Locally Advanced or Metastatic Urothelial Cell CarcinomaPhase 1/2FIERCE-21NCT02401542
Dose Escalation, Expansion Study of Vofatamab (B-701) in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma
A Phase 1/2 study testing Vofatamab and Docetaxel in people with Locally Advanced or Metastatic Urothelial Cell Carcinoma and Urinary Bladder Disease, run by Rainier Therapeutics at 65 sites in 9 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced or Metastatic Urothelial Cell Carcinoma, Urinary Bladder Disease, Urological Diseases
- What is being tested?
- Vofatamab and Docetaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 71 participants
- Where
- 65 sitesin 9 countries
- Study dates
- Jun 2015to 1 Nov 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Key Disease Specific Inclusion Criteria:
- 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)
Phase 2 and Phase 2b Specific Inclusion Criteria:
- Patient must be confirmed to have a FGFR3 genomic alteration at the time of documentation of advanced disease.
- 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
Trial locations and contacts
65 sites in 9 countries.
65 sites in 9 countries
Spain16 sites
Research Site
Badalona, 08916
Research Site
Barcelona, 08003
Research Site
Barcelona, 08026
Research Site
Barcelona, 08036
Research Site
Barcelona, 08908
Research Site
Granada, 18014
Research Site
Lugo, 27003
Research Site
Madrid, 28007
Research Site
Madrid, 28033
Research Site
Madrid, 28041
Research Site
Madrid, 28046
Research Site
Madrid, 28050
Research Site
Oviedo, 33011
Research Site
Pamplona, 31008
Research Site
Valencia, 46009
Research Site
Vigo, 36204
United States11 sites
Research Site
Boston, Massachusetts, 02215
Research Site
Dallas, Texas, 75390-9110
Research Site
Detroit, Michigan, 48201
Research Site
Duarte, California, 91010
Reaserach Site
Fort Wayne, Indiana, 46845
Research Site
Gilbert, Arizona, 85234
Research Site
Goodyear, Arizona, 85338
Research Site
Louisville, Kentucky, 40202
Research Site
Miami, Florida, 33140
Research Site
Rochester, Minnesota, 55905
Research Site
Syracuse, New York, 13210
Italy9 sites
Research Site
Ancona, 60126
Research Site
Catania, 95123
Research Site
Milan, 20132
Research Site
Milan, 20133
Research Site
Milan, 20141
Research Site
Modena, 41124
Research Site
Naples, 80131
Research Site
Negrar, 37024
Research Site
Siena, 53100
South Korea8 sites
Research Site
Gwangju, 61469
Research Site
Incheon, 405-760
Research Site
Seongnam-si, 13620
Research Site
Seoul, 02841
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Taiwan8 sites
Research Site
Kaohsiung City, 81362
Research Site
Kaohsiung City, 83301
Research Site
Taichung, 40447
Research Site
Taichung, 435
Research Site
Tainan, 704
Research Site
Taipei, 110
Research Site
Taipei, 11217
Research Site
Taoyuan, 333
Turkey (Türkiye)8 sites
Research Site
Adana, 01330
Research Site
Ankara, 06590
Research Site
Antalya, 07059
Research Site
Bursa, 16059
Research Site
Edirne, 22030
Research Site
Istanbul, 34732
Research Site
Izmir, 35340
Research Site
Malatya, 44280
United Kingdom2 sites
Research Site
London, SW36JJ
Research Site
Preston, PR29HT
About this study
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
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).
Read the 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).
- Conditions
- Locally Advanced or Metastatic Urothelial Cell Carcinoma, Urinary Bladder Disease, Urological Diseases
- Being tested
- Vofatamab, Docetaxel, Placebo
- Keywords
- Urothelial Cell Carcinoma, UCC, bladder cancer, vofatamab, FGFR3, invasive bladder cancer, targeted therapy, Transitional Cell Carcinoma, TCC, Phase 2, second line therapy, monoclonal antibody, docetaxel, combination therapy, Phase 1, monotherapy, B-701
- Medical subject headings
- Urinary Bladder Diseases, Urologic Diseases, Urinary Bladder Neoplasms, Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VofatamabDrug
Also called B-701, MFGR1877S, R3Mab
DocetaxelDrug
Also called Docefrez, Taxotere
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Vofatamab; Drug: 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 Receives: Drug: Docetaxel; Drug: 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. Receives: Drug: Vofatamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3-4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2015 (estimated)
- Study startJun 2015
- Primary completion1 Nov 2019
- Study completion1 Nov 2019
Why it stopped: program has been put on hold by the sponsor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Locally Advanced or Metastatic Urothelial Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rainier Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rainier Therapeutics, Study chair, Rainier Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02401542
- Sponsor's protocol ID
- B-701-U21
- Other IDs
- 2017-001319-36, 2017
- Acronym
- FIERCE-21
- Status last verified
- Feb 2020
- First submitted
- 16 Mar 2015
- Last updated
- 9 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02401542
- Acronym / sponsor ID
- FIERCE-21 / B-701-U21
- Conditions
- Locally Advanced or Metastatic Urothelial Cell Carcinoma, Urinary Bladder Disease, Urological Diseases
- Keywords
- Urothelial Cell Carcinoma, UCC, bladder cancer, vofatamab, FGFR3, invasive bladder cancer, targeted therapy, Transitional Cell Carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: program has been put on hold by the sponsor
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Rainier TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jun 2015
- Primary completion
- 1 Nov 2019 (actual)
- Study completion
- 1 Nov 2019 (actual)
- First posted
- 30 Mar 2015 (estimated)
- Results
- Posted 17 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Vofatamab plus docetaxel | Active comparator | Drug: Vofatamab, Drug: DocetaxelIV 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. |
| Placebo plus docetaxel | Placebo comparator | Drug: Docetaxel, Drug: PlaceboIV 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 |
| Vofatamab | Experimental | Drug: VofatamabIV 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VofatamabAlso: B-701, MFGR1877S, R3Mab | Drug | Vofatamab, Vofatamab plus docetaxel |
| DocetaxelAlso: Docefrez, Taxotere | Drug | Placebo plus docetaxel, Vofatamab plus docetaxel |
| Placebo | Drug | Placebo plus docetaxel |
Primary outcome
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. 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rainier Therapeutics study chair
Rainier Therapeutics
65 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Vofatamab and Docetaxel in people with Locally Advanced or Metastatic Urothelial Cell Carcinoma and Urinary Bladder Disease, run by Rainier Therapeutics at 65 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 65 sites in Spain, United States, Italy, South Korea, Taiwan and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Efficacy Outcome: Progression Free Survival (PFS) (time frame: 3-4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2020.