Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04604132
Recruitment Status : Recruiting
First Posted : October 27, 2020
Last Update Posted : July 9, 2021
Sponsor:
Information provided by (Responsible Party):
Basilea Pharmaceutica

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).

Condition or disease Intervention/treatment Phase
Gastric Adenocarcinoma Drug: Derazantinib Drug: Derazantinib-paclitaxel-ramucirumab Drug: Derazantinib-atezolizumab Drug: Paclitaxel-ramucirumab Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 254 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 6, 2020
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : July 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Derazantinib
Derazantinib will be administered orally at a dose of 300 mg once a day as monotherapy.

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.
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.


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.
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.


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.
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.





Primary Outcome Measures :
  1. 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).

  2. 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.


Secondary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: Approximately 2 years ]
    PFS will be measured from patient enrollment to progressive disease (PD) date by BICR

  2. 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

  3. 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)

  4. Overall Survival (OS) [ Time Frame: Approximately 2 years ]
    OS will be measured from patient enrollment to time of death



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  • For Substudies 1 and 3, 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
    6. 28 days of 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
  • For Substudies 1 and 3, known CNS metastases
  • Concurrent uncontrolled or active infection with human immunodeficiency virus (HIV; known HIV 1/2 antibodies positive); active hepatitis B virus (HBV) and 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)

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): NCT04604132


Contacts
Layout table for location contacts
Contact: Inessa Polyakova, MD +41 76 682 3147 inessa.polyakova@basilea.com
Contact: Stephan Braun, MD +41 79 121 1561 stephan.braun@basilea.com

Locations
Show Show 69 study locations
Sponsors and Collaborators
Basilea Pharmaceutica
Investigators
Layout table for investigator information
Study Director: Inessa Polyakova, MD Basilea Pharmaceutica International Ltd
Layout table for additonal information
Responsible Party: Basilea Pharmaceutica
ClinicalTrials.gov Identifier: NCT04604132    
Other Study ID Numbers: DZB-CS-202
First Posted: October 27, 2020    Key Record Dates
Last Update Posted: July 9, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Basilea Pharmaceutica:
gastric cancer
gastro-esophageal adenocarcinoma
adenocarcinoma of the stomach or gastro-esophageal junction
fibroblast growth factor receptor
FGFR genetic aberration
targeted therapy
derazantinib
atezolizumab
Tecentriq
paclitaxel
ramucirumab
Cyramza
solid tumor
Additional relevant MeSH terms:
Layout table for MeSH terms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Atezolizumab
Ramucirumab
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs