Ignite Creation Date:
2025-12-25 @ 12:40 AM
Ignite Modification Date:
2025-12-25 @ 10:50 PM
Study NCT ID:
NCT04628767
Status:
RECRUITING
Last Update Posted:
2025-12-24
First Post:
2020-11-13
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Testing the Addition of MEDI4736 (Durvalumab) to Chemotherapy Before Surgery for Patients With High-Grade Upper Urinary Tract Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase II/III Trial of Durvalumab and Chemotherapy for Patients With High Grade Upper Tract Urothelial Cancer Prior to Nephroureterectomy
Status:
RECRUITING
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II/III trial compares the effect of adding durvalumab to chemotherapy versus chemotherapy alone before surgery in treating patients with upper urinary tract cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as methotrexate, vinblastine, doxorubicin, cisplatin, and gemcitabine work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Durvalumab in combination with chemotherapy before surgery may enhance the shrinking of the tumor compared to chemotherapy alone.
Detailed Description:
PRIMARY OBJECTIVES:
I. To compare event-free survival (EFS) between patients with upper tract urothelial cancer (UTUC) randomized to neoadjuvant accelerated methotrexate, vinblastine, adriamycin, cisplatin (aMVAC) alone or in combination with durvalumab. (Cisplatin eligible patients \[Arms A and B\]) II. Evaluation of pathologic complete response at radical nephroureterectomy (RNU) (pathologic complete response \[pCR\], ypT0N0/ Nx). (Cisplatin ineligible patients \[Arm C\]).
SECONDARY OBJECTIVES:
I. To assess pathologic complete response (pCR) at surgery. (Cisplatin eligible cohort) II. Event-free survival (EFS) will be evaluated for the cisplatin ineligible cohort as a secondary endpoint. (Cisplatin ineligible cohort) III. Overall survival in all, and by post chemotherapy response (ypt0N0, yp =\< T1N0, yp \>= T2Nany). (All patients) IV. To evaluate disease-free survival (DFS) in each arm of the trial separately. (All patients) V. To evaluate cancer-specific survival of patients in each arm of the trial separately. (All patients) VI. To evaluate renal function outcomes following systemic treatment and following surgery (\[RNU) in each arm of the trial separately. (All patients) VII. To evaluate safety and tolerability of neoadjuvant aMVAC alone or in combination with durvalumab prior to RNU. (All patients)
OUTLINE: Patients eligible for cisplatin are randomized to Arms A or B. Patients ineligible for cisplatin are assigned to Arm C.
ARM A: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of chemotherapy cycles 1 and 3. Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.
ARM B: Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.
ARM C: Patients receive durvalumab IV over 60 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.
Patients also undergo tissue biopsy and blood sample collection on study, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial.
After completion of study treatment, patients are followed up within 30 days and then every 3-6 months for up to 5 years from study entry.
I. To compare event-free survival (EFS) between patients with upper tract urothelial cancer (UTUC) randomized to neoadjuvant accelerated methotrexate, vinblastine, adriamycin, cisplatin (aMVAC) alone or in combination with durvalumab. (Cisplatin eligible patients \[Arms A and B\]) II. Evaluation of pathologic complete response at radical nephroureterectomy (RNU) (pathologic complete response \[pCR\], ypT0N0/ Nx). (Cisplatin ineligible patients \[Arm C\]).
SECONDARY OBJECTIVES:
I. To assess pathologic complete response (pCR) at surgery. (Cisplatin eligible cohort) II. Event-free survival (EFS) will be evaluated for the cisplatin ineligible cohort as a secondary endpoint. (Cisplatin ineligible cohort) III. Overall survival in all, and by post chemotherapy response (ypt0N0, yp =\< T1N0, yp \>= T2Nany). (All patients) IV. To evaluate disease-free survival (DFS) in each arm of the trial separately. (All patients) V. To evaluate cancer-specific survival of patients in each arm of the trial separately. (All patients) VI. To evaluate renal function outcomes following systemic treatment and following surgery (\[RNU) in each arm of the trial separately. (All patients) VII. To evaluate safety and tolerability of neoadjuvant aMVAC alone or in combination with durvalumab prior to RNU. (All patients)
OUTLINE: Patients eligible for cisplatin are randomized to Arms A or B. Patients ineligible for cisplatin are assigned to Arm C.
ARM A: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of chemotherapy cycles 1 and 3. Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.
ARM B: Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.
ARM C: Patients receive durvalumab IV over 60 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.
Patients also undergo tissue biopsy and blood sample collection on study, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial.
After completion of study treatment, patients are followed up within 30 days and then every 3-6 months for up to 5 years from study entry.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2020-09850 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| EA8192 | OTHER | ECOG-ACRIN Cancer Research Group | View | |
| EA8192 | OTHER | CTEP | View | |
| U10CA180820 | NIH | None | https://reporter.nih.gov/quic… | View |