Advanced Urothelial Carcinoma, Urothelial Carcinoma Recurrent
Conditions
Brief summary
This is Phase 2, open label, non randomized single arm study to determine whether the administration of vactosertib with durvalumab will provide meaningful increases in the Overall Response Rate (ORR) in patients with urothelial cancers that fail to achieve a response with anti-PD-1/PD-L1 based regimens
Detailed description
This is a Phase 2, open-label, non-randomized, two-cohort multi center study with a safety run-in of 6 patients in Cohort 1. It is anticipated that a total of 48 patients will be enrolled. Durvalumab will be administered with the standard regimen of 1500 mg intravenously (IV) every four weeks. Vactosertib will be administered at a dose of 300 mg PO BID for 5 days per week All treatment will be administered up to two years and the trial is anticipated to be completed over a period of 36 months.
Interventions
DRUGVactosertib(TEW-7197)/ Durvalumab
Vactosertib (PO) in combination with Durvalumab (IV) every 4 weeks
Sponsors
AstraZeneca
MedPacto, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 2, open label, non randomized single arm study with two cohorts and a safety run-in for first six patients
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrollment 2. Histologically or cytologically documented locally advanced/inoperable or metastatic urothelial bladder carcinoma (UBC), including renal pelvis, ureters, urinary bladder, and urethra. 3. Prior anti-PD-(L)1 treatment. 4. Measurable disease per RECIST 1.1 assessed by computed tomography (CT) scan or MRI. 5. Recurrent disease after any prior platinum-based chemotherapy regimen or ineligible for platinum therapy. 6. Adequate organ and marrow function as defined 7. Must have a life expectancy of at least 12 weeks. 8. Body weight \> 30 kg
Exclusion criteria
1. History of allogeneic organ transplantation. 2. Active or prior documented autoimmune or inflammatory disorders 3. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure . 4. History of another primary malignancy 5. History of leptomeningeal carcinomatosis. 6. History of active primary immunodeficiency. 7. Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen \[HBsAg\] result), hepatitis C, or human immunodeficiency virus . 8. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 12months | ORR by RECIST version 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Tumor Response | Overall study period up to 3years | TTR by RECIST version 1.1 and iRECIST |
| Best Response | Overall study period up to 3years | Best response (percent of tumor shrinkage) by RECIST version 1.1 and iRECIST |
| Duration of Response | Overall study period up to 3years | DoR by RECIST version 1.1 and iRECIST |
| Incidence of Treatment-Emergent Adverse Events [Safety and tolerability] | Overall study period up to 3years | To assess safety and tolerability of vactosertib administered concurrent with Durvalumab in patients with urothelial carcinoma failing checkpoint inhibition |
| Overall survival | 12month | OS by RECIST version 1.1 and iRECIST |
| Tumor-specific immune responses | Overall study period up to 3years | tumor-specific immune responses within on-therapy biopsies measured by increased T cell infiltration and increased IFN-λ signature. and the correlation with outcome as measured by ORR, TTR, DoR, PFS and OS |
| Progression Free Survival | 6-month/ 12-month | PFS by RECIST version 1.1 and iRECIST |
Countries
United States
Outcome results
None listed