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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

Tracking Information
First Submitted Date  ICMJE December 14, 2012
First Posted Date  ICMJE December 19, 2012
Results First Submitted Date  ICMJE August 23, 2021
Results First Posted Date  ICMJE October 28, 2021
Last Update Posted Date March 9, 2022
Actual Study Start Date  ICMJE December 10, 2012
Actual Primary Completion Date August 28, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 30, 2021)
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)
Original Primary Outcome Measures  ICMJE
 (submitted: December 17, 2012)
Assess the safety and tolerability of ARQ 087 in subjects with advanced solid tumors by monitoring frequency and severity of adverse events [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 30, 2021)
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2012)
  • Assess the pharmacokinetic profile (Area under the curve) of ARQ 087 [ Time Frame: During the first 28 days of treatment for each dose level ]
    Blood sampling to assess the pharmokinetic profile (Area under the curve) of ARQ 087.
  • Assess pharmacodynamic activity [ Time Frame: Up to treatment discontinuation ]
    Blood sampling to provide information on tumor FGFR protein expression using immunohistochemistry (IHC).
  • Determine preliminary evidence of activity as defined by standard imaging assessments [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]
  • Determine recommended Phase 2 dose [ Time Frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 4 to 24 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1/2 Study of Derazantinib (ARQ 087) in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE
  • Drug: Derazantinib low dose range
    Derazantinib was administered orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule.
  • Drug: Derazantinib middle dose range
    Derazantinib was administered orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule.
  • Drug: Derazantinib high dose range
    Derazantinib was administered orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule.
  • 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.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Derazantinib low dose range
  • 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.
    Intervention: Drug: Derazantinib middle dose range
  • 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.
    Intervention: Drug: Derazantinib high dose range
  • 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.
    Intervention: Drug: Derazantinib at recommended phase 2 dose (RP2D)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 21, 2019)
119
Original Estimated Enrollment  ICMJE
 (submitted: December 17, 2012)
60
Actual Study Completion Date  ICMJE August 28, 2018
Actual Primary Completion Date August 28, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01752920
Other Study ID Numbers  ICMJE ARQ 087-101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Basilea Pharmaceutica
Original Responsible Party ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Current Study Sponsor  ICMJE Basilea Pharmaceutica
Original Study Sponsor  ICMJE ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Collaborators  ICMJE ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Investigators  ICMJE
Study Director: Marc Engelhardt, MD Basilea Pharmaceutica
PRS Account Basilea Pharmaceutica
Verification Date March 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP