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

NCT ID: NCT02401542

Last Updated: 2020-03-09

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

71 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-06-30

Study Completion Date

2019-11-01

Brief Summary

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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).

Detailed Description

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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).

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Vofatamab plus docetaxel

IV infusion of docetaxel, 75 mg/m2, followed by IV infusion of vofatamab, 25 mg/kg, on day one of each 21-day cycle. One additional IV infusion of vofatamab (25 mg/kg) given on Day 8 of Cycle 1.

Dosing with vofatamab and docetaxel will continue in each patient until disease progression, unacceptable toxicity, death, or study exit, including withdrawal of patient consent or study termination. Docetaxel treatment beyond 12 cycles of therapy may be considered at the discretion of the treating investigator and Medical Monitor.

Group Type ACTIVE_COMPARATOR

Vofatamab

Intervention Type DRUG

Docetaxel

Intervention Type DRUG

Placebo plus docetaxel

IV infusion of docetaxel, 75 mg/m2, followed by IV infusion of placebo on day one of each 21-day cycle.

One additional IV infusion of placebo given on Day 8 of Cycle 1. Dosing of docetaxel and placebo will continue in each patient until disease progression, unacceptable toxicity, death, or study exit, including withdrawal of patient consent or study termination. Docetaxel treatment beyond 12 cycles of therapy may be considered at the discretion of the treating investigator and Medical Monitor

Group Type PLACEBO_COMPARATOR

Docetaxel

Intervention Type DRUG

Placebo

Intervention Type DRUG

Vofatamab

IV infusion vofatamab, 25 mg/kg on day one each 21-day cycle. One additional IV infusion of vofatamab (25 mg/kg) given on Day 8 of Cycle 1.

Dosing of vofatamab will continue in each patient until disease progression, unacceptable toxicity, death, or study exit, including withdrawal of patient consent or study termination.

Group Type EXPERIMENTAL

Vofatamab

Intervention Type DRUG

Interventions

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Vofatamab

Intervention Type DRUG

Docetaxel

Intervention Type DRUG

Placebo

Intervention Type DRUG

Other Intervention Names

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B-701 MFGR1877S R3Mab Docefrez Taxotere

Eligibility Criteria

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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)


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.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rainier Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rainier Therapeutics

Role: STUDY_CHAIR

Rainier Therapeutics

Locations

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Research Site

Gilbert, Arizona, United States

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Goodyear, Arizona, United States

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Duarte, California, United States

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Miami, Florida, United States

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Fort Wayne, Indiana, United States

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Louisville, Kentucky, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Rochester, Minnesota, United States

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Syracuse, New York, United States

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Dallas, Texas, United States

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Olomouc, , Czechia

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Prague, , Czechia

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Ancona, , Italy

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Catania, , Italy

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Milan, , Italy

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Milan, , Italy

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Milan, , Italy

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Modena, , Italy

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Napoli, , Italy

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Negrar, , Italy

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Siena, , Italy

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Gwangju, , South Korea

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Incheon, , South Korea

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Seongnam-si, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Badalona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Granada, , Spain

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Lugo, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Oviedo, , Spain

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Pamplona, , Spain

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Valencia, , Spain

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Vigo, , Spain

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Uppsala, , Sweden

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Kaohsiung City, , Taiwan

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Taichung, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Adana, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Antalya, , Turkey (Türkiye)

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Bursa, , Turkey (Türkiye)

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Edirne, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Malatya, , Turkey (Türkiye)

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London, , United Kingdom

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Preston, , United Kingdom

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Countries

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United States Czechia Italy South Korea Spain Sweden Taiwan Turkey (Türkiye) United Kingdom

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2017-001319-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

B-701-U21

Identifier Type: -

Identifier Source: org_study_id

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