Clinical trial NCT04064190: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Urothelial Carcinoma Recurrent
Advanced Urothelial Carcinoma
Lead sponsor: MedPacto, Inc.
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2019-08-21
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase 2, open label, non randomized single arm study with two cohorts and a safety run-in for first six patients
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Response Rate
timeFrame: 12months
Secondary outcomes:
measure: Time to Tumor Response
timeFrame: Overall study period up to 3years
measure: Best Response
timeFrame: Overall study period up to 3years
measure: Duration of Response
timeFrame: Overall study period up to 3years
measure: Progression Free Survival
timeFrame: 6-month/ 12-month
measure: Overall survival
timeFrame: 12month
measure: Tumor-specific immune responses
timeFrame: Overall study period up to 3years
measure: Incidence of Treatment-Emergent Adverse Events [Safety and tolerability]
timeFrame: Overall study period up to 3years
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
Study officials:
affiliation: University of California, San Francisco
name: Lawrence Fong, MD
role: PRINCIPAL_INVESTIGATOR
References: