A Phase 1b/2 Study of B-701 in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma (FIERCE 21)

Study Description

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Brief Summary:

This is a Phase 1b/2, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of B-701 plus docetaxel versus placebo plus docetaxel in the treatment of locally advanced or metastatic urothelial cell carcinoma in subjects who have relapsed after, or are refractory to standard therapy.

Condition or disease	Intervention/treatment	Phase
Locally Advanced or Metastatic Urothelial Cell Carcinoma; Urinary Bladder Disease; Urological Diseases	Drug: B-701; Drug: Docetaxel; Drug: placebo	Phase 1; Phase 2

Detailed Description:

This is a Phase 1b/2, randomized, double-blind, placebo-controlled, multicenter, parallel-group, efficacy and safety study of B-701 plus docetaxel versus placebo plus docetaxel in the treatment of 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 2 phases: Lead-In Phase and Randomized Phase; and the Lead-In Phase is divided into 3 cohorts. In Cohorts 1 and 2, all subjects will receive both B-701 plus docetaxel (unblinded). In Cohort 3, all subjects will receive B-701 only (unblinded). Subjects enrolling in Cohorts 2 and 3, as well as the Randomized Phase of the study, must have tumors with FGFR3 mutations or gene fusions.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	261 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	A Phase 1b/2, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Study of B-701 Plus Docetaxel Versus Placebo Plus Docetaxel in the Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma in Subjects Who Have Relapsed After, or Are Refractory to Standard Therapy
Study Start Date :	June 2015
Estimated Primary Completion Date :	December 2018
Estimated Study Completion Date :	December 2018

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: B-701 plus docetaxel; IV infusion B-701, 25 mg/kg plus docetaxel, 75 mg/m2 on day one of each 21-day cycle	Drug: B-701 Drug: Docetaxel
Placebo Comparator: Placebo plus docetaxel; IV infusion placebo plus docetaxel, 75 mg/m2 on day one of each 21-day cycle	Drug: Docetaxel Drug: placebo
Experimental: B-701; IV infusion B-701, 25 mg/kg	Drug: B-701

Outcome Measures

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Primary Outcome Measures :

1. 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 ]

Secondary Outcome Measures :

1. 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 ]
2. 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 ]
3. 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 ]
4. Evaluate the efficacy of B-701 plus docetaxel compared with placebo plus docetaxel as measured by overall survival (OS) [ Time Frame: 3-4 years ]
5. 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 ]
6. Safety and tolerability assessed through summaries of AEs [ Time Frame: 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
7. Safety and tolerability assessed through summaries of physical examination findings [ Time Frame: 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.
8. Safety and tolerability assessed through summaries of laboratory laboratory results [ Time Frame: 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.
9. Safety and tolerability assessed through summaries of ECG results. [ Time Frame: 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.
10. Evaluate FGFR3 Expression [ Time Frame: 3-4 years ]
    To study the association between the level of FGFR3 expression in primary tumors or metastases with efficacy and/or adverse event (AE) outcomes.
11. Evaluation of FGFR3 mutations or fusions in primary tumors or metastases [ Time Frame: 3-4 years ]
    To study the association between the presence of FGFR3 mutations or fusions in primary tumors or metastases with efficacy and/or adverse event (AE) outcomes.

Eligibility Criteria

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

Criteria

Key Inclusion Criteria:

• Available tissue that was obtained at or after the time the usbject was found to have muscle invasive disease and is of suitable quality and quantity and to assess the FGFR3 status by genetic testing. For subjects participating in the Randomized Phase only, if suitable archival tissue is unavailable, then a core biopsy of tumor tissue (metastatic or primary) must be obtained prior to randomization even if a blood sample sample was used to determine FGFR3 genetic status
• Stage IV, locally advanced or metastatic urothelial bladder cancer or transitional cell carcinoma arising in another location of the urinary tract, including urethra, ureter, and renal pelvis
• Relapsed after or are refractory to at least one prior line of chemotherapy which have not included a taxane (with the exception of Cohort 3 of the Lead-In Phase which will allow the enrollment of subjects with prior treatment with a taxane)
• At least one prior chemotherapeutic regimen for advanced metastatic/recurrent disease, of which at least one regimen included a platinum agent (unless contraindicated)
• Measurable disease according to RECIST v1.1 criteria
• For Cohort 2, Cohort 3, and the Randomized Phase, tumor must be shown to have an FGFR3 mutation or gene fusion.

Main Exclusion Criteria:

• Prior anti-cancer therapy within 4 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
• Weight > 110kg

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Izzy Cornelio	(323) 401-3093	icornelio@bioclintherapeutics.com
Contact: Werner Gladdines		wgladdines@bioclintherapeutics.com

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Sponsors and Collaborators

BioClin Therapeutics, Inc.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	BioClin Therapeutics, Inc.
ClinicalTrials.gov Identifier:	NCT02401542 History of Changes
Other Study ID Numbers:	B-701-U21; 2017-001319-36 ( EudraCT Number )
First Posted:	March 30, 2015
Last Update Posted:	December 5, 2017
Last Verified:	December 2017
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 BioClin Therapeutics, Inc.:

targeted therapy; second line therapy; combination therapy; Urothelial Cell Carcinoma; UCC; bladder cancer; B-701; FGFR3	invasive bladder cancer; Transitional Cell Carcinoma; TCC; Phase 2; monoclonal antibody; docetaxel; Phase 1

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