- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03343301
A Study of Bemarituzumab (FPA144) Combined With Modified FOLFOX6 in Gastric/Gastroesophageal Cancer (FIGHT)
FIGHT: A Phase 3 Randomized, Double-Blind, Controlled Study Evaluating FPA144 and Modified FOLFOX6 in Patients With Previously Untreated Advanced Gastric and Gastroesophageal Cancer: Phase 2 Preceded by Dose Finding in Phase 1
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
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Arizona
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Tucson, Arizona, United States, 85724
- The University of Arizona Cancer Center
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California
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Greenbrae, California, United States, 94904
- Marin Cancer Care
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Whittier, California, United States, 90603
- Innovative Clinical Research Institute
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Illinois
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Chicago, Illinois, United States, 90603
- The University of Chicago Medical Center
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Michigan
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Detroit, Michigan, United States, 48201
- Karmanos Cancer Institute
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New York
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Rochester, New York, United States, 14642
- Wilmont Cancer Institute
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Tennessee
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Knoxville, Tennessee, United States, 37909
- Tennessee Cancer Specialists
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Disease that is unresectable, locally advanced, or metastatic (not amendable to curative therapy)
- Understand and sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form (ICF) prior to any study-specific evaluation
- Life expectancy of at least 3 months in the opinion of the investigator
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Age ≥ 18 years at the time the ICF is signed
In sexually active patients (women of childbearing potential and males), willingness to use 2 effective methods of contraception, of which 1 must be a physical barrier method (condom, diaphragm, or cervical/vault cap) until 6 months after the last dose of FPA144. Other effective forms of contraception include:
- Permanent sterilization (hysterectomy and/or bilateral oophorectomy, or bilateral tubal ligation with surgery, or vasectomy) at least 6 months prior to Screening
- Women of childbearing potential who are on stable oral contraceptive therapy or intrauterine or implant device for at least 90 days prior to the study, or abstain from sexual intercourse as a way of living
Adequate hematological and biological function, confirmed by the following laboratory values within 96 hours prior to enrollment:
Bone Marrow Function
- Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L
- Platelets ≥ 100 × 10^9/L
- Hemoglobin ≥ 9 g/dL
Hepatic Function
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 × upper limit of normal (ULN); if liver metastases, then < 5 × ULN
- Bilirubin < 1.5 × ULN except in patients with Gilbert's disease
Renal Function
- Calculated creatinine clearance using cockcroft Gault formula ≥ 50 mL/min or estimated glomerular filtrate rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula ≥ 50 mL/min
- International normalized ratio (INR) or prothrombin time (PT) < 1.5 x the ULN except for patients receiving anticoagulation, who must be on a stable dose of warfarin for 6 weeks prior to enrollment
- Measurable or non-measurable, but evaluable disease using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Histologically or cytologically confirmed GI malignancy for which mFOLFOX6 is considered an appropriate treatment (e.g., gastric cancer [GC], colorectal carcinoma, pancreatic adenocarcinoma)
- Patient must be a candidate to receive at least 2 doses of mFOLFOX6 chemotherapy
Exclusion Criteria:
- Untreated or symptomatic central nervous system (CNS) metastases (CNS imaging not required). Patients with asymptomatic CNS metastases are eligible provided they have been clinically stable for at least 4 weeks and do not require intervention such as surgery, radiation, or any corticosteroid therapy for management of symptoms related to CNS disease
Impaired cardiac function or clinically significant cardiac disease, including any of the following (Criteria a through g):
- Unstable angina pectoris ≤ 6 months prior to enrollment
- Acute myocardial infarction ≤ 6 months prior to enrollment
- New York Heart Association Class II-IV congestive heart failure
- Uncontrolled hypertension (as defined as ≥ 160/90 despite optimal medical management)
- Uncontrolled cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
- Active coronary artery disease
- Fridericia's corrected QT interval (QTcF) ≥ 480
- Peripheral sensory neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
- Active infection requiring systemic treatment or any uncontrolled infection ≤ 14 days prior to enrollment
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known active or chronic hepatitis B or C infection
- History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis)
- Evidence or history of bleeding diathesis or coagulopathy
- Radiotherapy ≤ 28 days of enrollment. Patients must be recovered from all acute radiotherapy-related toxicities. No radiopharmaceuticals (strontium, samarium) within 8 weeks of enrollment
- Prior treatment with any selective inhibitor (e.g., AZD4547, BGJ398, JNJ-42756493, BAY1179470) of the fibroblast growth factor (FGF)-FGFR pathway
- Ongoing adverse effects from prior systemic treatment > CTCAE Grade 1 (with the exception of Grade 2 alopecia)
- Participation in another therapeutic clinical study or receiving any investigational agent within 28 days of enrollment or during this clinical study
- Corneal defects, corneal ulcerations, keratitis, keratoconus, history of corneal transplant, or other known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer
- Known positivity for human epidermal growth factor receptor 2 (HER2) (as defined by a positive immunohistochemistry [IHC] test of 3+ or IHC of 2+ with fluorescent in situ hybridization [FISH])
- Major surgical procedures not permitted ≤ 28 days prior to enrollment. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before enrollment. In all cases the patient must be sufficiently recovered and stable before treatment administration
- Women who are pregnant or breastfeeding (unless the patient is willing to interrupt breastfeeding during study treatment administration and then resume 6 months after study discontinuation); women of childbearing potential must not consider getting pregnant during the study
- Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, psychiatric disturbance, uncontrolled intercurrent illness including arterial thrombosis, or symptomatic pulmonary embolism)
- Presence of any other condition that may increase the risk associated with study participation, or may interfere with the interpretation of study results, and, in the opinion of the investigator, would make the patient inappropriate for entry in the study
- Known allergy, hypersensitivity or contraindication to components of the FPA144 formulation including polysorbate or to platinum-containing medications, 5-FU, or leucovorin
History of prior malignancy, except (Criteria a through f):
- Curatively treated non-melanoma skin malignancy
- Cervical cancer in situ
- Curatively treated Stage I uterine cancer
- Curatively treated ductal or lobular breast carcinoma in situ and not currently receiving any systemic therapy
- Localized prostate cancer that has been treated surgically with curative intent and presumed cured
- Solid tumor treated curatively more than 5 years previously without evidence of recurrence
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Bemarituzumab 6 mg/kg + mFOLFOX6
Participants received 6 mg/kg bemarituzumab administered every 2 weeks (Q2W) and mFOLFOX6 chemotherapy administered Q2W until unacceptable toxicity, disease progression, or death.
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Administered by intravenous infusion over approximately 30 minutes
Other Names:
Modified FOLFOX6 regimen consists of the following:
Other Names:
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Experimental: Bemarituzumab 15 mg/kg + mFOLFOX6
Participants received 15 mg/kg bemarituzumab administered Q2W with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W.
Treatment continued until unacceptable toxicity, disease progression, or death.
|
Administered by intravenous infusion over approximately 30 minutes
Other Names:
Modified FOLFOX6 regimen consists of the following:
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment-related Adverse Events ≥ Grade 2
Time Frame: From first dose of study drug up to 28 days after last dose; Actual median (min, max) duration of treatment emergent period was 19.3 (12.3, 22.3) weeks in the bemarituzumab 6 mg/kg group and 19.4 (4.0, 35.4) weeks in the bemarituzumab 15 mg/kg group.
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A treatment-related adverse event (TRAE) is defined as an adverse event (AE) with an onset date on or after the date of first dose of study treatment, or an event present before treatment that worsened after treatment, and with an onset date prior to 28 days after the last date of dose, for which the investigator assessed as related to investigational product The investigator classified the severity of each AE using the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 on a scale from mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death due to the AE (Grade 5).
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From first dose of study drug up to 28 days after last dose; Actual median (min, max) duration of treatment emergent period was 19.3 (12.3, 22.3) weeks in the bemarituzumab 6 mg/kg group and 19.4 (4.0, 35.4) weeks in the bemarituzumab 15 mg/kg group.
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Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: 28 days
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DLTs were defined as any of the following events considered by the investigator to be related to study drug:
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28 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment-emergent Adverse Events
Time Frame: From first dose of study drug up to 28 days after last dose; Actual median (min, max) duration of the treatment emergent period was 19.3 (12.3, 22.3) weeks in the bemarituzumab 6 mg/kg group and 19.4 (4.0, 35.4) weeks in the bemarituzumab 15 mg/kg group.
|
Treatment-emergent adverse events are defined as adverse events (AEs) that started or worsened between the start of study drug and 28 days after permanent discontinuation of study drug. A serious AE is defined as any untoward medical occurrence that at any dose:
The investigator assessed the causality/relationship between the study treatment and each AE, and assessed the severity of each AE according to the guidelines provided in NCI-CTCAE, version 5.0 on a scale from mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death due to the AE (Grade 5). Ocular events associated with symptomatic corneal involvement and symptomatic and asymptomatic retinal involvement were events of special interest in this study. |
From first dose of study drug up to 28 days after last dose; Actual median (min, max) duration of the treatment emergent period was 19.3 (12.3, 22.3) weeks in the bemarituzumab 6 mg/kg group and 19.4 (4.0, 35.4) weeks in the bemarituzumab 15 mg/kg group.
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Maximum Observed Serum Concentration (Cmax) of Bemarituzumab
Time Frame: Cycle 1 day 1 at predose, 0.25, 4, 48, and 168 hours after end of infusion, and for participants in Cohort 2 day 8 at 0.25 and 4 hours end of infusion; Cycle 2 day 1 at predose, 0.25 and 48 hours after end of infusion.
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Cycle 1 day 1 at predose, 0.25, 4, 48, and 168 hours after end of infusion, and for participants in Cohort 2 day 8 at 0.25 and 4 hours end of infusion; Cycle 2 day 1 at predose, 0.25 and 48 hours after end of infusion.
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Observed Serum Concentration of Bemarituzumab at the End of the Dose Interval (Ctrough)
Time Frame: Cycle 1 day 14 predose for cohort 1 and day 8 predose for cohort 2; Cycle 2 day 14 predose
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Cycle 1 day 14 predose for cohort 1 and day 8 predose for cohort 2; Cycle 2 day 14 predose
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Area Under the Observed Concentration-time Curve From the Time of Dosing to Day 14 (AUC0-14)
Time Frame: Cycle 1 day 1 at predose, 0.25, 4, 48, and 168 hours after end of infusion, and for participants in Cohort 2 day 8 at 0.25 and 4 hours after the end of infusion.
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Area under the observed concentration-time curve from the time of dosing to Day 14 (0-336h) calculated by log-linear trapezoidal approximation.
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Cycle 1 day 1 at predose, 0.25, 4, 48, and 168 hours after end of infusion, and for participants in Cohort 2 day 8 at 0.25 and 4 hours after the end of infusion.
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Terminal Half-life (t1/2) of Bemarituzumab
Time Frame: Cycle 1 day 1 at predose, 0.25, 4, 48, and 168 hours after end of infusion, and for participants in Cohort 2 day 8 at 0.25 and 4 hours after end of infusion.
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Cycle 1 day 1 at predose, 0.25, 4, 48, and 168 hours after end of infusion, and for participants in Cohort 2 day 8 at 0.25 and 4 hours after end of infusion.
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Number of Participants With Treatment Induced Anti-bemarituzumab Antibodies
Time Frame: Samples were collected for ADA analysis predose on day 1 of Cycles 1, 2, 3, 7, and 10 and at 28 days following the last dose.
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Postbaseline treatment induced antidrug antibody (ADA) positive is defined as participants with
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Samples were collected for ADA analysis predose on day 1 of Cycles 1, 2, 3, 7, and 10 and at 28 days following the last dose.
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: MD, Amgen
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- FPA144-004 Phase 1
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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