Geynisman DM, Parker DC, O'Neill JP, Drevik J, Christianson SS, Ginzburg S, Correa AF, Uzzo RG, Ross EA, Zibelman MR, Ghatalia P, Plimack ER, Kutikov A, Abbosh PH. Urine Biopsy as Dynamic Biomarker to Enhance Clinical Staging of Bladder Cancer in Radical Cystectomy Candidates. JCO Precis Oncol. 2024 Jun;8:e2300362. doi: 10.1200/PO.23.00362.
Related trials for Distal Urethral Cancer
Active, not recruitingPhase 2
Fluorouracil, Leucovorin, Gemcitabine, and Cisplatin in Treating Patients With Metastatic or Unresectable Adenocarcinoma of the Urothelium or Urachal Remnant
Bladder Cancer, Urethral Cancer
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.
Elizabeth Plimack principal investigator
Fox Chase Cancer Center
2 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 gemcitabine hydrochloride, cisplatin and therapeutic conventional surgery in people with Distal Urethral Cancer and Proximal Urethral Cancer, run by Fox Chase Cancer Center at 2 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 12 inclusion and 8 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 29 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 6 Apr 2017). 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?
Pathological Complete Response Rate Following Chemotherapy Before Surgery (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01611662, which also lists 1 linked publication.
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 Jul 2019.