Bladder CancerNCT04245618
Neoadjuvant Chemotherapy in Non Muscle Invasive T1b Bladder Cancer
An observational study of Bladder Cancer, run by Assiut University.
Trial summary
The aim of our study is to evaluate the benefit of NAC in T1b NMIBC . Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- neoadjuvant chemotherapy ( cisplatin - gemcitabine)
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- Jul 2020to Sep 2021
- Phase
- Observational
- 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 to 75 years
- All sexes
- Adult, Older adult
Study population: Patients older than 18 years confirmed to have T1b Non muscle invasive bladder cancer by biopsy will take neoadjuvant chemotherapy
Who may be able to join
- Patient who are older than 18 years old.
- Histologically confirmed to have Non-muscle invasive bladder cancer, T1bN0M0 ,clinically and radiologically confirmed to have bladder cancer.
- Patient should have Eastern Cooperative Oncology Group performances status (ECOG)0-1 with adequate hematologic, hepatic and renal functions including hemoglobin>10 /dl, absolute neutrophil count ≥1,500/mm3, platelets ≥100,000/mm3, serum bilirubin <2 mg/dl ,both Alanine transaminase( ALT) and aspartate aminotransferase( AST) ≤2× upper limit of normal (ULN), alkaline phosphates ≤5×ULN,and serum creatinine ≤1.5 mg/dl or creatinine clearance ≥60 ml/min.
Who cannot join
- Patients with radiographic evidence of nodal or distant metastases.
- A past history of upper tract disease, neuroendocrine features.
- Non-cisplatin-based NAC .
- Prior radiation therapy to their pelvis.
- A palpable three-dimensional mass on EUA.
- Known to be stage 0, T1a, II, III, IV.
- Active serious infection, or a psychiatric illness that would preclude obtaining informed consent or history of cardiac disease will be excluded.
Trial locations and contacts
No sites are listed yet.
abeer fayek, professor contact
About this study
Official title: Role of Neoadjuvant Chemotherapy in the Conservative Management of Non-muscle Invasive Bladder Cancer (NMIBC) T1b
The aim of our study is to evaluate the benefit of NAC in T1b NMIBC .
Read the detailed description
Bladder cancer (BC) is the most common malignancy of the urinary tract and the fourth most frequent cancer in the United States, with 79,030 new cases and 16,870 deaths estimated for 2017.
The most common presenting symptom is hematuria, which occurs in about 85% of patients. Hematuria is typically intermittent, gross, and painless. Bladder irritability, usually presenting as urinary frequency, urgency, and dysuria, occurs in about 20% of patients.
Initial diagnostic workup usually involves cystoscopy and urine cytology. Cystoscopy is the gold standard for the initial diagnosis and staging of bladder cancer. If a bladder mass is detected, a transurethral resection of the bladder tumor (TURBT) is performed for full primary tumor staging. The resected bladder tumor specimen should include muscle to fully assess the depth of tumor invasion. If carcinoma in situ (CIS) is detected, multiple random biopsies, including several different areas of the bladder and the prostatic urethra, may be required to assess the extent of involvement.
Abdominal imaging with either CT or MRI is recommended in patients with a high-grade tumor or muscle invasive disease to assess for local lymph node involvement, loco regional extent of disease and the presence of hydronephrosis.
Approximately 75% of patients with urothelial carcinoma of the bladder present with non-muscle-invasive bladder cancer (NMIBC), either confined to the mucosa (Ta and carcinoma in situ [CIS]) or invading the lamina propria (T1) . Clinical T1 high-grade (cT1HG) NMIBC has the highest rate of local recurrence and carries a significant risk of disease progression, clinical understaging, and death from urothelial carcinoma (UC) . The standard of care for adequately resected cT1HG NMIBC is intravesical Bacillus Calmette-Guerin (BCG) with early radical cystectomy (RC) for recurrent or refractory cT1HG disease Pathological upstaging to pathological tumor -2( pT2) is reported in approximately 50% when muscularis propria is absent from the original biopsy, and up to 25% will have lymph node (LN) metastases , which significantly increases the risk for cancer-specific death . These observations imply that a subset of patients with NMIBC that invades into the lamina propria is at a higher risk for clinical understaging and death from UC and may benefit from more aggressive therapy.
Long-term surveillance thus remains the cornerstone of long-term management, and cystoscopy has represented the gold standard modality for over 80 years.
Cisplatin- Gemcitabine (CG) neoadjuvant chemotherapy (NAC) provides pathological downstaging and improved overall survival (OS) for patients with muscle-invasive bladder cancer (MIBC) undergoing RC.
Chemotherapy administered in a neoadjuvant setting comes with some advantages: the ability to deliver effective systemic therapy while the burden of micrometastatic disease is low and is given in a setting in which the patient's performance status is optimal (patient more fit, no loss of renal function, eligibility to optimal cisplatin-based chemotherapy regimens).
High risk features (HRFs) in NMIBC were defined as follows: lymph-vascular invasion (LVI), thickening or induration on Examination under anesthesia( EUA) , tumor-associated hydronephrosis, and variant histology. Tumors with a primary urothelial component and presence of micropapillary, squamous, sarcomatoid, nested variant, glandular, plasmacytoid, adenocarcinoma, or lymphoepithelioma components were classified as tumors of variant histology ( ,also T1b substage has bad prognosis.
The investigators hypothesized that similar high-risk features (HRFs) might identify a high-risk subset of UC patients that could benefit from NAC in the absence of evidence for muscle invasion.
- Conditions
- Bladder Cancer
- Being tested
- neoadjuvant chemotherapy ( cisplatin - gemcitabine)
- 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.
neoadjuvant chemotherapy ( cisplatin - gemcitabine)Drug
Also called cisplatin - gemzar
Neoadjuvant chemotherapy before TURBT
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the benefit of NAC in T1b NMIBC .
assessment of the response in correlation with high risk features.
Measured: baseline
Secondary outcomes (1)
Overall survival (OS) and disease-specific survival (DSS).
Overall survival (OS) and disease-specific survival (DSS).
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2020
- Study startJul 2020 (estimated)
- Primary completionJul 2021 (estimated)
- Study completionSep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, heba mahmoud mohamed, Assiut University
- Investigators
- hoda essa, professor, Study director, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04245618
- Sponsor's protocol ID
- NAC in T1 Bladder cancer
- Status last verified
- Jan 2020
- First submitted
- 26 Jan 2020
- Last updated
- 30 Jan 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Cambier S, Sylvester RJ, Collette L, Gontero P, Brausi MA, van Andel G, Kirkels WJ, Silva FC, Oosterlinck W, Prescott S, Kirkali Z, Powell PH, de Reijke TM, Turkeri L, Collette S, Oddens J. EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease-specific and Overall Survival in Non-Muscle-invasive Stage Ta-T1 Urothelial Bladder Cancer Patients Treated with 1-3 Years of Maintenance Bacillus Calmette-Guerin. Eur Urol. 2016 Jan;69(1):60-9. doi: 10.1016/j.eururo.2015.06.045. Epub 2015 Jul 23.
PubMed 26210894Tarin TV, Power NE, Ehdaie B, Sfakianos JP, Silberstein JL, Savage CJ, Sjoberg D, Dalbagni G, Bochner BH. Lymph node-positive bladder cancer treated with radical cystectomy and lymphadenectomy: effect of the level of node positivity. Eur Urol. 2012 May;61(5):1025-30. doi: 10.1016/j.eururo.2012.01.049. Epub 2012 Feb 7.
PubMed 22342773Chahal R, Harrison SC. Re: an interval longer than 12 weeks between the diagnosis of muscle invasion and cystectomy is associated with worse outcome in bladder carcinoma. J Urol. 2003 Oct;170(4 Pt 1):1327; author reply 1327. No abstract available.
PubMed 14515867Black PC, Brown GA, Dinney CP. The impact of variant histology on the outcome of bladder cancer treated with curative intent. Urol Oncol. 2009 Jan-Feb;27(1):3-7. doi: 10.1016/j.urolonc.2007.07.010. Epub 2008 Jan 14.
PubMed 18367107Otto W, van Rhijn BW, Breyer J, Bertz S, Eckstein M, Mayr R, Lausenmeyer EM, Denzinger S, Burger M, Hartmann A. Infiltrative lamina propria invasion pattern as an independent predictor for cancer-specific and overall survival of instillation treatment-naive stage T1 high-grade urothelial bladder cancer. Int J Urol. 2018 May;25(5):442-449. doi: 10.1111/iju.13532. Epub 2018 Feb 22.
PubMed 29473226Babjuk M, Burger M, Comperat EM, Gontero P, Mostafid AH, Palou J, van Rhijn BWG, Roupret M, Shariat SF, Sylvester R, Zigeuner R, Capoun O, Cohen D, Escrig JLD, Hernandez V, Peyronnet B, Seisen T, Soukup V. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ) - 2019 Update. Eur Urol. 2019 Nov;76(5):639-657. doi: 10.1016/j.eururo.2019.08.016. Epub 2019 Aug 20.
PubMed 31443960Martin-Doyle W, Leow JJ, Orsola A, Chang SL, Bellmunt J. Improving selection criteria for early cystectomy in high-grade t1 bladder cancer: a meta-analysis of 15,215 patients. J Clin Oncol. 2015 Feb 20;33(6):643-50. doi: 10.1200/JCO.2014.57.6967. Epub 2015 Jan 5.
PubMed 25559810Yoshida S, Koga F, Kobayashi S, Ishii C, Tanaka H, Tanaka H, Komai Y, Saito K, Masuda H, Fujii Y, Kawakami S, Kihara K. Role of diffusion-weighted magnetic resonance imaging in predicting sensitivity to chemoradiotherapy in muscle-invasive bladder cancer. Int J Radiat Oncol Biol Phys. 2012 May 1;83(1):e21-7. doi: 10.1016/j.ijrobp.2011.11.065. Epub 2012 Mar 11.
PubMed 22414281
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Neoadjuvant Chemotherapy in the Conservative Management of Non-muscle Invasive Bladder Cancer (NMIBC) T1b
- ClinicalTrials.gov ID
- NCT04245618
- Acronym / sponsor ID
- NAC in T1 Bladder cancer
- Conditions
- Bladder Cancer
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- Jul 2020 (estimated)
- Primary completion
- Jul 2021 (estimated)
- Study completion
- Sep 2021 (estimated)
- First posted
- 29 Jan 2020 (actual)
- 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.
The aim of our study is to evaluate the benefit of NAC in T1b NMIBC .
Detailed description
Bladder cancer (BC) is the most common malignancy of the urinary tract and the fourth most frequent cancer in the United States, with 79,030 new cases and 16,870 deaths estimated for 2017.
The most common presenting symptom is hematuria, which occurs in about 85% of patients. Hematuria is typically intermittent, gross, and painless. Bladder irritability, usually presenting as urinary frequency, urgency, and dysuria, occurs in about 20% of patients.
Initial diagnostic workup usually involves cystoscopy and urine cytology. Cystoscopy is the gold standard for the initial diagnosis and staging of bladder cancer. If a bladder mass is detected, a transurethral resection of the bladder tumor (TURBT) is performed for full primary tumor staging. The resected bladder tumor specimen should include muscle to fully assess the depth of tumor invasion. If carcinoma in situ (CIS) is detected, multiple random biopsies, including several different areas of the bladder and the prostatic urethra, may be required to assess the extent of involvement.
Abdominal imaging with either CT or MRI is recommended in patients with a high-grade tumor or muscle invasive disease to assess for local lymph node involvement, loco regional extent of disease and the presence of hydronephrosis.
Approximately 75% of patients with urothelial carcinoma of the bladder present with non-muscle-invasive bladder cancer (NMIBC), either confined to the mucosa (Ta and carcinoma in situ [CIS]) or invading the lamina propria (T1) . Clinical T1 high-grade (cT1HG) NMIBC has the highest rate of local recurrence and carries a significant risk of disease progression, clinical understaging, and death from urothelial carcinoma (UC) . The standard of care for adequately resected cT1HG NMIBC is intravesical Bacillus Calmette-Guerin (BCG) with early radical cystectomy (RC) for recurrent or refractory cT1HG disease Pathological upstaging to pathological tumor -2( pT2) is reported in approximately 50% when muscularis propria is absent from the original biopsy, and up to 25% will have lymph node (LN) metastases , which significantly increases the risk for cancer-specific death . These observations imply that a subset of patients with NMIBC that invades into the lamina propria is at a higher risk for clinical understaging and death from UC and may benefit from more aggressive therapy.
Long-term surveillance thus remains the cornerstone of long-term management, and cystoscopy has represented the gold standard modality for over 80 years.
Cisplatin- Gemcitabine (CG) neoadjuvant chemotherapy (NAC) provides pathological downstaging and improved overall survival (OS) for patients with muscle-invasive bladder cancer (MIBC) undergoing RC.
Chemotherapy administered in a neoadjuvant setting comes with some advantages: the ability to deliver effective systemic therapy while the burden of micrometastatic disease is low and is given in a setting in which the patient's performance status is optimal (patient more fit, no loss of renal function, eligibility to optimal cisplatin-based chemotherapy regimens).
High risk features (HRFs) in NMIBC were defined as follows: lymph-vascular invasion (LVI), thickening or induration on Examination under anesthesia( EUA) , tumor-associated hydronephrosis, and variant histology. Tumors with a primary urothelial component and presence of micropapillary, squamous, sarcomatoid, nested variant, glandular, plasmacytoid, adenocarcinoma, or lymphoepithelioma components were classified as tumors of variant histology ( ,also T1b substage has bad prognosis.
The investigators hypothesized that similar high-risk features (HRFs) might identify a high-risk subset of UC patients that could benefit from NAC in the absence of evidence for muscle invasion.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patients older than 18 years confirmed to have T1b Non muscle invasive bladder cancer by biopsy will take neoadjuvant chemotherapy
Key inclusion criteria (3 listed)
- Patient who are older than 18 years old.
- Histologically confirmed to have Non-muscle invasive bladder cancer, T1bN0M0 ,clinically and radiologically confirmed to have bladder cancer.
- Patient should have Eastern Cooperative Oncology Group performances status (ECOG)0-1 with adequate hematologic, hepatic and renal functions including hemoglobin>10 /dl, absolute neutrophil count ≥1,500/mm3, platelets ≥100,000/mm3, serum bilirubin <2 mg/dl ,both Alanine transaminase( ALT) and aspartate aminotransferase( AST) ≤2× upper limit of normal (ULN), alkaline phosphates ≤5×ULN,and serum creatinine ≤1.5 mg/dl or creatinine clearance ≥60 ml/min.
Key exclusion criteria (7 listed)
- Patients with radiographic evidence of nodal or distant metastases.
- A past history of upper tract disease, neuroendocrine features.
- Non-cisplatin-based NAC .
- Prior radiation therapy to their pelvis.
- A palpable three-dimensional mass on EUA.
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 chemotherapy ( cisplatin - gemcitabine)Also: cisplatin - gemzarNeoadjuvant chemotherapy before TURBT | Drug | – |
Primary outcome
Evaluation of the benefit of NAC in T1b NMIBC .
Time frame: baseline
assessment of the response in correlation with high risk features.
1 secondary outcome
Overall survival (OS) and disease-specific survival (DSS).
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2020.
- Background: PubMed 26210894Cambier S, Sylvester RJ, Collette L, Gontero P, Brausi MA, van Andel G, Kirkels WJ, Silva FC, Oosterlinck W, Prescott S, Kirkali Z, Powell PH, de Reijke TM, Turkeri L, Collette S, Oddens J. EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease-specific and Overall Survival in Non-Muscle-invasive Stage Ta-T1 Urothelial Bladder Cancer Patients Treated with 1-3 Years of Maintenance Bacillus Calmette-Guerin. Eur Urol. 2016 Jan;69(1):60-9. doi: 10.1016/j.eururo.2015.06.045. Epub 2015 Jul 23.
- Background: PubMed 22342773Tarin TV, Power NE, Ehdaie B, Sfakianos JP, Silberstein JL, Savage CJ, Sjoberg D, Dalbagni G, Bochner BH. Lymph node-positive bladder cancer treated with radical cystectomy and lymphadenectomy: effect of the level of node positivity. Eur Urol. 2012 May;61(5):1025-30. doi: 10.1016/j.eururo.2012.01.049. Epub 2012 Feb 7.
- Background: PubMed 14515867Chahal R, Harrison SC. Re: an interval longer than 12 weeks between the diagnosis of muscle invasion and cystectomy is associated with worse outcome in bladder carcinoma. J Urol. 2003 Oct;170(4 Pt 1):1327; author reply 1327. No abstract available.
- Background: PubMed 18367107Black PC, Brown GA, Dinney CP. The impact of variant histology on the outcome of bladder cancer treated with curative intent. Urol Oncol. 2009 Jan-Feb;27(1):3-7. doi: 10.1016/j.urolonc.2007.07.010. Epub 2008 Jan 14.
- Background: PubMed 29473226Otto W, van Rhijn BW, Breyer J, Bertz S, Eckstein M, Mayr R, Lausenmeyer EM, Denzinger S, Burger M, Hartmann A. Infiltrative lamina propria invasion pattern as an independent predictor for cancer-specific and overall survival of instillation treatment-naive stage T1 high-grade urothelial bladder cancer. Int J Urol. 2018 May;25(5):442-449. doi: 10.1111/iju.13532. Epub 2018 Feb 22.
- Background: PubMed 31443960Babjuk M, Burger M, Comperat EM, Gontero P, Mostafid AH, Palou J, van Rhijn BWG, Roupret M, Shariat SF, Sylvester R, Zigeuner R, Capoun O, Cohen D, Escrig JLD, Hernandez V, Peyronnet B, Seisen T, Soukup V. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ) - 2019 Update. Eur Urol. 2019 Nov;76(5):639-657. doi: 10.1016/j.eururo.2019.08.016. Epub 2019 Aug 20.
- Background: PubMed 25559810Martin-Doyle W, Leow JJ, Orsola A, Chang SL, Bellmunt J. Improving selection criteria for early cystectomy in high-grade t1 bladder cancer: a meta-analysis of 15,215 patients. J Clin Oncol. 2015 Feb 20;33(6):643-50. doi: 10.1200/JCO.2014.57.6967. Epub 2015 Jan 5.
- Background: PubMed 22414281Yoshida S, Koga F, Kobayashi S, Ishii C, Tanaka H, Tanaka H, Komai Y, Saito K, Masuda H, Fujii Y, Kawakami S, Kihara K. Role of diffusion-weighted magnetic resonance imaging in predicting sensitivity to chemoradiotherapy in muscle-invasive bladder cancer. Int J Radiat Oncol Biol Phys. 2012 May 1;83(1):e21-7. doi: 10.1016/j.ijrobp.2011.11.065. Epub 2012 Mar 11.
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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.
abeer fayek, professor contact
hoda essa, professor study director
Assiut University
Questions about this trial
What is this clinical trial studying?
An observational study of Bladder Cancer, run by Assiut University.
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 3 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: status not confirmed, as of the sponsor's last update on 30 Jan 2020. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Heba sheha, MD (+201005054776, beboo0412@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of the benefit of NAC in T1b NMIBC . (time frame: baseline). 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 NCT04245618, which also lists 8 linked publications.
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 30 Jan 2020.