Urothelial CarcinomaPhase 2NCT05137262
A Phase II Multicenter Study of Chemotherapy Versus Chemotherapy Plus Durvalumab (MEDI 4736) in Patients With Lymph Node Positive Urothelial Carcinoma of the Bladder
A Phase 2 study testing Abiraterone acetate, Durvalumab and Methotrexate in people with Urothelial Carcinoma and Bladder Cancer, run by M.D. Anderson Cancer Center at 2 sites in United States.
Trial summary
This is a phase II randomized study of standard of care (SOC) neo-adjuvant cisplatin chemotherapy (NAC) versus NAC plus durvalumab in patients with either clinical or pathologic intra-pelvic node-positive urothelial carcinoma of the bladder. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma, Bladder Cancer
- What is being tested?
- Abiraterone acetate, Durvalumab and Methotrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Oct 2021to 31 Aug 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 histological diagnosis of urothelial carcinoma of the bladder and must meet criteria for stage cTanyN1-3M0 disease via AJCC 8th edition staging criteria30
- Patients must provide tissue by agreeing to transurethethral biopsy of the bladder and the lymph node prior to initiating treatment. If patient is unable or unwilling to undergo biopsy at screening and tissue is available, patient may be eligibile per PI discretion.
- Patients must be ≥18 years of age.
- Patients must have pelvic lymph node amenable for biopsy as assessed by treating MD and interventional radiologist.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
- Patients must have a life expectancy of at least 12 weeks.
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- Patients must have body weight >30 kg.
- Left ventricular ejection fraction ≥ 50%.
- Adequate organ function as defined below:
- Hematological i. Absolute neutrophil count (ANC) ≥ 1,500/mcL. ii. Platelets ≥100,000 / mcL. iii. Hemoglobin ≥9 g/dL
- Renal iv. Creatinine clearance > 50 ml/min as calculated by the Cockgroft Gault formula as:
- 1. CLCR = {[(140-age) × weight)]/(72 x SCR) × 0.85 (if female), where CLCR (creatinine clearance) is measured in mL/min, age is expressed in years, weight in kilograms (kg), and SCR (serum creatinine) in mg/dL.
- Hepatic v. Serum total bilirubin ≤1.5xULN OR Direct bilirubin ≤ULN for subjects with total bilirubin levels >1.5xULN. vi. AST and ALT ≤2.5xULN OR ≤5xULN for subjects with liver metastases.
- Coagulation vii. International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5xULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. viii. Activated Partial Thromboplastin Time (aPTT) ≤1.5xULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
- Women of child-bearing potential MUST have a negative serum or urine HCG test unless prior tubal ligation (>/= 1 year before screening), total hysterectomy or menopause (defined as 12 consecutive months of amenorrhea). Patients should not become pregnant or breastfeed while on this study. Sexually active patients must agree to use dual contraception for the duration of study participation and for 90 days after receipt of last drug on active treatment.
- Ability to understand and willingness to sign informed consent from prior to initiation of the study and any study procedures.
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Who cannot join
- Has metastatic disease to lymph nodes outside of the pelvis or to visceral sites as seen on imaging.
- CTCAE v5.0 Grade ≥ 2 neuropathy.
- CTCAE v5.0 Grade ≥ 2 hearing loss.
- New York Heart Association (NYHA) Class III or IV heart failure defined as:
- Class III heart failure is defined as: patients with cardiac disease resulting in marked limitation of physical activity and/or less than ordinary activity causes fatigue. Patients are comfortable only at rest.
- Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases
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- Known active Hepatitis B, Hepatitis C infection (HCV-DNA positive), or HIV infection.
- Current or prior use of immunosuppressive medication within 28 days before the first dose of study drug, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from chemotherapy and/or immunotherapy delivered as part of the therapy on trial is allowed.
- Prior exposure to any anti-PD-1 or anti-PD-L1 (including durvalumab) antibody.
- Active or prior documented autoimmune disease within the past 2 years. NOTE: Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
- History of primary immunodeficiency.
- History of allogeneic organ transplant.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
- Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
- Active infection requiring intravenous (IV) antibiotics or other uncontrolled intercurrent illness requiring hospitalization. Minor infections, e.g. periodontal infection or urinary tract infection (UTI), which may be treated with short-term oral antibiotics are allowed.
- Active infection of tuberculosis, as determined by clinical signs and symptoms.
- Inability to comply with the study and follow-up procedures.
- History of CVA, myocardial infarction or unstable angina within the previous 6 months before starting therapy.
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
- Has a known additional malignancy that is progressing or requires active treatment.
- Exceptions include basal cell carcinoma of the skin, organ confined adenocarcinoma of the prostate, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Patients may not have received systemic cytotoxic chemotherapy within 1 year of study entry.
- History of exposure to immunotherapy for previous malignancy.
- Intra-vesicular 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.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to methotrexate, vinblastine, doxorubicin, cisplatin, durvalumab, or any other agents used in the study.
- Pregnant female patients; breastfeeding female patients; and female or male patients of childbearing potential who are unwilling or unable to use 2 methods of contraception for at least 90 days after the last dose of study drugs. Highly effective methods of contraception are those that alone or in combination, result in a failure rate of less than 1% per year when used consistently and correctly. These methods include:
- Established use of oral, inserted, or injected or implanted hormonal methods of contraception are allowed provided the patient remains on the same treatment throughout the entire study and has been using that hormonal contraceptive for an adequate period of time to ensure effectiveness.
- Correctly placed copper containing intrauterine device (IUD).
- Male condom or female condom used with spermicide (i.e. foam, gel, film, cream or suppository).
- Male sterilization with appropriately confirmed absence of sperm in the post vasectomy ejaculate.
- Bilateral tubal ligation or bilateral oophorectomy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Indiana University
Bloomington, Indiana, 47405
M D Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Durvalumab and Standard Chemotherapy for the Treatment of Lymph Node Positive Bladder Cancer
This is a phase II randomized study of standard of care (SOC) neo-adjuvant cisplatin chemotherapy (NAC) versus NAC plus durvalumab in patients with either clinical or pathologic intra-pelvic node-positive urothelial carcinoma of the bladder. Patients with cTanyN1-3M0 via American Joint Committee on Cancer (AJCC) 8th edition staging30 will be considered tor enrollment in this trial. We plan to enroll 60 patients. Patients will be randomized 2:1 to the intervention arm with durvalumab plus NAC vs SOC NAC. In patients randomized to receive, durvalumab will be continued as maintenance every 4 weeks until either relapse or 1 year, whichever event occurs first.
Tissue collection will occur as a biopsy prior to initiation of neo-adjuvant therapy via both transurethral biopsy of bladder and lymph node biopsy. Tissue will again be collected at the time of radical cystectomy or, in patients who are no longer surgical candidates, in the form of biopsy as standard of care. Blood and urine will be collected at baseline, week 2, week 6, week 16, and at the 6 week-post surgery visit for analysis of correlative studies.
Read the detailed description
Primary Objective:
- To estimate the difference in pathologic complete response rate as defined as no evidence of disease (ypT0N0) or carcinoma in situ within the bladder only (ypTcisN0) in patients after administration of the combination of dose-dense MVAC and durvalumab versus dose-dense MVAC alone.
Secondary Objectives:
- To estimate the difference in the rate of patients eligible for surgical consolidation within 90 days of completion of pre-surgical treatment.
- To estimate the difference in the proportion of patients with relapse free survival at 12 and 36 months following surgery in each treatment arm.
- To estimate the difference in overall survival for both arms on study.
- To measure lymph node response with those with measurable disease via RECIST v1.1 criteria at baseline, week 6, and week 12 on study.
- To evaluate the toxicity of the combination of dose-dense MVAC chemotherapy and durvalumab.
Correlative Objectives:
- Exploratory biomarkers to study the correlation between immunological and molecular changes in tumor tissues and peripheral blood with pathologic complete response, time until relapse and rate of adverse events, with a specific emphasis upon comparison of tissue samples in patients exposed to combination dose-dense MVAC and durvalumab versus dose-dense MVAC alone
- Conditions
- Urothelial Carcinoma, Bladder Cancer
- Being tested
- Abiraterone acetate, Durvalumab, Methotrexate, Vinblastine, Doxorubicin Hydrochloride
- Medical subject headings
- Carcinoma, Transitional Cell, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abiraterone acetateOther
Also called Zytiga™
Given by IV
DurvalumabDrug
Also called MEDI4736
Given by IV
MethotrexateDrug
Given by IV
VinblastineDrug
Also called Velban
Given by IV
Also called Adriamycin RDF™, Adriamycin PFS®, Adriamycin®, Rubex®
Given by IV
CisplatinDrug
Also called Platinol®-AQ, Platinol®, CDDP
Given by IV
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Standard of Care with dose-dense MVAC | Experimental | The patient will receive treatment every 14 days for up to 6 cycles in the neoadjuvant setting. Receives: Other: Abiraterone acetate; Drug: Durvalumab; Drug: Methotrexate; Drug: Vinblastine; Drug: Doxorubicin Hydrochloride; Drug: Cisplatin |
| Arm B: Intervention with dose-dense MVAC plus Durvalumab | Experimental | Durvalumab will be administered one week prior to the initial cycle of dose-dense MVAC and then with each additional cycle of dose-dense MVAC on Arm B Receives: Other: Abiraterone acetate; Drug: Durvalumab; Drug: Methotrexate; Drug: Vinblastine; Drug: Doxorubicin Hydrochloride; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To estimate the difference in the pathologic complete response rate.
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2021
- Study start13 Oct 2021
- Primary completion31 Aug 2028 (estimated)
- Study completion31 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson 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
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Matthew Campbell, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05137262
- Sponsor's protocol ID
- 2020-1091
- Other IDs
- NCI-2021-12884
- Status last verified
- Aug 2026
- First submitted
- 16 Nov 2021
- Last updated
- 7 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Durvalumab and Standard Chemotherapy for the Treatment of Lymph Node Positive Bladder Cancer
- ClinicalTrials.gov ID
- NCT05137262
- Acronym / sponsor ID
- 2020-1091
- Conditions
- Urothelial Carcinoma, Bladder Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 12 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 13 Oct 2021 (actual)
- Primary completion
- 31 Aug 2028 (estimated)
- Study completion
- 31 Aug 2028 (estimated)
- First posted
- 30 Nov 2021 (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.
This is a phase II randomized study of standard of care (SOC) neo-adjuvant cisplatin chemotherapy (NAC) versus NAC plus durvalumab in patients with either clinical or pathologic intra-pelvic node-positive urothelial carcinoma of the bladder. Patients with cTanyN1-3M0 via American Joint Committee on Cancer (AJCC) 8th edition staging30 will be considered tor enrollment in this trial. We plan to enroll 60 patients. Patients will be randomized 2:1 to the intervention arm with durvalumab plus NAC vs SOC NAC. In patients randomized to receive, durvalumab will be continued as maintenance every 4 weeks until either relapse or 1 year, whichever event occurs first.
Tissue collection will occur as a biopsy prior to initiation of neo-adjuvant therapy via both transurethral biopsy of bladder and lymph node biopsy. Tissue will again be collected at the time of radical cystectomy or, in patients who are no longer surgical candidates, in the form of biopsy as standard of care. Blood and urine will be collected at baseline, week 2, week 6, week 16, and at the 6 week-post surgery visit for analysis of correlative studies.
Detailed description
Primary Objective:
- To estimate the difference in pathologic complete response rate as defined as no evidence of disease (ypT0N0) or carcinoma in situ within the bladder only (ypTcisN0) in patients after administration of the combination of dose-dense MVAC and durvalumab versus dose-dense MVAC alone.
Secondary Objectives:
- To estimate the difference in the rate of patients eligible for surgical consolidation within 90 days of completion of pre-surgical treatment.
- To estimate the difference in the proportion of patients with relapse free survival at 12 and 36 months following surgery in each treatment arm.
- To estimate the difference in overall survival for both arms on study.
- To measure lymph node response with those with measurable disease via RECIST v1.1 criteria at baseline, week 6, and week 12 on study.
- To evaluate the toxicity of the combination of dose-dense MVAC chemotherapy and durvalumab.
Correlative Objectives:
- Exploratory biomarkers to study the correlation between immunological and molecular changes in tumor tissues and peripheral blood with pathologic complete response, time until relapse and rate of adverse events, with a specific emphasis upon comparison of tissue samples in patients exposed to combination dose-dense MVAC and durvalumab versus dose-dense MVAC alone
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Standard of Care with dose-dense MVAC | Experimental | Other: Abiraterone acetate, Drug: Durvalumab, Drug: Methotrexate, Drug: Vinblastine, Drug: Doxorubicin Hydrochloride, Drug: CisplatinThe patient will receive treatment every 14 days for up to 6 cycles in the neoadjuvant setting. |
| Arm B: Intervention with dose-dense MVAC plus Durvalumab | Experimental | Other: Abiraterone acetate, Drug: Durvalumab, Drug: Methotrexate, Drug: Vinblastine, Drug: Doxorubicin Hydrochloride, Drug: CisplatinDurvalumab will be administered one week prior to the initial cycle of dose-dense MVAC and then with each additional cycle of dose-dense MVAC on Arm B |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients must have histological diagnosis of urothelial carcinoma of the bladder and must meet criteria for stage cTanyN1-3M0 disease via AJCC 8th edition staging criteria30
- Patients must provide tissue by agreeing to transurethethral biopsy of the bladder and the lymph node prior to initiating treatment. If patient is unable or unwilling to undergo biopsy at screening and tissue is available, patient may be eligibile per PI discretion.
- Patients must be ≥18 years of age.
- Patients must have pelvic lymph node amenable for biopsy as assessed by treating MD and interventional radiologist.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
Key exclusion criteria (30 listed)
- Has metastatic disease to lymph nodes outside of the pelvis or to visceral sites as seen on imaging.
- CTCAE v5.0 Grade ≥ 2 neuropathy.
- CTCAE v5.0 Grade ≥ 2 hearing loss.
- New York Heart Association (NYHA) Class III or IV heart failure defined as:
- Known active Hepatitis B, Hepatitis C infection (HCV-DNA positive), or HIV infection.
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 |
|---|---|---|
| Abiraterone acetateAlso: Zytiga™Given by IV | Other | Arm A: Standard of Care with dose-dense MVAC, Arm B: Intervention with dose-dense MVAC plus Durvalumab |
| DurvalumabAlso: MEDI4736Given by IV | Drug | Arm A: Standard of Care with dose-dense MVAC, Arm B: Intervention with dose-dense MVAC plus Durvalumab |
| MethotrexateGiven by IV | Drug | Arm A: Standard of Care with dose-dense MVAC, Arm B: Intervention with dose-dense MVAC plus Durvalumab |
| VinblastineAlso: VelbanGiven by IV | Drug | Arm A: Standard of Care with dose-dense MVAC, Arm B: Intervention with dose-dense MVAC plus Durvalumab |
| Doxorubicin HydrochlorideAlso: Adriamycin RDF™, Adriamycin PFS®, Adriamycin®, Rubex®Given by IV | Drug | Arm A: Standard of Care with dose-dense MVAC, Arm B: Intervention with dose-dense MVAC plus Durvalumab |
| CisplatinAlso: Platinol®-AQ, Platinol®, CDDPGiven by IV | Drug | Arm A: Standard of Care with dose-dense MVAC, Arm B: Intervention with dose-dense MVAC plus Durvalumab |
Primary outcome
To estimate the difference in the pathologic complete response rate.
Time frame: through study completion, an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2026.
- M D Anderson Cancer Center websiteLink provided by the sponsor.
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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.
Matthew Campbell principal investigator
M.D. Anderson 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 Abiraterone acetate, Durvalumab and Methotrexate in people with Urothelial Carcinoma and Bladder Cancer, run by M.D. Anderson 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 17 inclusion and 30 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: under way, not looking for participants, as of the sponsor's last update on 7 Aug 2026. 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?
This study is still under way. Results are not available in the source record yet.
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?
To estimate the difference in the pathologic complete response rate. (time frame: through study completion, an average of 1 year). 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 7 Aug 2026.