Urothelial CancerPhase 1/2DUARTNCT02891161
Durvalumab And Radiation Therapy Followed by Adjuvant Durvalumab in Patients With Urothelial Cancer (T2-4 N0-2 M0) of the Bladder
A Phase 1/2 study testing durvalumab and Radiation Therapy in people with Urothelial Cancer, run by Monika Joshi, MD at 7 sites in United States.
Trial summary
This is an open label, multi-institutional, single arm study of a phase Ib study, followed by a phase II study of durvalumab with radiation therapy (RT) in patients with urothelial cancer (UC). No randomization or blinding is involved. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Cancer
- What is being tested?
- durvalumab and Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 7 sitesUnited States
- Study dates
- 16 Nov 2016to 27 Apr 2022
- Phase
- Phase 1/2
- 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
- Phase Ib subjects must meet the following inclusion criteria:
- Locally advanced urothelial cancer of bladder with any of the following:
- T3-4, N0-2 M0, OR Tx N1-2 M0 OR T2 N1-2 M0: Treatment naïve, unresectable, OR medically unfit for surgery, OR cisplatin ineligible. T3 N0 M0 patients can be included if they are cisplatin ineligible.
- Patients who have T3-4, N0-2 M0 OR Tx N1-2 M0 OR T2 N1-2 M0 post-neoadjuvant chemotherapy who become unresectable OR medically unfit for surgery.
- Phase II subjects must meet the following inclusion criteria:
- Locally advanced urothelial cancer of bladder with any of the following:
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- T3-4, N0-2 M0 OR Tx N1-2 M0 OR T2 N1-2 M0: Treatment naïve, unresectable, OR medically unfit for surgery OR cisplatin ineligible. T3 N0 M0 patients can be included if they are cisplatin ineligible.
- T3-4, N0-1 M0 OR Tx N1-2 M0 OR T2 N1-2 M0 patients post-neoadjuvant chemotherapy who become unresectable OR medically unfit for surgery.
- T2, N0, M0 who are ineligible to get cisplatin based chemotherapy.
- All subjects:
- Written informed consent and HIPAA authorization for personal health information, obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Life expectancy of >6 months per treating physician.
- Subjects must have archival tissue available from previous TURBT (preferred) or lymph node core biopsy within 8 weeks of treatment or be assessed by the treating urologist to undergo maximal TURBT. The extent of TURBT may vary for each patient and will be determined by the treating urologist. Further, the treating urologist will decide if performing the TURBT is clinically appropriate. If the potential subject does not have tumor amenable to biopsy, there is insufficient tissue for PD-L1 testing or is not clinically appropriate for TURBT, enrollment must be discussed with the sponsor-investigator on a case by case basis.
- Histologically proven urothelial carcinoma of bladder with predominant transitional cell component. Adenocarcinoma, squamous cell differentiation, or other atypical histology (such as plasmacytoid or sarcomotoid) of the bladder will be allowed on the study, provided they form <50% of the histology
- Females of childbearing potential must have a negative urine and serum pregnancy test within 3 days of study registration.
- NOTE: Female subjects are considered of child bearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are ≥60 years old and naturally postmenopausal for at least 12 consecutive months.
- Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Participation in another clinical study with an investigational product within 2 weeks prior to registration.
- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
- Previous systemic immunotherapy. Previous use of intravesical BCG is acceptable.
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence. However adequately treated prostate cancer >3 years ago with no significant change in PSA for past 6 months can be included. Patients with a history of prostate cancer must not have any definitive radiation therapy to prostate area.
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- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ.
- Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) within14 days prior to the first dose of study drug (14 days prior to the first dose of study drug for subjects who have received prior TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C).
- Mean QT interval corrected for heart rate (QTc) ≥470 ms on electrocardiogram (ECG) using Frediricia's Correction.
- Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, 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.
- Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy. (Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy).
- Any prior Grade ≥3 Immune-mediated adverse event (imAE) while receiving any previous immunotherapy agent, or any unresolved imAE >Grade 1.
- Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. Patients with h/o completely resolved childhood asthma or atopy will not be excluded. Patients with well-controlled hypothyroidism on thyroxine replacement will be eligible as well.
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
- History of and/or confirmed pneumonitis.
- History of primary immunodeficiency.
- History of allogeneic organ transplant.
- History of hypersensitivity to durvalumab or any excipient.
- History of hypersensitivity to the combination or radiation therapy.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
- Known history of previous clinical diagnosis of tuberculosis.
- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of starting treatment with durvalumab.
- Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control. For this study male or female patients of reproductive potential need to employ two highly effective and acceptable forms of contraception throughout their participation in the study and for 90 days after last dose of study drug
- Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
- Brain metastases or history of leptomeningeal carcinomatosis.
- Subjects with uncontrolled seizures.
- Previous definitive radiation to pelvic area.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Penn State Cancer Intsitute
Hershey, Pennsylvania, 17033
University of Iowa Hospital and Clinics
Iowa City, Iowa, 52242
University of Wisconsin
Madison, Wisconsin, 53705
Froedtert & The Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Nebraska Methodist Hospital
Omaha, Nebraska, 68114
Montefiore Medical Center
The Bronx, New York, 10641
About this study
Official title: Phase Ib/II Study of Concurrent Durvalumab And Radiation Therapy (DUART) Followed by Adjuvant Durvalumab in Patients With Urothelial Cancer (T2-4 N0-2 M0) of the Bladder: Big Ten Cancer Research Consortium BTCRC-GU15-023
This is an open label, multi-institutional, single arm study of a phase Ib study, followed by a phase II study of durvalumab with radiation therapy (RT) in patients with urothelial cancer (UC). No randomization or blinding is involved.
Read the detailed description
OUTLINE: This is a multi-center study.
The phase Ib study will evaluate the safety of combining durvalumab with RT followed by adjuvant durvalumab. The phase II study will estimate the Progression Free Survival (PFS) and Disease Control Rate (DCR) with durvalumab plus RT followed by single agent durvalumab for patients with UC of bladder.
PHASE Ib INVESTIGATIONAL TREATMENT:
Cohort 1 will consist of up to 6 patients who will receive durvalumab 1500mg 2 doses Q4 weekly with RT to gross disease, 64.8 Gy, 36 fractions on weekdays over about 7 weeks. Durvalumab will be started on day 1; RT will be started on day 1 or 2.
Three patients will be enrolled initially. If 2 or more patients (out of 3) experience dose-limiting toxicity (DLT), the combined treatment will be considered unsafe. Otherwise, an additional 3 patients will be treated at the same dose. If 0 or 1 patient experience DLT, the dose of durvalumab will be deemed safe for phase 2 part of the study. If, however, 2 or more patients (out of 6) experience DLT, the combined treatment will be considered unsafe.
Post-concurrent durvalumab and RT, single agent durvalumab will be given1500mg every 4 weeks (±7 days) for a total period of up to 12 months. Adjuvant durvalumab treatment will be started 3-4 weeks post completion of durvalumab and RT.
PHASE II INVESTIGATIONAL TREATMENT:
Subjects will receive durvalumab 1500mg 2 doses Q4 weekly with RT to gross disease, 64.8 Gy, 36 fractions on weekdays over about 7 weeks. Durvalumab will start on Day 1. RT to start on Day 1 or 2.
Post-concurrent durvalumab and RT, single agent durvalumab will be given1500mg every 4 weeks (±7 days) for a total period of up to 12 months. Adjuvant durvalumab monotherapy will be started 3-4 weeks post completion of durvalumab and RT.
Life expectancy of >6 months per treating physician.
Adequate organ and marrow function as defined below:
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (> 1500 per mm^3)
- Platelet count ≥ 100 x 10^9/L (>100,000 per mm^3)
- Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
- AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN.
- Serum creatinine CL>30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
- Conditions
- Urothelial Cancer
- Being tested
- durvalumab, Radiation Therapy
- Keywords
- durvalumab, MEDI4736, anti-PD-L1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
durvalumabDrug
1500 mg Q4 weekly
Radiation TherapyRadiation
Also called RT
64.8 Gy, 36 daily fractions on weekdays over about 7 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Safety Run In Phase Ib | Experimental | Subjects will receive durvalumab 1500mg Q4 weekly with RT to gross disease over 36 fractions. Durvalumab will start on Day 1. RT to start on Day 1 or 2. Subjects will receive adjuvant durvalumab monotherapy Q4 week, up to 12 months. Durvalumab monotherapy to start 4 weeks post completion of durvalumab and RT. Receives: Drug: durvalumab; Radiation: Radiation Therapy |
| Arm B: Investigational Treatment Phase II | Experimental | Subjects will receive durvalumab 1500mg Q4 weekly with RT to gross disease over 36 fractions. Durvalumab will start on Day 1. RT to start on Day 1 or 2.. Subjects will receive adjuvant durvalumab monotherapy Q4 week, up to 12 months. Adjuvant durvalumab monotherapy to start 4 weeks post completion of durvalumab and RT. Receives: Drug: durvalumab; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ib: Safety Assessment - Evaluation of DLT (Dose Limiting Toxicity) Rate
To assess the safety of combining durvalumab with RT in that DLT rate is lower than than 33% based on CTCAEv4.0
Measured: Begin W1 and every 2 chemotherapy cycles (2 weeks) thereafter, for up to 2 years or until unacceptable toxicity.
All Phases: Progression Free Survival Rate at 1 Year
Progression free survival rate at one year is defined as the probability that a patient remains free of progression of disease (SD+CR+PR) by modified RECIST 1.1 and cystoscopy at 1 year from the start of durvalumab treatment, D1 of durvaRT.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Measured: From C1D1 to Progression or until death for 1 year
Phase II: Disease Control Rate to Concurrent durvaRT Followed by Durvalumab
The number of all subjects is reported with stable disease (SD) for 8 weeks, or partial response (PR), or complete response (CR) according to modified RECIST 1.1 and cystoscopy, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease(SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started;Disease Control Rate (DCR) = CR + PR+SD
Measured: From C1D1 until death or up to a maximum of 39 months.
Secondary outcomes (4)
All Phases: DCR Post Completion of Concurrent durvaRT
We will be determining the disease control rate, defined as percentage of patients achieving CR, PR, SD post completion of concurrent durvaRT. This will give us some preliminary evidence for efficacy of durvaRT combination.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease(SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started;Disease Control Rate (DCR) = CR + PR+SD
Measured: From C1D1 until death or up to a maximum of 39 months
All Phases : Median Progression Free Survival (PFS) Time
Median progression free survival will be determined for all subjects.
Measured: From C1D1 to PD or until death or up to a maximum of 37 months.
Phase II: Complete Remission
Estimate the rate of CR is one of the secondary objectives for phase II part of this study. This will help us determine the actual effectiveness of durvaRT approach. CR will be determined with the help of imaging and cystoscopy post completion of durvaRT per modified RECIST 1.1.
Number of subjects reporting CR will be reported here. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions.
Measured: From C1D1 until CR or death or up to a maximum of 39 months.
All Phases: Overall Survival
Estimate the overall survival (OS), defined as time from start of treatment, D1, to the date of death due to any cause. OS is defined, as time from start of treatment to the date of death due to any cause, or to the date of censoring at the last time the subject was known to be alive in intention-to-treat population. OS is one of the secondary objectives of this study. This is an immunotherapy based clinical trial and it is prudent to determine the OS to reflect the long-term benefit from this therapeutic approach.
Measured: From C1D1 until death or 39 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2016 (estimated)
- Study start16 Nov 2016
- Primary completion6 Aug 2019
- Study completion27 Apr 2022
Why it stopped: Sponsor-investigator elected to discontinue followup on remaining subjects after planned analyses and manuscripts were completed.
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 Urothelial CancerStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Monika Joshi, MD
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor-investigator, Monika Joshi, MD, Big Ten Cancer Research Consortium
- Investigators
- Monika Joshi, MD, MRCP, Principal investigator, Penn State Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02891161
- Sponsor's protocol ID
- BTCRC-GU15-023
- Acronym
- DUART
- Status last verified
- Nov 2024
- First submitted
- 1 Sep 2016
- Last updated
- 27 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Joshi M, Tuanquin L, Zhu J, Walter V, Schell T, Kaag M, Kilari D, Liao J, Holder SL, Emamekhoo H, Sankin A, Merrill S, Zheng H, Warrick J, Hauke R, Gartrel B, Stein M, Drabick J, Degraff DJ, Zakharia Y. Concurrent durvalumab and radiation therapy (DUART) followed by adjuvant durvalumab in patients with localized urothelial cancer of bladder: results from phase II study, BTCRC-GU15-023. J Immunother Cancer. 2023 Feb;11(2):e006551. doi: 10.1136/jitc-2022-006551.
PubMed 36822667
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib/II Study of Concurrent Durvalumab And Radiation Therapy (DUART) Followed by Adjuvant Durvalumab in Patients With Urothelial Cancer (T2-4 N0-2 M0) of the Bladder: Big Ten Cancer Research Consortium BTCRC-GU15-023
- ClinicalTrials.gov ID
- NCT02891161
- Acronym / sponsor ID
- DUART / BTCRC-GU15-023
- Conditions
- Urothelial Cancer
- Keywords
- durvalumab, MEDI4736, anti-PD-L1
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor-investigator elected to discontinue followup on remaining subjects after planned analyses and manuscripts were completed.
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Monika Joshi, MDUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 16 Nov 2016 (actual)
- Primary completion
- 6 Aug 2019 (actual)
- Study completion
- 27 Apr 2022 (actual)
- First posted
- 7 Sep 2016 (estimated)
- Results
- Posted 27 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label, multi-institutional, single arm study of a phase Ib study, followed by a phase II study of durvalumab with radiation therapy (RT) in patients with urothelial cancer (UC). No randomization or blinding is involved.
Detailed description
OUTLINE: This is a multi-center study.
The phase Ib study will evaluate the safety of combining durvalumab with RT followed by adjuvant durvalumab. The phase II study will estimate the Progression Free Survival (PFS) and Disease Control Rate (DCR) with durvalumab plus RT followed by single agent durvalumab for patients with UC of bladder.
PHASE Ib INVESTIGATIONAL TREATMENT:
Cohort 1 will consist of up to 6 patients who will receive durvalumab 1500mg 2 doses Q4 weekly with RT to gross disease, 64.8 Gy, 36 fractions on weekdays over about 7 weeks. Durvalumab will be started on day 1; RT will be started on day 1 or 2.
Three patients will be enrolled initially. If 2 or more patients (out of 3) experience dose-limiting toxicity (DLT), the combined treatment will be considered unsafe. Otherwise, an additional 3 patients will be treated at the same dose. If 0 or 1 patient experience DLT, the dose of durvalumab will be deemed safe for phase 2 part of the study. If, however, 2 or more patients (out of 6) experience DLT, the combined treatment will be considered unsafe.
Post-concurrent durvalumab and RT, single agent durvalumab will be given1500mg every 4 weeks (±7 days) for a total period of up to 12 months. Adjuvant durvalumab treatment will be started 3-4 weeks post completion of durvalumab and RT.
PHASE II INVESTIGATIONAL TREATMENT:
Subjects will receive durvalumab 1500mg 2 doses Q4 weekly with RT to gross disease, 64.8 Gy, 36 fractions on weekdays over about 7 weeks. Durvalumab will start on Day 1. RT to start on Day 1 or 2.
Post-concurrent durvalumab and RT, single agent durvalumab will be given1500mg every 4 weeks (±7 days) for a total period of up to 12 months. Adjuvant durvalumab monotherapy will be started 3-4 weeks post completion of durvalumab and RT.
Life expectancy of >6 months per treating physician.
Adequate organ and marrow function as defined below:
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (> 1500 per mm^3)
- Platelet count ≥ 100 x 10^9/L (>100,000 per mm^3)
- Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
- AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN.
- Serum creatinine CL>30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Safety Run In Phase Ib | Experimental | Drug: durvalumab, Radiation: Radiation TherapySubjects will receive durvalumab 1500mg Q4 weekly with RT to gross disease over 36 fractions. Durvalumab will start on Day 1. RT to start on Day 1 or 2. Subjects will receive adjuvant durvalumab monotherapy Q4 week, up to 12 months. Durvalumab monotherapy to start 4 weeks post completion of durvalumab and RT. |
| Arm B: Investigational Treatment Phase II | Experimental | Drug: durvalumab, Radiation: Radiation TherapySubjects will receive durvalumab 1500mg Q4 weekly with RT to gross disease over 36 fractions. Durvalumab will start on Day 1. RT to start on Day 1 or 2.. Subjects will receive adjuvant durvalumab monotherapy Q4 week, up to 12 months. Adjuvant durvalumab monotherapy to start 4 weeks post completion of durvalumab and RT. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Locally advanced urothelial cancer of bladder with any of the following:
- Locally advanced urothelial cancer of bladder with any of the following:
- T2, N0, M0 who are ineligible to get cisplatin based chemotherapy.
- Written informed consent and HIPAA authorization for personal health information, obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
Key exclusion criteria (29 listed)
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Participation in another clinical study with an investigational product within 2 weeks prior to registration.
- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
- Previous systemic immunotherapy. Previous use of intravesical BCG is acceptable.
- History of another primary malignancy except for:
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 |
|---|---|---|
| durvalumab1500 mg Q4 weekly | Drug | Arm A: Safety Run In Phase Ib, Arm B: Investigational Treatment Phase II |
| Radiation TherapyAlso: RT64.8 Gy, 36 daily fractions on weekdays over about 7 weeks | Radiation | Arm A: Safety Run In Phase Ib, Arm B: Investigational Treatment Phase II |
Primary outcome
Phase Ib: Safety Assessment - Evaluation of DLT (Dose Limiting Toxicity) Rate
Time frame: Begin W1 and every 2 chemotherapy cycles (2 weeks) thereafter, for up to 2 years or until unacceptable toxicity.
To assess the safety of combining durvalumab with RT in that DLT rate is lower than than 33% based on CTCAEv4.0
All Phases: Progression Free Survival Rate at 1 Year
Time frame: From C1D1 to Progression or until death for 1 year
Progression free survival rate at one year is defined as the probability that a patient remains free of progression of disease (SD+CR+PR) by modified RECIST 1.1 and cystoscopy at 1 year from the start of durvalumab treatment, D1 of durvaRT. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Phase II: Disease Control Rate to Concurrent durvaRT Followed by Durvalumab
Time frame: From C1D1 until death or up to a maximum of 39 months.
The number of all subjects is reported with stable disease (SD) for 8 weeks, or partial response (PR), or complete response (CR) according to modified RECIST 1.1 and cystoscopy, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease(SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started;Disease Control Rate (DCR) = CR + PR+SD
4 secondary outcomes
All Phases: DCR Post Completion of Concurrent durvaRT
Time frame: From C1D1 until death or up to a maximum of 39 months
All Phases : Median Progression Free Survival (PFS) Time
Time frame: From C1D1 to PD or until death or up to a maximum of 37 months.
Phase II: Complete Remission
Time frame: From C1D1 until CR or death or up to a maximum of 39 months.
All Phases: Overall Survival
Time frame: From C1D1 until death or 39 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36822667Joshi M, Tuanquin L, Zhu J, Walter V, Schell T, Kaag M, Kilari D, Liao J, Holder SL, Emamekhoo H, Sankin A, Merrill S, Zheng H, Warrick J, Hauke R, Gartrel B, Stein M, Drabick J, Degraff DJ, Zakharia Y. Concurrent durvalumab and radiation therapy (DUART) followed by adjuvant durvalumab in patients with localized urothelial cancer of bladder: results from phase II study, BTCRC-GU15-023. J Immunother Cancer. 2023 Feb;11(2):e006551. doi: 10.1136/jitc-2022-006551.
- Big Ten Cancer Research Consortium 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.
Monika Joshi, MD, MRCP principal investigator
Penn State Cancer Institute
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing durvalumab and Radiation Therapy in people with Urothelial Cancer, run by Monika Joshi, MD at 7 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 18 inclusion and 29 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 27 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 27 Nov 2024). 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?
Phase Ib: Safety Assessment - Evaluation of DLT (Dose Limiting Toxicity) Rate (time frame: Begin W1 and every 2 chemotherapy cycles (2 weeks) thereafter, for up to 2 years or until unacceptable toxicity.). The study lists 3 primary outcomes in all. 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 NCT02891161, 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 27 Nov 2024.