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A Study of FPA144 Combined With Modified FOLFOX6 in Gastric/Gastroesophageal Cancer (FIGHT)

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ClinicalTrials.gov Identifier: NCT03343301
Recruitment Status : Active, not recruiting
First Posted : November 17, 2017
Last Update Posted : August 2, 2018
Sponsor:
Information provided by (Responsible Party):
Five Prime Therapeutics, Inc.

Brief Summary:
This is a multi-center study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of FPA144 in combination with 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) for patients with gastrointestinal malignancies (GI). The phase 1 open label safety run-in will identify a recommended dose of FPA144 to use in the phase 3 portion of the trial.

Condition or disease Intervention/treatment Phase
Gastrointestinal Cancer Gastrointestinal Cancer Metastatic Gastric Cancer Combination Product: FPA144 + mFOLFOX6 Phase 1

Detailed Description:
Phase 1 is an open-label dose-escalation of FPA144 in combination with mFOLFOX6. Eligible patients will have unresectable locally advanced or metastatic GI cancer of any type and be candidates to receive at least 2 doses of mFOLFOX6 chemotherapy. FGFR2 status is not a requirement for enrollment. FGFR2 status will be tested retrospectively by immunohistochemistry (IHC) if tissue is available and a sample will be obtained for circulating tumor deoxynucleic acid (ctDNA) blood assay. Phase 1 consists of at least 2 dosing cohorts of FPA144 in combination with mFOLFOX6 to determine the recommended dose of FPA144 in combination with mFOLFOX6 in the phase 3.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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 3 Preceded by Dose Finding in Phase 1A
Actual Study Start Date : November 30, 2017
Estimated Primary Completion Date : July 24, 2018
Estimated Study Completion Date : February 28, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Phase 1 Study of FPA144 + mFOLFOX6

Phase 1 dose escalation of FPA144 administered intravenously over approximately 30 minutes in cohorts of 3-6 patients to evaluate for the recommended dose (RD) of FPA144 for phase 3. mFOLFOX6 administered 30 minutes after the end of the FPA144 infusion as follows:

  1. Oxaliplatin 85 mg/m2 intravenously over 2 hours on day 1
  2. Leucovorin 400 mg/m2 intravenously over 2 hours. Can be administered concurrently with oxaliplatin using a Y-connector on day 1
  3. Immediately after completion of oxaliplatin and leucovorin, administer 5-fluorouracil (5-FU) 400 mg/m2 intravenously over 5 minutes
  4. Immediately after the 5-FU bolus, 5-FU 2400 mg/m2 as a continuous intravenous infusion over 46 hours.

Treatment is repeated every 2 weeks.

Combination Product: FPA144 + mFOLFOX6
Dose escalation of FPA144 to identify recommended dose in combination with mFOLFOX6




Primary Outcome Measures :
  1. Incidence of Grade 3 and Grade 4 adverse events and clinical laboratory abnormalities defined as dose limiting toxicities [ Time Frame: 24 weeks ]
    Safety

  2. Recommended dose (RD) of FPA144 combined with mFOLFOX6 [ Time Frame: 8 months ]
    Tolerability

  3. Incidence of corneal thinning and/or corneal ulcers (identified using slit lamp exam with fluorescein stain) and any retinal changes (identified using ocular coherence tomogram) [ Time Frame: 8 months ]
    Safety


Secondary Outcome Measures :
  1. Area under serum concentration-time curve of FPA144 in day*µg/mL [ Time Frame: 10 months ]
    Pharmacokinetic profile FPA144

  2. Maximum serum concentration of FPA144 in µg/mL [ Time Frame: 10 months ]
    Pharmacokinetic Profile FPA144

  3. Trough serum concentration of FPA144 in µg/mL [ Time Frame: 12 months ]
    Pharmacokinetic Profile FPA144

  4. Clearance of FPA144 in mL/day/kg [ Time Frame: 10 months ]
    Pharmacokinetic Profile FPA144

  5. Terminal Half-Life of FPA144 in day [ Time Frame: 10 months ]
    Pharmacokinetic Profile FPA144

  6. Volume of distribution (mL/kg) and accumulation ratio of FPA144 [ Time Frame: 10 months ]
    Pharmacokinetic Profile FPA144

  7. Incidence of treatment emergent anti-FPA144 antibody response (levels in serum) [ Time Frame: 10 months ]
    Immunogenicity FPA144

  8. Pharmacodynamic profile of FPA144 [ Time Frame: 12 months ]
    Biomarker analysis of the fibroblast growth factor receptor (FGFR) pathway in blood



Information from the National Library of Medicine

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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

Inclusion Criteria:

  1. Disease that is unresectable, locally advanced, or metastatic (not amendable to curative therapy)
  2. Understand and sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form (ICF) prior to any study-specific evaluation
  3. Life expectancy of at least 3 months in the opinion of the investigator
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  5. Age >/=18 years at the time the ICF is signed
  6. 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
  7. 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 × 109/L
    • Platelets >/= 100 × 109/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 cockroft Gault formula >/= 50 mL/min (see Appendix 1)
  8. 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
  9. Measurable or non-measurable, but evaluable disease using RECIST v1.1
  10. Histologically or cytologically confirmed GI malignancy for which mFOLFOX6 is considered an appropriate treatment (e.g., gastric cancer [GC], colorectal carcinoma, pancreatic adenocarcinoma)
  11. Patient must be a candidate to receive at least 2 doses of mFOLFOX6 chemotherapy

Exclusion Criteria:

  1. 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
  2. Impaired cardiac function or clinically significant cardiac disease, including any of the following (Criteria a through g):

    1. Unstable angina pectoris </=6 months prior to enrollment
    2. Acute myocardial infarction </=6 months prior to enrollment
    3. New York Heart Association Class II-IV congestive heart failure
    4. Uncontrolled hypertension (as defined as ≥ 160/90 despite optimal medical management)
    5. Uncontrolled cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
    6. Active coronary artery disease
    7. Fridericiaís corrected QT interval (QTcF) >/= 480
  3. Peripheral sensory neuropathy >/= Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
  4. Active infection requiring systemic treatment or any uncontrolled infection </= 14 days prior to enrollment
  5. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known active or chronic hepatitis B or C infection
  6. History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis)
  7. Evidence or history of bleeding diathesis or coagulopathy
  8. Radiotherapy </= 28 days of enrollment. Patients must be recovered from all acute radiotherapy-related toxicities. No radiopharmaceuticals (strontium, samarium) within 8 weeks of enrollment
  9. Prior treatment with any selective inhibitor (e.g., AZD4547, BGJ398, JNJ-42756493, BAY1179470) of the fibroblast growth factor (FGF)-FGFR pathway
  10. Ongoing adverse effects from prior systemic treatment > NCI CTCAE Grade 1 (with the exception of Grade 2 alopecia)
  11. Participation in another therapeutic clinical study or receiving any investigational agent within 28 days of enrollment or during this clinical study
  12. 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
  13. Known positivity for HER2 (as defined by a positive IHC test of 3+ or IHC of 2_ with fluorescent in situ hybridization [FISH])
  14. 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
  15. 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
  16. 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)
  17. 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
  18. Known allergy, hypersensitivity or contraindication to components of the FPA144 formulation including polysorbate or to platinum-containing medications, 5-FU, or leucovorin
  19. History of prior malignancy, except (Criteria a through f):

    1. Curatively treated non-melanoma skin malignancy
    2. Cervical cancer in situ
    3. Curatively treated Stage I uterine cancer
    4. Curatively treated ductal or lobular breast carcinoma in situ and not currently receiving any systemic therapy
    5. Localized prostate cancer that has been treated surgically with curative intent and presumed cured
    6. Solid tumor treated curatively more than 5 years previously without evidence of recurrence

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): NCT03343301


Locations
United States, California
Marin Cancer Care
Greenbrae, California, United States, 94904
Innovative Clinical Research Institute
Whittier, California, United States, 90603
Sponsors and Collaborators
Five Prime Therapeutics, Inc.
Investigators
Study Director: Medical Lead Five Prime Therapeutics, Inc.

Responsible Party: Five Prime Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03343301     History of Changes
Other Study ID Numbers: FPA144-004
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: August 2, 2018
Last Verified: July 2018

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

Keywords provided by Five Prime Therapeutics, Inc.:
gastrointestinal cancer

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases