NCT02401542

Brief 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).

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
71

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jun 2015

Longer than P75 for phase_1

Geographic Reach
9 countries

65 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 16, 2015

Completed
14 days until next milestone

First Posted

Study publicly available on registry

March 30, 2015

Completed
2 months until next milestone

Study Start

First participant enrolled

June 1, 2015

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2019

Completed
4 months until next milestone

Results Posted

Study results publicly available

February 17, 2020

Completed
Last Updated

March 9, 2020

Status Verified

February 1, 2020

Enrollment Period

4.4 years

First QC Date

March 16, 2015

Results QC Date

February 3, 2020

Last Update Submit

February 14, 2020

Conditions

Keywords

Urothelial Cell CarcinomaUCCbladder cancervofatamabFGFR3invasive bladder cancertargeted therapyTransitional Cell CarcinomaTCCPhase 2second line therapymonoclonal antibodydocetaxelcombination therapyPhase 1monotherapyB-701

Outcome Measures

Primary Outcomes (1)

  • 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

Study Arms (3)

Vofatamab plus docetaxel

ACTIVE COMPARATOR

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.

Drug: VofatamabDrug: Docetaxel

Placebo plus docetaxel

PLACEBO COMPARATOR

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

Drug: DocetaxelDrug: Placebo

Vofatamab

EXPERIMENTAL

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.

Drug: Vofatamab

Interventions

Also known as: B-701, MFGR1877S, R3Mab
VofatamabVofatamab plus docetaxel
Also known as: Docefrez, Taxotere
Placebo plus docetaxelVofatamab plus docetaxel
Placebo plus docetaxel

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • Histological or cytological diagnosis of UCC.
  • 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)
  • 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).
  • 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.
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
  • Patient must be confirmed to have a FGFR3 genomic alteration at the time of documentation of advanced disease.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (65)

Research Site

Gilbert, Arizona, 85234, United States

Location

Research Site

Goodyear, Arizona, 85338, United States

Location

Research Site

Duarte, California, 91010, United States

Location

Research Site

Miami, Florida, 33140, United States

Location

Reaserach Site

Fort Wayne, Indiana, 46845, United States

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Research Site

Louisville, Kentucky, 40202, United States

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Research Site

Boston, Massachusetts, 02215, United States

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Research Site

Detroit, Michigan, 48201, United States

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Research Site

Rochester, Minnesota, 55905, United States

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Research Site

Syracuse, New York, 13210, United States

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Research Site

Dallas, Texas, 75390-9110, United States

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Research Site

Olomouc, 77900, Czechia

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Research Site

Prague, 12808, Czechia

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Research Site

Ancona, 60126, Italy

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Research Site

Catania, 95123, Italy

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Research Site

Milan, 20132, Italy

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Research Site

Milan, 20133, Italy

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Research Site

Milan, 20141, Italy

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Research Site

Modena, 41124, Italy

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Research Site

Napoli, 80131, Italy

Location

Research Site

Negrar, 37024, Italy

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Research Site

Siena, 53100, Italy

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Research Site

Gwangju, 61469, South Korea

Location

Research Site

Incheon, 405-760, South Korea

Location

Research Site

Seongnam-si, 13620, South Korea

Location

Research Site

Seoul, 02841, South Korea

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 03722, South Korea

Location

Research Site

Seoul, 05505, South Korea

Location

Research Site

Seoul, 06351, South Korea

Location

Research Site

Badalona, 08916, Spain

Location

Research Site

Barcelona, 08003, Spain

Location

Research Site

Barcelona, 08026, Spain

Location

Research Site

Barcelona, 08036, Spain

Location

Research Site

Barcelona, 08908, Spain

Location

Research Site

Granada, 18014, Spain

Location

Research Site

Lugo, 27003, Spain

Location

Research Site

Madrid, 28007, Spain

Location

Research Site

Madrid, 28033, Spain

Location

Research Site

Madrid, 28041, Spain

Location

Research Site

Madrid, 28046, Spain

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Research Site

Madrid, 28050, Spain

Location

Research Site

Oviedo, 33011, Spain

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Research Site

Pamplona, 31008, Spain

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Research Site

Valencia, 46009, Spain

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Research Site

Vigo, 36204, Spain

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Research Site

Uppsala, 751 85, Sweden

Location

Research Site

Kaohsiung City, 81362, Taiwan

Location

Research Site

Kaohsiung City, 83301, Taiwan

Location

Research Site

Taichung, 40447, Taiwan

Location

Research Site

Taichung, 435, Taiwan

Location

Research Site

Tainan, 704, Taiwan

Location

Research Site

Taipei, 110, Taiwan

Location

Research Site

Taipei, 11217, Taiwan

Location

Research Site

Taoyuan District, 333, Taiwan

Location

Research Site

Adana, 01330, Turkey (Türkiye)

Location

Research Site

Ankara, 06590, Turkey (Türkiye)

Location

Research Site

Antalya, 07059, Turkey (Türkiye)

Location

Research Site

Bursa, 16059, Turkey (Türkiye)

Location

Research Site

Edirne, 22030, Turkey (Türkiye)

Location

Research Site

Istanbul, 34732, Turkey (Türkiye)

Location

Research Site

Izmir, 35340, Turkey (Türkiye)

Location

Research Site

Malatya, 44280, Turkey (Türkiye)

Location

Research Site

London, SW36JJ, United Kingdom

Location

Research Site

Preston, PR29HT, United Kingdom

Location

MeSH Terms

Conditions

Urinary Bladder DiseasesUrologic DiseasesUrinary Bladder NeoplasmsCarcinoma, Transitional Cell

Interventions

vofatamabB701 protein, Human herpesvirus 6Docetaxel

Condition Hierarchy (Ancestors)

Female Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteNeoplasmsCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenes

Results Point of Contact

Title
Chief Medical Officer
Organization
Rainier Therapeutics

Study Officials

  • Rainier Therapeutics

    Rainier Therapeutics

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 16, 2015

First Posted

March 30, 2015

Study Start

June 1, 2015

Primary Completion

November 1, 2019

Study Completion

November 1, 2019

Last Updated

March 9, 2020

Results First Posted

February 17, 2020

Record last verified: 2020-02

Data Sharing

IPD Sharing
Will not share

Locations