Back to results

Vactosertib With Durvalumab in Urothelial Carcinoma Failing Checkpoint Inhibition

Primary Purpose

Urothelial Carcinoma Recurrent, Advanced Urothelial Carcinoma

Status

Not yet recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Vactosertib(TEW-7197)/ Durvalumab

About this trial

This is an interventional treatment trial for Urothelial Carcinoma Recurrent

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrollment
Histologically or cytologically documented locally advanced/inoperable or metastatic urothelial bladder carcinoma (UBC), including renal pelvis, ureters, urinary bladder, and urethra.
Prior anti-PD-(L)1 treatment.
Measurable disease per RECIST 1.1 assessed by computed tomography (CT) scan or MRI.
Recurrent disease after any prior platinum-based chemotherapy regimen or ineligible for platinum therapy.
Adequate organ and marrow function as defined
Must have a life expectancy of at least 12 weeks.
Body weight > 30 kg

Exclusion Criteria:

History of allogeneic organ transplantation.
Active or prior documented autoimmune or inflammatory disorders
Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure .
History of another primary malignancy
History of leptomeningeal carcinomatosis.
History of active primary immunodeficiency.
Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus .
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

Sites / Locations

University of California San Francisco
Roswell Park Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vactosertib+Durvalumab

Arm Description

Vactosertib will be administered in combination with standard dose of durvalumab every four weeks.

Outcomes

Primary Outcome Measures

Overall Response Rate

ORR by RECIST version 1.1

Secondary Outcome Measures

Time to Tumor Response

TTR by RECIST version 1.1 and iRECIST

Best Response

Best response (percent of tumor shrinkage) by RECIST version 1.1 and iRECIST

Duration of Response

DoR by RECIST version 1.1 and iRECIST

Progression Free Survival

PFS by RECIST version 1.1 and iRECIST

Overall survival

OS by RECIST version 1.1 and iRECIST

Tumor-specific immune responses

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

Incidence of Treatment-Emergent Adverse Events [Safety and tolerability]

To assess safety and tolerability of vactosertib administered concurrent with Durvalumab in patients with urothelial carcinoma failing checkpoint inhibition

Full Information

NCT ID

NCT04064190

First Posted

August 15, 2019

Last Updated

September 22, 2021

Sponsor

MedPacto, Inc.

Collaborators

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT04064190

Brief Title

Vactosertib With Durvalumab in Urothelial Carcinoma Failing Checkpoint Inhibition

Official Title

A Phase 2 Study of TGF-β Inhibition (Vactosertib) With Anti-PD-L1 (Durvalumab) in Patients With Advanced or Recurrent Urothelial Carcinoma Failing to Achieve Response With Checkpoint Inhibition

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Not yet recruiting

Study Start Date

October 15, 2021 (Anticipated)

Primary Completion Date

December 30, 2023 (Anticipated)

Study Completion Date

December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

MedPacto, Inc.

Collaborators

AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Urothelial Carcinoma Recurrent, Advanced Urothelial Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Phase 2, open label, non randomized single arm study with two cohorts and a safety run-in for first six patients

Masking

None (Open Label)

Allocation

N/A

Enrollment

48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Vactosertib+Durvalumab

Arm Type

Experimental

Arm Description

Vactosertib will be administered in combination with standard dose of durvalumab every four weeks.

Intervention Type

Drug

Intervention Name(s)

Vactosertib(TEW-7197)/ Durvalumab

Intervention Description

Vactosertib (PO) in combination with Durvalumab (IV) every 4 weeks

Primary Outcome Measure Information:

Title

Overall Response Rate

Description

ORR by RECIST version 1.1

Time Frame

12months

Secondary Outcome Measure Information:

Title

Time to Tumor Response

Description

TTR by RECIST version 1.1 and iRECIST

Time Frame

Overall study period up to 3years

Title

Best Response

Description

Best response (percent of tumor shrinkage) by RECIST version 1.1 and iRECIST

Time Frame

Overall study period up to 3years

Title

Duration of Response

Description

DoR by RECIST version 1.1 and iRECIST

Time Frame

Overall study period up to 3years

Title

Progression Free Survival

Description

PFS by RECIST version 1.1 and iRECIST

Time Frame

6-month/ 12-month

Title

Overall survival

Description

OS by RECIST version 1.1 and iRECIST

Time Frame

12month

Title

Tumor-specific immune responses

Description

Time Frame

Overall study period up to 3years

Title

Incidence of Treatment-Emergent Adverse Events [Safety and tolerability]

Description

To assess safety and tolerability of vactosertib administered concurrent with Durvalumab in patients with urothelial carcinoma failing checkpoint inhibition

Time Frame

Overall study period up to 3years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrollment Histologically or cytologically documented locally advanced/inoperable or metastatic urothelial bladder carcinoma (UBC), including renal pelvis, ureters, urinary bladder, and urethra. Prior anti-PD-(L)1 treatment. Measurable disease per RECIST 1.1 assessed by computed tomography (CT) scan or MRI. Recurrent disease after any prior platinum-based chemotherapy regimen or ineligible for platinum therapy. Adequate organ and marrow function as defined Must have a life expectancy of at least 12 weeks. Body weight > 30 kg Exclusion Criteria: History of allogeneic organ transplantation. Active or prior documented autoimmune or inflammatory disorders Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure . History of another primary malignancy History of leptomeningeal carcinomatosis. History of active primary immunodeficiency. Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus . 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sunjin Hwang, MD

Phone

+82 2 6938 0206

sunjin.hwang@medpacto.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lawrence Fong, MD

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94158

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Larry Fong, Dr

Facility Name

Roswell Park Comprehensive Cancer Center

City

Buffalo

State/Province

New York

ZIP/Postal Code

14263

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Gurkamal Chatta, Dr.

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Vactosertib With Durvalumab in Urothelial Carcinoma Failing Checkpoint Inhibition

We'll reach out to this number within 24 hrs