Dose Escalation, Expansion Study of Vofatamab (B-701) in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma (FIERCE-21)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT02401542 |
|
Recruitment Status :
Terminated
(program has been put on hold by the sponsor)
First Posted : March 30, 2015
Results First Posted : February 17, 2020
Last Update Posted : March 9, 2020
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
| 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 |
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) |
| Actual Enrollment : | 71 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| 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 |
| Actual Primary Completion Date : | November 1, 2019 |
| Actual Study Completion Date : | November 1, 2019 |
| 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:
Drug: Docetaxel Other Names:
|
|
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:
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:
|
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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
Show 65 study locations
| Study Chair: | Rainier Therapeutics | Rainier Therapeutics |
Documents provided by Rainier Therapeutics:
| Responsible Party: | Rainier Therapeutics |
| ClinicalTrials.gov Identifier: | NCT02401542 |
| Other Study ID Numbers: |
B-701-U21 2017-001319-36 ( EudraCT Number ) |
| First Posted: | March 30, 2015 Key Record Dates |
| Results First Posted: | February 17, 2020 |
| Last Update Posted: | March 9, 2020 |
| Last Verified: | February 2020 |
| 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 |
|
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 |
|
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 |