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Trial record 1 of 1 for:    NCT02401542
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Dose Escalation, Expansion Study of Vofatamab (B-701) in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma (FIERCE-21)

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ClinicalTrials.gov Identifier: NCT02401542
Recruitment Status : Active, not recruiting
First Posted : March 30, 2015
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
Rainier Therapeutics

Tracking Information
First Submitted Date  ICMJE March 16, 2015
First Posted Date  ICMJE March 30, 2015
Last Update Posted Date April 10, 2019
Study Start Date  ICMJE June 2015
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 25, 2018)
Primary Efficacy Outcome: Progression Free Survival (PFS) [ Time Frame: 3-4 years ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 27, 2015)
  • Evaluate the efficacy of B-701 plus docetaxel compared with placebo plus docetaxel as measured by progression-free survival (PFS) [ Time Frame: up to 3-4 years ]
  • Evaluate the safety and tolerability of B-701 plus docetaxel compared with placebo plus docetaxel in the treatment of subjects with UCC as measured by AEs [ Time Frame: up to 3-4 years ]
  • Evaluate the safety and tolerability of B-701 plus docetaxel compared with placebo plus docetaxel in the treatment of subjects with UCC as measured by physical examinations. [ Time Frame: up to 3-4 years ]
  • Evaluate the safety and tolerability of B-701 plus docetaxel compared with placebo plus docetaxel in the treatment of subjects with UCC as measured by laboratory results. [ Time Frame: up to 3-4 years ]
  • Evaluate the safety and tolerability of B-701 plus docetaxel compared with placebo plus docetaxel in the treatment of subjects with UCC as measured by electrocardiogram (ECG) results. [ Time Frame: up to 3-4 years ]
Change History Complete list of historical versions of study NCT02401542 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2018)
  • Secondary Efficacy Outcome: Overall Survival (OS) [ Time Frame: up to 3-4 years ]
    Efficacy of vofatamab plus docetaxel, compared with docetaxel plus placebo, and vofatamab alone as measured by OS; measured from randomization to death. A patient has had to receive at least one vofatamab dose.
  • Efficacy Outcome - Objective Response Rate (ORR) [ Time Frame: up to 3-4 years ]
    Efficacy of vofatamab plus docetaxel, compared with docetaxel plus placebo, and vofatamab alone as measured by ORR; defined as the percentage of subjects who have baseline measurable disease and who achieve a best response of either complete response (CR) or partial response (PR) as assessed by the investigator using RECIST 1.1 criteria.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2015)
  • Evaluate the efficacy of B-701 plus docetaxel compared with placebo plus docetaxel as measured by objective response rates (ORR) [ Time Frame: up to 3-4 years ]
  • Evaluate the efficacy of B-701 plus docetaxel compared with placebo plus docetaxel as measured by disease control rate (DCR) [ Time Frame: up to 3-4 years ]
  • Evaluate the efficacy of B-701 plus docetaxel compared with placebo plus docetaxel as measured by duration of objective response (DOR) [ Time Frame: 3-4 years ]
  • Evaluate the efficacy of B-701 plus docetaxel compared with placebo plus docetaxel as measured by overall survival (OS) [ Time Frame: 3-4 years ]
  • Evaluate the efficacy of B-701 plus docetaxel compared with placebo plus docetaxel as measured by quality of life (QOL) [ Time Frame: 3-4 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Escalation, Expansion Study of Vofatamab (B-701) in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma
Official Title  ICMJE 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
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).
Detailed 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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Locally Advanced or Metastatic Urothelial Cell Carcinoma
  • Urinary Bladder Disease
  • Urological Diseases
Intervention  ICMJE
  • Drug: Vofatamab
    Other Names:
    • B-701
    • MFGR1877S
    • R3Mab
  • Drug: Docetaxel
    Other Names:
    • Docefrez
    • Taxotere
  • Drug: Placebo
Study Arms  ICMJE
  • Active Comparator: 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.

    Interventions:
    • Drug: Vofatamab
    • Drug: Docetaxel
  • Placebo Comparator: 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

    Interventions:
    • Drug: Docetaxel
    • Drug: Placebo
  • Experimental: 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.

    Intervention: Drug: Vofatamab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 25, 2018)
300
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2015)
211
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czechia,   Italy,   Korea, Republic of,   Spain,   Sweden,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02401542
Other Study ID Numbers  ICMJE B-701-U21
2017-001319-36 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Rainier Therapeutics
Study Sponsor  ICMJE Rainier Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Rainier Therapeutics Rainier Therapeutics
PRS Account Rainier Therapeutics
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP