Clinical Trials /

Vactosertib With Durvalumab in Urothelial Carcinoma Failing Checkpoint Inhibition

NCT04064190

Description:

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

Related Conditions:
  • Bladder Urothelial Carcinoma
  • Renal Pelvis and Ureter Urothelial Carcinoma
  • Urethral Urothelial Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: MP-VAC-202 (ION-03)
  • NCT ID: NCT04064190

Conditions

  • Urothelial Carcinoma Recurrent
  • Advanced Urothelial Carcinoma

Interventions

DrugSynonymsArms
Vactosertib(TEW-7197)/ DurvalumabVactosertib+Durvalumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Vactosertib+DurvalumabExperimentalVactosertib will be administered in combination with standard dose of durvalumab every four weeks.
  • Vactosertib(TEW-7197)/ Durvalumab

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:12months
Safety Issue:
Description:ORR by RECIST version 1.1

Secondary Outcome Measures

Measure:Time to Tumor Response
Time Frame:Overall study period up to 3years
Safety Issue:
Description:TTR by RECIST version 1.1 and iRECIST
Measure:Best Response
Time Frame:Overall study period up to 3years
Safety Issue:
Description:Best response (percent of tumor shrinkage) by RECIST version 1.1 and iRECIST
Measure:Duration of Response
Time Frame:Overall study period up to 3years
Safety Issue:
Description:DoR by RECIST version 1.1 and iRECIST
Measure:Progression Free Survival
Time Frame:6-month/ 12-month
Safety Issue:
Description:PFS by RECIST version 1.1 and iRECIST
Measure:Overall survival
Time Frame:12month
Safety Issue:
Description:OS by RECIST version 1.1 and iRECIST
Measure:Tumor-specific immune responses
Time Frame:Overall study period up to 3years
Safety Issue:
Description: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
Measure:Incidence of Treatment-Emergent Adverse Events [Safety and tolerability]
Time Frame:Overall study period up to 3years
Safety Issue:
Description:To assess safety and tolerability of vactosertib administered concurrent with Durvalumab in patients with urothelial carcinoma failing checkpoint inhibition

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:MedPacto, Inc.

Last Updated

September 7, 2020