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Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma (FIDES-03)

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ClinicalTrials.gov Identifier: NCT04604132
Recruitment Status : Recruiting
First Posted : October 27, 2020
Last Update Posted : March 8, 2022
Sponsor:
Information provided by (Responsible Party):
Basilea Pharmaceutica

Tracking Information
First Submitted Date  ICMJE October 21, 2020
First Posted Date  ICMJE October 27, 2020
Last Update Posted Date March 8, 2022
Actual Study Start Date  ICMJE October 6, 2020
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 13, 2021)
  • Objective response rate (ORR) per RECIST 1.1 in Substudy 1 (in two subgroups Cohort 1.1 and 1.2) and Substudy 3) [ Time Frame: Approximately 30 months ]
    ORR will be measured by the proportion of patients with confirmed complete response (CR) or partial response (PR) by blinded independent central review (BICR).
  • 4-month progression-free survival rate (PFS4, in a subgroup (Cohort 1.3) within Substudy 1) [ Time Frame: Approximately 18 months ]
    PFS4 will be measured by the proportion of patients alive and free of disease progression by blinded independent central review (BICR) per RECIST. 1.1
  • Recommended phase 2 dose (RP2D) of derazantinib-paclitaxel-ramucirumab in combination (Substudy 2) [ Time Frame: Approximately 18 months ]
    RP2D will be determined from safety and tolerability according to the aggregate of dose-limiting toxicity criteria and adverse event (AE) data, and considering further pharmacokinetic and efficacy data of the combination.
Original Primary Outcome Measures  ICMJE
 (submitted: October 21, 2020)
  • Overall response rate (ORR) per RECIST 1.1 (Substudies 1 and 3) [ Time Frame: Approximately 30 months ]
    ORR of will be measured by the proportion of patients with confirmed complete response (CR) or partial response (PR) by blinded independent central review (BICR).
  • Recommended phase 2 dose (RP2D) of derazantinib-paclitaxel-ramucirumab in combination (Substudy 2) [ Time Frame: Approximately 8 months ]
    RP2D will be determined from safety and tolerability according to the aggregate of dose-limiting toxicity criteria and adverse event (AE) data, and considering further pharmacokinetic and efficacy data of the combination.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2021)
  • ORR per RECIST 1.1 in subgroup Cohort 1.3 within Substudy 1and in Substudy 3 [ Time Frame: Approximately 24 months ]
    ORR will be measured by the proportion of patients with confirmed complete response (CR) or partial response (PR) by blinded independent central review (BICR).
  • Disease Control Rate (DCR) [ Time Frame: Approximately 24 months ]
    Measured by the proportion of patients with confirmed CR, PR or stable disease (SD) by BICR
  • Duration of Response (DOR) [ Time Frame: Approximately 24 months ]
    DOR will be calculated from the first date of documented tumor response to disease progression by BICR (or death if no documentation of PD is obtained)
  • Progression-free Survival (PFS) [ Time Frame: Approximately 24 months ]
    PFS will be measured from patient enrollment to progressive disease (PD) date by BICR
  • Overall Survival (OS) [ Time Frame: Approximately 24 months ]
    OS will be measured from patient enrollment to time of death
  • Pharmacokinetic (PK) profile: Peak Plasma Concentration (Cmax) of derazantinib 200 mg twice daily monotherapy [ Time Frame: Approximately 24 months ]
    Derazantinib plasma concentrations including Cmax will be assessed by measurements in plasma samples
  • Pharmacokinetic (PK) profile: Area under the plasma concentration versus time curve (AUC) of derazantinib 200 mg twice daily monotherapy [ Time Frame: Approximately 24 months ]
    AUC will be assessed by measurements of derazantinib in plasma samples
  • Pharmacokinetic (PK) profile: The time to reach Cmax (Tmax) of derazantinib 200 mg twice daily monotherapy [ Time Frame: Approximately 24 months ]
    Tmax will be assessed by measurements of derazantinib in plasma samples
Original Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2020)
  • Progression-free Survival (PFS) [ Time Frame: Approximately 2 years ]
    PFS will be measured from patient enrollment to progressive disease (PD) date by BICR
  • Disease Control Rate (DCR) [ Time Frame: Approximately 2 years ]
    Measured by the proportion of patients with confirmed CR, PR or stable disease (SD) by BICR
  • Duration of Response (DOR) [ Time Frame: Approximately 2 years ]
    DOR will be calculated from the first date of documented tumor response to disease progression by BICR (or death if no documentation of PD is obtained)
  • Overall Survival (OS) [ Time Frame: Approximately 2 years ]
    OS will be measured from patient enrollment to time of death
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma
Official Title  ICMJE A Phase 1b/2 Study of Derazantinib as Monotherapy and Combination Therapy With Paclitaxel, Ramucirumab or Atezolizumab in Patients With HER2-negative Gastric Adenocarcinoma Expressing FGFR2 Genetic Aberrations
Brief Summary The purpose of this study is to evaluate the efficacy of derazantinib monotherapy or derazantinib in combination with paclitaxel, ramucirumab, or atezolizumab in patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR2 genetic aberrations (GA).
Detailed Description The study comprises three open-label substudies in patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR2 gene translocations, FGFR2 gene amplifications, or FGFR1-3 mutations. Patients will be treated with single-agent derazantinib or derazantinib in combination with paclitaxel, ramucirumab, or atezolizumab. The study enrolls patients with either metastatic or recurrent locally advanced HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction inoperable at the time of screening, and radiologically confirmed disease progression after one or at least one standard treatment regimen.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Gastric Adenocarcinoma
Intervention  ICMJE
  • Drug: Derazantinib
    Derazantinib will be administered orally at a dose of 300 mg once a day and at a dose of 200 mg twice daily as monotherapy in the Substudy 1.
  • Drug: Derazantinib-paclitaxel-ramucirumab

    Derazantinib will be administered at the RP2D for derazantinib-paclitaxel-ramucirumab determined in Substudy 2 in combination with paclitaxel and ramucirumab.

    Paclitaxel will be administered intravenously at the RP2D for derazantinib-paclitaxel-ramucirumab determined in Substudy 2 on days 1, 8, and 15 of a 28-day cycle in combination with derazantinib and ramucirumab.

    Ramucirumab will be administered intravenously at the RP2D for derazantinib-paclitaxel-ramucirumab determined in Substudy 2 every 2 weeks in combination with derazantinib and paclitaxel.

  • Drug: Derazantinib-atezolizumab

    Derazantinib will be administered orally at a dose of 300 mg once a day in combination with atezolizumab.

    Atezolizumab will be administered intravenously at a dose of 1200 mg every 3 weeks in combination with derazantinib.

  • Drug: Paclitaxel-ramucirumab

    Paclitaxel will be administered intravenously at a dose of 80 mg/m² on days 1, 8, and 15 of a 28-day cycle in combination with ramucirumab.

    Ramucirumab will be administered intravenously at a dose of 8 mg/kg every 2 weeks in combination with paclitaxel.

Study Arms  ICMJE
  • Experimental: Derazantinib
    In Substudies 1 and 3.1, patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR genetic aberrations will receive derazantinib.
    Intervention: Drug: Derazantinib
  • Experimental: Derazantinib-paclitaxel-ramucirumab
    In Substudies 2 and 3.2, patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR genetic aberrations will receive derazantinib-paclitaxel-ramucirumab in combination.
    Intervention: Drug: Derazantinib-paclitaxel-ramucirumab
  • Experimental: Derazantinib-atezolizumab
    In Substudy 3.3, patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR genetic aberrations will receive derazantinib-atezolizumab in combination.
    Intervention: Drug: Derazantinib-atezolizumab
  • Active Comparator: Standard of care
    In Substudy 3.4, patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR genetic aberrations will receive the Standard of Care drugs paclitaxel-ramucirumab in combination.
    Intervention: Drug: Paclitaxel-ramucirumab
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 21, 2020)
254
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2023
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Histologically-confirmed adenocarcinoma of the gastro-esophageal junction or stomach
  • Male or female aged ≥ 18 years
  • Negative HER2 status obtained from the most recent available tissue sample
  • Inoperable recurrent, locally advanced adenocarcinoma or progressing stage IV adenocarcinoma of the gastro-esophageal junction or stomach, and disease progression after either standard first- or second-line treatment (Substudy 1), or after standard first-line treatment (Substudies 2 and 3)
  • Positive test for eligible FGFR aberrations (FGFR2 fusions / rearrangements / amplifications; FGFR1, FGFR2, or FGFR3 mutations / short variants)
  • Measurable disease as defined by the Investigator using RECIST 1.1 criteria
  • ECOG PS of 0 or 1
  • Men and women of childbearing potential must agree to avoid impregnating a partner or becoming pregnant, respectively, during the study, and for at least 150 days after the last dose of either investigational drug

Key Exclusion Criteria:

  • Prior anticancer or investigational drug treatment within an interval shorter than the following, as applicable:

    1. One chemotherapy or biological (e.g., antibody) cycle interval
    2. Five half-lives of any small molecule investigational or licensed medicinal product
    3. Two weeks, for any investigational medicinal product with an unknown half-life
    4. Four weeks of curative radiotherapy
    5. Seven days of palliative radiotherapy
  • Prior treatment with FGFR Inhibitors (all substudies), and prior treatment with taxanes within 6 months prior to randomization and/or anti-VEGF(R) therapeutic antibody or pathway-targeting agents (Substudies 2 and 3), and prior treatment with anti-programmed cell death receptor-1 (PD-1) or anti-programmed death ligand-1 (PD-L1) therapeutic antibody or pathway-targeting agents (Substudy 3)
  • Concurrent evidence of clinically significant corneal or retinal disorder
  • History of clinically significant cardiac disorders and/or a QT interval corrected by Fridericia's formula (QTcF) > 450 ms for males or > 460 ms for females
  • Known CNS metastases
  • Concurrent uncontrolled or active infection with human immunodeficiency virus (HIV; known HIV 1/2 antibodies positive); active or chronic hepatitis B without current antiviral therapy and an HBV DNA ≥ 100 IU/mL virus (HBV); active hepatitis C virus (HCV) co-infection; active tuberculosis (for Substudies 2 and 3)
  • Child-Pugh B or C liver cirrhosis, or a history of hepatic encephalopathy, hepatorenal syndrome, or clinically-meaningful ascites related to cirrhosis (for Substudies 2 and 3)
  • Administration of a live, attenuated vaccine within 30 days prior to randomization (for Substudy 3)
  • Treatment with systemic corticosteroids (except for steroidal replacement therapy) or other systemic immunosuppressive medications within 2 weeks prior to first dose of study drug or anticipated requirement for systemic immunosuppressive medications during the study (for Substudy 3)
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: Inessa Polyakova, MD +41 76 682 3147 inessa.polyakova@basilea.com
Contact: Marc Engelhardt, MD +41 61 567 15 46 marc.engelhardt@basilea.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Chile,   France,   Germany,   Italy,   Korea, Republic of,   Poland,   Russian Federation,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04604132
Other Study ID Numbers  ICMJE DZB-CS-202
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Basilea Pharmaceutica
Study Sponsor  ICMJE Basilea Pharmaceutica
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Inessa Polyakova, MD Basilea Pharmaceutica International Ltd
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