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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 : Recruiting
First Posted : March 30, 2015
Last Update Posted : October 18, 2018
Sponsor:
Information provided by (Responsible Party):
Rainier Therapeutics

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).

Condition or disease Intervention/treatment Phase
Locally Advanced or Metastatic Urothelial Cell Carcinoma Urinary Bladder Disease Urological Diseases Drug: Vofatamab Drug: Docetaxel Drug: Placebo Phase 1 Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Study Start Date : June 2015
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Docetaxel

Arm Intervention/treatment
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.

Drug: Vofatamab
Other Names:
  • B-701
  • MFGR1877S
  • R3Mab

Drug: Docetaxel
Other Names:
  • Docefrez
  • Taxotere

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

Drug: Docetaxel
Other Names:
  • Docefrez
  • Taxotere

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.

Drug: Vofatamab
Other Names:
  • B-701
  • MFGR1877S
  • R3Mab




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02401542


Contacts
Contact: BioClin Therapeutics 925-413-6140 clin-ops@bioclintherapeutics.com
Contact: Werner Gladdines wgladdines@bioclintherapeutics.com

  Show 67 Study Locations
Sponsors and Collaborators
Rainier Therapeutics
Investigators
Study Chair: BioClin Therapeutics Sponsor GmbH

Responsible Party: Rainier Therapeutics
ClinicalTrials.gov Identifier: NCT02401542     History of Changes
Other Study ID Numbers: B-701-U21
2017-001319-36 ( EudraCT Number )
First Posted: March 30, 2015    Key Record Dates
Last Update Posted: October 18, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rainier Therapeutics:
targeted therapy
second line therapy
combination therapy
Urothelial Cell Carcinoma
UCC
bladder cancer
vofatamab
FGFR3
invasive bladder cancer
Transitional Cell Carcinoma
TCC
Phase 2
monoclonal antibody
docetaxel
Phase 1
monotherapy

Additional relevant MeSH terms:
Carcinoma
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action