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Phase 1/2 Study of Derazantinib (ARQ 087) in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations

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: NCT01752920
Recruitment Status : Completed
First Posted : December 19, 2012
Results First Posted : October 28, 2021
Last Update Posted : March 9, 2022
Sponsor:
Collaborator:
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Information provided by (Responsible Party):
Basilea Pharmaceutica

Brief Summary:
This was an open-label, Phase 1/2, dose escalation and signal finding study of derazantinib administered to patients with advanced solid tumors (Part 1; Dose Escalation/Food-effect Cohorts) or with advanced solid tumors with FGFR genetic aberrations, including iCCA with FGFR2 gene fusion (Part 2; Expanded Cohort, signal finding).

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: Derazantinib low dose range Drug: Derazantinib middle dose range Drug: Derazantinib high dose range Drug: Derazantinib at recommended phase 2 dose (RP2D) Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 119 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of ARQ 087 in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations, Including Intrahepatic Cholangiocarcinoma With FGFR2 Gene Fusion
Actual Study Start Date : December 10, 2012
Actual Primary Completion Date : August 28, 2018
Actual Study Completion Date : August 28, 2018


Arm Intervention/treatment
Experimental: Low Dose Group
Patients who received derazantinib orally at dose levels from 25 mg every other day (QOD) - 200 mg daily (QD) on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.
Drug: Derazantinib low dose range
Derazantinib was administered orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule.

Experimental: Middle Dose Group
Patients who received derazantinib orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.
Drug: Derazantinib middle dose range
Derazantinib was administered orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule.

Experimental: High Dose Group
Patients who received derazantinib orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.
Drug: Derazantinib high dose range
Derazantinib was administered orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule.

Experimental: Expanded Cohort Group
Patients who received derazantinib orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.
Drug: Derazantinib at recommended phase 2 dose (RP2D)
Derazantinib was administered orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule.




Primary Outcome Measures :
  1. Number of Patients With Drug-related Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Adverse events were collected and reported from the time of receiving first dose of derazantinib to the end of study assessment and follow-up period (30-day post-treatment) ]
    Adverse events were graded for severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. CTCAE is classifying AEs and their associated severity from Grade 1 (Mild AE), Grade 2 (Moderate AE), Grade 3 (Severe or medically significant but not immediately life-threatening), Grade 4 (Life-threatening consequences) to Grade 5 (Death related to AE)


Secondary Outcome Measures :
  1. Proportion of Patients With an Objective Tumor Response Per RECIST 1.1 [ Time Frame: Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated. ]

    The number of patients with an objective tumor response, which included those with either a complete response (CR) or a partial response (PR) based on RECIST v1.1 guidelines which defines criteria for the radiological assessment in tumor response.

    The objective response rate (ORR) was defined as the proportion of patients with a CR or PR.


  2. Proportion of Patients With Disease Control Per RECIST 1.1 [ Time Frame: Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated. ]
    The number of patients with tumor disease control, which included those with either a complete or partial tumor response, or a stable disease (SD) based on RECIST v1.1 guidelines which defines criteria for the radiological assessment in tumor response. The disease control rate (DCR) was defined as the proportion of patients with CR, PR or SD.

  3. Progression-free Survival (PFS) [ Time Frame: Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated. ]
    PFS was calculated as the time from the date of first dose until documented radiographic disease progression or death from any cause, whichever occurred first. Disease progression is measured according to a specified radiologic increase in tumor size.



Information from the National Library of Medicine

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.


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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. Signed written informed consent granted
  2. Men or women ≥18 years of age
  3. Histologically or cytologically confirmed, locally advanced, inoperable, or metastatic solid tumors. Patients eligible for enrollment in the Expanded Cohort must have documented and/or confirmed FGFR genetic aberrations, including iCCA with FGFR2 gene fusion.
  4. Failure to respond to standard therapy, or for whom standard therapy does not exist.
  5. Evaluable or measurable disease
  6. Archival and/or fresh biopsy tissue samples must be available prior to the first dose of the study drug
  7. Life expectancy ≥ 12 weeks
  8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  9. Hemoglobin (Hgb) ≥ 9.0 g/dL
  10. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
  11. Platelet count ≥ 100 x 10^9/L
  12. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (≤ 2 x ULN for patients with cholangiocarcinoma)
  13. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 × ULN (≤ 5 x ULN for patients with liver metastases)
  14. Serum creatinine ≤ 1.5 x ULN or creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  15. Albumin ≥ 2.8 g/dL
  16. INR 0.8 to ULN or ≤ 3 for patients receiving anticoagulant therapy
  17. Men or women of child-producing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoid intercourse during the study and for 90 days after the last dose of study drug
  18. Women of childbearing potential must have a negative serum pregnancy test during Screening Period and within 48 hours of the first dose of derazantinib.

Exclusion Criteria:

  1. Anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal, targeted therapy, or investigational agents within four weeks or five times of the drug half life, whichever is longer, of the first dose of derazantinib
  2. Major surgery or radiation therapy within four weeks of the first dose of derazantinib
  3. Previous treatment with FGFR inhibitors
  4. History of allergic reactions attributed to compounds of similar chemical or biological composition as derazantinib
  5. Unable or unwilling to swallow the complete daily dose of derazantinib
  6. Clinically unstable central nervous system (CNS) metastasis
  7. History of myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association classification within 6 months of the first dose of derazantinib (MI occurring >6 months of the first dose of derazantinib will be permitted)
  8. Significant GI disorder(s) that could interfere with the absorption, metabolism, or excretion of derazantinib (e.g. Crohn's disease, ulcerative colitis, extensive gastric resection)
  9. History and/or current evidence of clinically relevant ectopic mineralization/calcification
  10. Previous malignancy within 2 years prior to the first dose of derazantinib, except curatively treated non-melanoma skin cancer, carcinoma in-situ of the breast or cervix, or superficial bladder tumors
  11. Known human immunodeficiency virus (HIV) infection
  12. 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.
    • Uncontrolled diabetes mellitus
  13. Blood transfusion within 5 days of the blood draw being used to confirm eligibility
  14. Pregnant or breastfeeding

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): NCT01752920


Locations
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United States, Arizona
Scottsdale Healthcare Research Institute
Scottsdale, Arizona, United States, 85258
United States, Georgia
Emory University, Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Michigan
Karmanos Cancer Institute, Detroit
Detroit, Michigan, United States, 48201
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89169
United States, New York
Montefiore-Einstein Center for Cancer Care
Bronx, New York, United States, 10467
United States, Pennsylvania
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
START - South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, United States, 78229
United States, Washington
University of Washington
Seattle, Washington, United States, 98109
Italy
Istituto Clinico Humanitas
Milan, Italy, 20089
Istituto Nazionale Tumori (National Cancer Institute)
Milan, Italy, 20133
Instituto Oncologico Veneto, IRCCS
Padova, Italy, 35128
Azienda Ospedaliero-Universitaria Pisana - U.O. Oncologia Medica 2 Univ.
Pisa, Italy, 56126
Sponsors and Collaborators
Basilea Pharmaceutica
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Investigators
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Study Director: Marc Engelhardt, MD Basilea Pharmaceutica
  Study Documents (Full-Text)

Documents provided by Basilea Pharmaceutica:
Study Protocol  [PDF] April 10, 2015
Statistical Analysis Plan  [PDF] June 15, 2018

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Basilea Pharmaceutica
ClinicalTrials.gov Identifier: NCT01752920    
Other Study ID Numbers: ARQ 087-101
First Posted: December 19, 2012    Key Record Dates
Results First Posted: October 28, 2021
Last Update Posted: March 9, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by Basilea Pharmaceutica:
FGFR
ARQ 087
Targeted therapy
Molecular therapy
Tyrosine kinase inhibitor
TKI
Receptor tyrosine kinase
RTK
Biomarker
Phase 1
Phase I
Solid tumor
Liver Cancer
Hepatobiliary carcinoma
Biliary tract cancer
Cholangiocarcinoma
Intrahepatic cholangiocarcinoma
FGFR inhibitor
Targeted FGFR kinase inhibitor
Pan-FGFR inhibitor
Selective FGFR inhibitor
FGFR pathway
FGFR signaling
Fibroblast growth factor
FGFR1
FGFR2
FGFR3
FGFR4
FGF
FGF19
Additional relevant MeSH terms:
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Cholangiocarcinoma
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type