A prospective, multi-center, open-label, single-arm, two- step phase II study of DURvalumab (MEDI4736) in patients WIth poor performance status as first-liNe treatment for advanced urothelial cancer: the DURWIN trial
- Conditions
- Patients aged 18 years or older with histologically or cytologically documented locally advanced (on the TNM staging system, T4b and any Nor any T and N2–3) or metastatic (M1, stage IV) urothelial carcinoma (including of the renal pelvis, ureter, urinary bladder, or urethra) who are eligibile to receive first-line systemic treatment and are judged to be ineligible for cisplatin treatment because of ECOG performance status= 2MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003027-11-IT
- Lead Sponsor
- CONSORZIO ONCOTECH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 48
1. Capable of giving signed informed consent which includes compliance with
the requirements and restrictions listed in the informed consent form (ICF) and
in this protocol. Written informed consent and any locally required
authorization obtained from the patient/legal representative prior to
performing any protocol-related procedures, including screening evaluations;
2. Patients are eligible for enrolment if they have histologically or cytologically
documented locally advanced (on the TNM staging system, T4b and any N; or
any T and N2–3) or metastatic (M1, stage IV) urothelial carcinoma (including
of the renal pelvis, ureter, urinary bladder, or urethra) who are eligibile to
receive first-line systemic treatment and are judged to be ineligible for
cisplatin treatment because of ECOG performance status= 2;
3. Age > 18 years at time of study entry;
4. All patients must have measurable disease defined by Response Evaluation
Criteria In Solid Tumors version 1.1 (RECIST v1.1);
5. Eastern Cooperative Oncology Group (ECOG) performance status of 2;
6. Life expectancy of > 12 weeks;
7. Body weight >30kg;
8. Adequate normal organ and marrow function
9. Evidence of post-menopausal status or negative urinary or serum pregnancy
test for female pre-menopausal patients. Women will be considered postmenopausal
if they have been amenorrheic for 12 months without an
alternative medical cause
10. Patient 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24
1. Participation in another clinical study with an investigational product during
the last 28 days,
2. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study,
3. Any prior systemic anticancer therapy received against urothelial carcinoma, with the exception of neoadjuvant or adjuvant chemotherapy if the last dose was administered > 12 months before study inclusion,
4. Any previous treatment with a PD-1 or PD-L1 inhibitor, including
durvalumab,
5. History of another primary malignancy
6. Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3
electrocardiograms (ECGs) using Fridericia’s Correction,
7. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer
therapy with the exception of alopecia, vitiligo, and the laboratory values
defined in the inclusion criteria,
8. Any concurrent chemotherapy, Investigational Product (IP), biologic, or hormonal therapy for cancer treatment.
9. Radiotherapy treatment to more than 30% of the bone marrow or with a wide
field of radiation within 4 weeks of the first dose of study drug,
10. Major surgical procedure (as defined by the Investigator) within 28 days prior
to the first dose of IP. Local surgery of isolated lesions for palliative intent is
acceptable,
11. History of allogenic organ transplantation,
12. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis
[with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with
polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]).
13. Uncontrolled intercurrent illness,
14. History of leptomeningeal carcinomatosis,
15. Brain metastases or spinal cord compression. Patients with suspected brain
metastases at screening should have an MRI (preferred) or CT each preferably
with IV contrast of the brain prior to study entry,
16. History of active primary immunodeficiency,
17. Active infection including tuberculosis (clinical evaluation that includes
clinical history, physical examination and radiographic findings, and TB
testing in line with local practice), hepatitis B (known positive HBV surface
antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus
(positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection
(defined as the presence of hepatitis B core antibody [anti-HBc] and absence
of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are
eligible only if polymerase chain reaction is negative for HCV RNA.
18. Current or prior use of immunosuppressive medication within 14 days before
the first dose of durvalumab.
19. 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,
20. Female patients who are pregnant or breastfeeding or male or female patients
of reproductive potential who are not willing to employ effective birth control
from screening to 90 days after the last dose of durvalumab,
21. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients,
22. Patients with ECOG performance status of 0-1 -3-4 must be excluded.
23. Judgment by the investigator that the patient is unsuitab
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is to assess the overall response rate as evaluated according to RECIST 1.1 criteria;Secondary Objective: Secondary objectives are to assess the following:<br>a) Overall response rate according to iRECIST criteria<br>b) Progression free survival according to RECIST 1.1 criteria<br>c) Progression free survival according to iRECIST criteria<br>d) Safety<br>e) Overall survival<br>f) Duration of radiological response<br>g) Overall survival rate % after 6 months<br>h) Quality of life as determined according to the FACT-Bladder questionnaire v4;Primary end point(s): Radiological response rate according to RECIST 1.1 criteria among all evaluable patients.;Timepoint(s) of evaluation of this end point: Patients will have scans done every 8 weeks for the first 24 weeks, and then every 12 weeks thereafter (relative to the date of inclusion) until confirmed PD.
- Secondary Outcome Measures
Name Time Method