ARQ 087 in Subjects With FGFR2 Gene Fusion Positive Inoperable or Adva

ARQ 087 in Subjects With FGFR2 Gene Fusion Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma

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https://clinicaltrials.gov/ct2/show/NCT03230318

Purpose
This pivotal, open-label, single-arm study will evaluate the anti-cancer activity of ARQ 087 by Objective Response Rate (ORR) by central radiology review as per RECIST v1.1 in subjects with inoperable or advanced intrahepatic cholangiocarcinoma (iCCA) whose tumors harbor FGFR2 gene fusions (by FISH performed by the central laboratory) and who received at least one prior regimen of systemic therapy. Subjects will be dosed orally once per day at 300 mg of ARQ 087 capsules.

Condition Intervention Phase
Intrahepatic Cholangiocarcinoma
Combined Hepatocellular and Cholangiocarcinoma
Drug: ARQ 087
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Pivotal Trial of ARQ 087 in Subjects With FGFR2 Gene Fusion Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma

Resource links provided by NLM:

Genetics Home Reference related topics: Crouzon syndrome Pfeiffer syndrome cholangiocarcinoma
MedlinePlus related topics: Genes and Gene Therapy
Genetic and Rare Diseases Information Center resources: Biliary Tract Cancer Bile Duct Cancer Intrahepatic Cholangiocarcinoma Crouzon Syndrome Pfeiffer Syndrome
U.S. FDA Resources

Further study details as provided by ArQule:

Primary Outcome Measures:
Anti-cancer activity of ARQ 087 by Objective Response Rate (ORR) [ Time Frame: Up to approximately 32 weeks ]
ORR will be assessed by central radiology review per RECIST version 1.1

Secondary Outcome Measures:
Safety of ARQ 087 as assessed by adverse events [ Time Frame: Up to approximately 36 weeks ]
Adverse events will be graded using NCI CTCAE guidelines, version 4.03

Anti-cancer activity of ARQ 087 by progression free survival (PFS) [ Time Frame: Up to approximately 32 weeks ]
PFS will be assessed by central radiology review per RECIST version 1.1

Anti-cancer activity of ARQ 087 by overall survival (OS) [ Time Frame: Up to approximately 36 weeks ]
OS will be calculated from the first date of receiving study drug until death

Anti-cancer activity of ARQ 087 by duration of response (DoR) [ Time Frame: Up to approximately 32 weeks ]
DoR will be assessed by central radiology review per RECIST version 1.1

Estimated Enrollment: 100
Anticipated Study Start Date: August 2017
Estimated Study Completion Date: March 2021
Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARQ 087 Drug: ARQ 087
ARQ 087 will be orally administered at 300 mg once per day with or without food and is supplied as 100 mg capsules.

Eligibility

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

Signed written informed consent granted prior to initiation of any study-specific procedures
18 years of age or older
Histologically or cytologically confirmed locally advanced, inoperable (where surgery is not indicated due to disease extension, co-morbidities, or other technical reasons), or metastatic iCCA or mixed histology tumors (combined hepatocellular-cholangiocarcinoma [cHCC-CCA])
FGFR2 gene fusion status confirmed by NGS or FISH testing

Test positive by FISH by the central laboratory designated by the Sponsor
Have FGFR2 gene fusion documented by a local or central laboratory using standard protocols and approved by local IRB/EC, by CLIA or other similar agency. If the FGFR2 gene fusion is identified by a laboratory other than the Sponsor’s central laboratory, then archival and/or recent tissue biopsy samples or a tissue block suitable for genetic testing must be available for confirmatory testing by FISH by the Sponsor’s central laboratory. If a subject has documentation from a local or central laboratory indicating that they test negative for FGFR2 gene fusion, that subject may not be enrolled in the study.
Received at least one regimen of prior systemic therapy and then experienced documented radiographic progression or was not able to tolerate prior systemic therapy.

If the subject received at least 4 cycles of systemic therapy and no measurable tumor reduction compared to the previous scan is observed, such subject can be enrolled
If the subject received immunotherapy, the documented radiographic disease progression is required
If the subject experienced disease progression within 6 months of adjuvant therapy, such therapy should be considered as the line of treatment rather than adjuvant therapy
Measurable disease by RECIST version 1.1
ECOG performance status ≤ 1
Adequate organ functions as indicated by the following laboratory values (based on screening visit values from the central laboratory).

Hematological

Hemoglobin (Hgb) ≥ 9.0 g/dL
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
Platelet count ≥ 75 x 109/L
International normalized ratio (INR) 0.8 to upper limit of normal (ULN) or ≤ 3 for subjects receiving anticoagulant therapy such as Coumadin or heparin
Hepatic

Total bilirubin ≤ 2 x ULN
AST and ALT ≤ 3 ULN (≤ 5 x ULN for subjects with liver metastases)
Albumin ≥ 2.8 g/dL
Renal

Serum creatinine ≤ 1.5 x ULN
Creatinine clearance of ≥ 60 mL/min as estimated by the Cockcroft-Gault equation
Male or female subjects of child-producing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after the last dose of ARQ 087
Exclusion Criteria:

Systemic anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal, targeted therapy, or investigational agents within four weeks of the first dose of ARQ 087
Major surgery, locoregional therapy, or radiation therapy within four weeks of the first dose of ARQ 087
Previous treatment with any FGFR inhibitor (e.g., ponatinib, dovitinib, nintedanib, AZD4547, NVP-BGJ398, LY2784455, BAY1163877)

– Subjects who received less than four weeks of therapy and were unable to continue therapy due to toxicity will be allowed to participate

Unable or unwilling to swallow the complete daily dose of ARQ 087 capsules
Clinically unstable central nervous system (CNS) metastases (to be eligible, subjects must have stable disease ≥ 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and/or have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications)
Current evidence of corneal or retinal disorder, including but not limited to bullous/band keratopathy, keratoconjunctivitis, corneal abrasion, inflammation/ulceration, confirmed by ophthalmologic examination
Concurrent uncontrolled or active hepatobiliary disorders, untreated or ongoing complications after laparoscopic procedures or stent placement, including but not limited to active cholangitis, biloma or abscess (to be eligible, the subjects have to be treated and disorders/complications should be resolved within 2 weeks prior to the first dose of ARQ 087)
History of significant cardiac disorders:

Myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association (NYHA) classification within 6 months of the first dose of ARQ 087 (MI that occurred > 6 months prior to the first dose of ARQ 087 will be permitted)
QTcF >500 msec (males or females)
Significant gastrointestinal disorder(s) that could, in the opinion of the Investigator, interfere with the absorption, metabolism, or excretion of ARQ 087 (e.g., Crohn’s disease, ulcerative colitis, extensive gastric resection)
Previous malignancy within 2 years of the first dose of ARQ 087, except curatively treated or low grade malignancies such as non-melanoma skin cancer, carcinoma in-situ of the breast, cervix, and superficial bladder tumors
Concurrent uncontrolled illness not related to cancer, including but not limited to:

Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements
Known uncontrolled human immunodeficiency virus (HIV) infection
Blood or albumin transfusion within 5 days of the blood draw being used to confirm eligibility
Pregnant or breast feeding
Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03230318

Contacts
Contact: ArQule, Inc. 781-994-0300 ClinicalTrials@arqule.com

Locations
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact 781-994-0300 ClinicalTrials@arqule.com
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact 781-994-0300 ClinicalTrials@arqule.com
United States, Tennessee
Vanderbilt-Ingram Cancer Center Not yet recruiting
Nashville, Tennessee, United States, 37232
Contact 781-994-0300 ClinicalTrials@arqule.com
United States, Texas
University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact 781-994-0300 ClinicalTrials@arqule.com
United States, Washington
University of Washington Medical Center Not yet recruiting
Seattle, Washington, United States, 98109
Contact 781-994-0300 ClinicalTrials@arqule.com
Sponsors and Collaborators
ArQule
More Information

Responsible Party: ArQule
ClinicalTrials.gov Identifier: NCT03230318 History of Changes
Other Study ID Numbers: ARQ 087-301
Study First Received: July 24, 2017
Last Updated: July 24, 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 ArQule:
iCCA
intrahepatic cholangiocarcinoma
FGFR2 gene fusion
ARQ 087
biliary cancer
bile duct cancer
FGFR2 gene rearrangement
liver cancer
targeted therapy
combined hepatocellular and cholangiocarcinoma
cHCC-CCA

Additional relevant MeSH terms:
Cholangiocarcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on July 27, 2017