Dose Escalation, Expansion Study of Vofatamab (B-701) in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma

Locally Advanced or Metastatic Urothelial Cell Carcinoma Clinical Trial

— FIERCE-21  

Official title:

A Dose Escalation, Expansion Study of Vofatamab (B-701) Alone, Plus Docetaxel, or Versus Docetaxel in Subjects With Locally Advanced or Metastatic Urothelial Cell Carcinoma Who Have Relapsed After, or Are Refractory to Standard Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02401542
• Other study ID #: B-701-U21
• Secondary ID: 2017-001319-36
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 2015
• Est. completion date: November 1, 2019

Study information

• Verified date: February 2020
• Source: Rainier Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1/2(b), sequential, dose escalation, open-label, randomized expansion, multicenter, efficacy and safety study of vofatamab alone or in combination with docetaxel, or versus docetaxel in FGFR3 mutant/fusion subjects with Stage IV, locally advanced or metastatic UCC who have relapsed after, or are refractory to at least one prior line of chemotherapy. This study is divided into 3 phases: Phase 1b (Cohort 1), Phase 2 (Cohorts 2 and 3), and Phase 2b (Monotherapy Expansion Phase and Randomized Phase).

Description:

This is a Phase 1/2(b), sequential, dose escalation, open-label, randomized expansion, multicenter, efficacy and safety study of vofatamab alone or in combination with docetaxel, or versus docetaxel in FGFR3 mutant/fusion subjects with Stage IV, locally advanced or metastatic UCC who have relapsed after, or are refractory to at least one prior line of chemotherapy. Vofatamab is a novel monoclonal antibody specific for fibroblast growth factor receptor 3 (FGFR3) that is being developed to target FGFR3-positive tumors.

This study is divided into 3 phases: Phase 1b (Cohort 1), Phase 2 (Cohorts 2 and 3), and Phase 2b (Monotherapy Expansion Phase and Randomized Phase).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 71
• Est. completion date: November 1, 2019
• Est. primary completion date: November 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Disease Specific Inclusion Criteria:

1. Stage IV, locally advanced or metastatic (T4b, any N; or any T, N2-3) urothelial bladder cancer or TCC arising in another location of the urinary tract, including urethra, ureter, and renal pelvis

2. Histological or cytological diagnosis of UCC.

3. Relapsed after or are refractory to at least one prior line of chemotherapy which has not included a taxane (with the exception of Cohort 3 of Phase 2 and Phase 2b Monotherapy Expansion of Phase 2b which will allow the enrollment of patients with prior treatment with a taxane)

4. Subjects must have received at least one prior chemotherapeutic regimen (at least one cycle each) for advanced or metastatic/recurrent disease, of which at least one regimen included a platinum agent (unless contraindicated).

5. Prior neoadjuvant or adjuvant chemotherapy (without a taxane, except Cohort 3 of Phase 2 and Phase 2b Monotherapy Expansion, which will allow the enrollment of subjects with prior treatment with a taxane) is permitted and will not be counted as first-line chemotherapy, as long as the subject has not progressed within 12 months of the last dose.

6. Measurable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Phase 2 and Phase 2b Specific Inclusion Criteria:

1. Patient must be confirmed to have a FGFR3 genomic alteration at the time of documentation of advanced disease.

2. Relapsed after or are refractory to an immune checkpoint inhibitor. This inclusion criterion does not apply if the checkpoint inhibitor is contraindicated.

Main Exclusion Criteria:

• Prior anti-cancer therapy within 2 weeks prior to Cycle 1, Day 1

• Prior treatment with an inhibitor that is targeted primarily to FGFRs

• Clinically significant comorbid medical conditions or lab abnormalities

• History of major bleeding (requiring a blood transfusion = 2 units) not related to a tumor within the past 12 months

• History of clinically significant coagulation or platelet disorder in the past 12 months

• Currently receiving anticoagulation treatment

• Incomplete healing from wounds from prior surgery

• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at screening

• Presence of positive test results for Hepatitis B or Hepatitis C

• Known history of human immunodeficiency virus (HIV) seropositive status

Related Conditions & MeSH terms

• Carcinoma
• Locally Advanced or Metastatic Urothelial Cell Carcinoma
• Urinary Bladder Disease
• Urinary Bladder Diseases
• Urologic Diseases
• Urological Diseases

Intervention

Drug:
• Vofatamab

• Docetaxel

• Placebo

Locations

Country	Name	City	State
Czechia	Research Site	Olomouc
Czechia	Research Site	Prague
Italy	Research Site	Ancona
Italy	Research Site	Catania
Italy	Research Site	Milan
Italy	Research Site	Milan
Italy	Research Site	Milan
Italy	Research Site	Modena
Italy	Research Site	Napoli
Italy	Research Site	Negrar
Italy	Research Site	Siena
Korea, Republic of	Research Site	Gwangju
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Spain	Research Site	Badalona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Granada
Spain	Research Site	Lugo
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Oviedo
Spain	Research Site	Pamplona
Spain	Research Site	Valencia
Spain	Research Site	Vigo
Sweden	Research Site	Uppsala
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Antalya
Turkey	Research Site	Bursa
Turkey	Research Site	Edirne
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Malatya
United Kingdom	Research Site	London
United Kingdom	Research Site	Preston
United States	Research Site	Boston	Massachusetts
United States	Research Site	Dallas	Texas
United States	Research Site	Detroit	Michigan
United States	Research Site	Duarte	California
United States	Reaserach Site	Fort Wayne	Indiana
United States	Research Site	Gilbert	Arizona
United States	Research Site	Goodyear	Arizona
United States	Research Site	Louisville	Kentucky
United States	Research Site	Miami	Florida
United States	Research Site	Rochester	Minnesota
United States	Research Site	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Rainier Therapeutics

Countries where clinical trial is conducted

United States,  Czechia,  Italy,  Korea, Republic of,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Efficacy Outcome: Progression Free Survival (PFS)	Efficacy of vofatamab plus docetaxel, compared with docetaxel plus placebo, and vofatamab alone as measured by PFS; measured from randomization to first occurrence of disease progression (per RECIST v1.1) or death, whichever occurs first. A patient has had to receive at least one vofatamab dose. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	3-4 years