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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04604132




Registration number
NCT04604132
Ethics application status
Date submitted
21/10/2020
Date registered
27/10/2020

Titles & IDs
Public title
Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma
Scientific 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
Secondary ID [1] 0 0
DZB-CS-202
Universal Trial Number (UTN)
Trial acronym
FIDES-03
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastric Adenocarcinoma 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Derazantinib
Treatment: Drugs - Derazantinib-paclitaxel-ramucirumab combination
Treatment: Drugs - Derazantinib-paclitaxel-ramucirumab combination
Treatment: Drugs - Derazantinib
Treatment: Drugs - Derazantinib

Experimental: Substudy 1: Cohort 1.1 Derazantinib 300 mg once daily - Patients with FGFR2 fusions or amplifications were treated with 300 mg Derazantinib monotherapy once daily

Experimental: Substudy 1: Cohort 1.2 Derazantinib 300 mg once daily - Patients with FGFR1-3 mutations were treated with 300 mg Derazantinib monotherapy once daily

Experimental: Substudy 1: Cohort 1.3 Derazantinib 200 mg twice daily - Patients with FGFR fusions, amplifications or mutations were treated with 200 mg Derazantinib monotherapy twice daily

Experimental: Substudy 2: Derazantinib 200 mg once daily +Paclitaxel+ Ramucirumab - Patients with FGFR fusions, amplifications or mutations were treated with 200 mg Derazantinib once daily in combination with Paclitaxel and Ramucirumab

Experimental: Substudy 2: Derazantinib 300 mg once daily+Paclitaxel+ Ramucirumab - Patients with FGFR fusions, amplifications or mutations were treated with 300 mg Derazantinib once daily combination with Paclitaxel and Ramucirumab


Treatment: Drugs: Derazantinib
Derazantinib was administered orally at a dose of 300 mg once daily as monotherapy in the Substudy 1 (Cohort 1.1).

Treatment: Drugs: Derazantinib-paclitaxel-ramucirumab combination
Derazantinib was administered orally at a dose of 200 mg once daily in combination with paclitaxel and ramucirumab.

Paclitaxel was 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 was administered intravenously at a dose of 8 mg/kg every 2 weeks in combination with paclitaxel.

Treatment: Drugs: Derazantinib-paclitaxel-ramucirumab combination
Derazantinib was administered orally at a dose of 300 mg once daily in combination with paclitaxel and ramucirumab.

Paclitaxel was 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 was administered intravenously at a dose of 8 mg/kg every 2 weeks in combination with paclitaxel.

Treatment: Drugs: Derazantinib
Derazantinib was administered orally at a dose of 200 mg twice daily as monotherapy in the Substudy 1 (Cohort 1.3).

Treatment: Drugs: Derazantinib
Derazantinib was administered orally at a dose of 300 mg once daily as monotherapy in the Substudy 1 (Cohort 1.2).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) in Substudy 1 (in Cohorts 1.1 and 1.2)
Timepoint [1] 0 0
From first dose and up to 18 months
Primary outcome [2] 0 0
Progression-free Survival at 4 Months (PFS4) in Substudy 1 in Cohort 1.3
Timepoint [2] 0 0
From first dose and up to 4 months
Primary outcome [3] 0 0
Recommended Phase 2 Dose (RP2D) in Substudy 2 (Derazantinib-paclitaxel-ramucirumab in Combination)
Timepoint [3] 0 0
From first dose and up to 18 months
Secondary outcome [1] 0 0
ORR in Substudy 1 in Cohort 1.3
Timepoint [1] 0 0
From first dose and up to 9 months
Secondary outcome [2] 0 0
Disease Control Rate (DCR) in Substudy 1: Cohort 1.1, 1.2 and 1.3 and Combined Cohorts
Timepoint [2] 0 0
From first dose and up to 18 months
Secondary outcome [3] 0 0
PFS in Substudy 1 in Cohort 1.3
Timepoint [3] 0 0
From first dose and up to 9 months
Secondary outcome [4] 0 0
Overall Survival (OS) in Substudy 1 in Cohort 1.3
Timepoint [4] 0 0
From first dose and up to 9 months
Secondary outcome [5] 0 0
OS in Substudy 2
Timepoint [5] 0 0
From first dose and up to 15 months
Secondary outcome [6] 0 0
ORR in Substudy 2
Timepoint [6] 0 0
From first dose and up to 15 months
Secondary outcome [7] 0 0
DCR in Substudy 2
Timepoint [7] 0 0
From first dose and up to 15 months
Secondary outcome [8] 0 0
DOR in Substudy 2 (Separate and Combined Cohorts)
Timepoint [8] 0 0
From first dose and up to 15 months
Secondary outcome [9] 0 0
PFS in Substudy 2
Timepoint [9] 0 0
From first dose and up to 15 months
Secondary outcome [10] 0 0
Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs)
Timepoint [10] 0 0
TEAEs defined as AEs which were assessed per patient from the patient's first dose and until 90 days after the last dose, which corresponded up to 19 months

Eligibility
Key inclusion criteria
Main inclusion criteria

Patients meeting all of the inclusion criteria at screening were eligible for enrollment in the study, including:

1. Histologically-confirmed adenocarcinoma of the gastro-esophageal junction or stomach.
2. Negative HER2 status obtained from the most recent available tissue sample.
3. Inoperable recurrent, locally advanced adenocarcinoma or progressing stage IV adenocarcinoma of the gastro-esophageal junction or stomach, and prior anti-tumor treatment as specified for each Substudy. Patients were required to be staged as inoperable at the time of screening in order to avoid interference of any potentially planned surgery with RECIST requirements during the study:

Substudy 1: Patients with radiographically documented disease progression after either standard first- or second-line treatment, and no approved and/or tolerable treatment alternative.

Substudy 2: Patients with radiographically documented disease progression after standard first-line treatment, and per Investigator assessment considered suitable to tolerate the treatment regimen.
4. Eligible FGFRfus/amp/mt positive test result. For Substudy 1 Cohort 1.1, FGFR2fus/amp; for Cohort 1.2, FGFR1-3mt; for Cohort 1.3, FGFRfus/amp/mt. For Substudy 2, FGFRfus/amp/mt.
5. Measurable disease as defined by the Investigator using RECIST 1.1 criteria
6. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
7. Adequate organ functions as indicated by Screening visit laboratory values.

Main exclusion criteria

Patients meeting any of the following exclusion criteria at screening were not eligible to be enrolled in the study:

* Receipt of prior cancer treatment within specific interval periods.
* For patients enrolled in Substudy 1, prior treatment with FGFR inhibitors.
* For patients enrolled in Substudy 2, prior treatment with:

* Taxanes within 6 months prior to randomization
* FGFR inhibitors or pathway-targeting agents
* Anti-VEGF(R) therapeutic antibody or pathway-targeting agents
* Concurrent evidence of clinically significant corneal or retinal disorder likely to increase the risk of eye toxicity, including but not limited to bullous/band keratopathy, keratoconjunctivitis (unless keratoconjunctivitis sicca), corneal abrasion (unless related to trauma), inflammation/ulceration, confirmed by ophthalmological examination.
* History of clinically significant cardiac disorders, including myocardial infarction, or New York Heart Association Class II to IV congestive heart failure, within 6 months of the first dose of study drug, and/or any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months of the first dose of study drug, and/or concurrent and clinically significant abnormalities on ECG at Screening, including QTcF > 450 ms for males or > 460 ms for females (mean values from triplicate ECGs).
* Any unresolved (at the time of Screening) clinically significant CTCAE Grade = 2 toxicity (except for alopecia, Grade = 2 platinum-therapy related neuropathy, or Grade = 2 anemia from previous anti-tumor treatment and/or from medical/surgical procedures/interventions).
* Known central nervous system metastases.
* Severe bacterial, fungal, viral and/or parasitic infections on therapeutic oral or IV medication at the time of first dose of study drug administration.
* Significant gastrointestinal disorders that could interfere with the absorption, metabolism, or excretion of derazantinib.
* History of additional malignancy that was progressing or required active treatment.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/11/2022
Sample size
Target
Accrual to date
Final
47
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Monash Medical Centre Clayton - Clayton
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [3] 0 0
The Alfred Hospital - Prahran
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
Argentina
State/province [3] 0 0
Ciudad Autonoma Buenos Aires
Country [4] 0 0
Argentina
State/province [4] 0 0
Ciudad Autonoma de Buenos Aires
Country [5] 0 0
Belgium
State/province [5] 0 0
Edegem
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Belgium
State/province [7] 0 0
Menen
Country [8] 0 0
Brazil
State/province [8] 0 0
Rio Grande Do Norte
Country [9] 0 0
Brazil
State/province [9] 0 0
Jaú
Country [10] 0 0
Brazil
State/province [10] 0 0
Rio De Janeiro
Country [11] 0 0
Brazil
State/province [11] 0 0
Santo André
Country [12] 0 0
Brazil
State/province [12] 0 0
São José Do Rio Preto
Country [13] 0 0
Chile
State/province [13] 0 0
Region Met
Country [14] 0 0
Chile
State/province [14] 0 0
Santiago
Country [15] 0 0
Chile
State/province [15] 0 0
Temuco
Country [16] 0 0
France
State/province [16] 0 0
Avignon
Country [17] 0 0
France
State/province [17] 0 0
Besancon
Country [18] 0 0
France
State/province [18] 0 0
Dijon
Country [19] 0 0
France
State/province [19] 0 0
Paris
Country [20] 0 0
France
State/province [20] 0 0
Villejuif
Country [21] 0 0
Germany
State/province [21] 0 0
Baden Wuerttemberg
Country [22] 0 0
Germany
State/province [22] 0 0
Niedersachsen
Country [23] 0 0
Germany
State/province [23] 0 0
Sachsen
Country [24] 0 0
Germany
State/province [24] 0 0
Dresden
Country [25] 0 0
Germany
State/province [25] 0 0
Frankfurt
Country [26] 0 0
Germany
State/province [26] 0 0
Mainz
Country [27] 0 0
Italy
State/province [27] 0 0
Bologna
Country [28] 0 0
Italy
State/province [28] 0 0
Catanzaro
Country [29] 0 0
Italy
State/province [29] 0 0
Milano
Country [30] 0 0
Italy
State/province [30] 0 0
Padova
Country [31] 0 0
Italy
State/province [31] 0 0
Rozzano
Country [32] 0 0
Italy
State/province [32] 0 0
Siena
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Goyang-si
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Hwasun
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seongnam
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Seoul
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Suwon
Country [38] 0 0
Poland
State/province [38] 0 0
Skórzewo
Country [39] 0 0
Poland
State/province [39] 0 0
Warszawa
Country [40] 0 0
Poland
State/province [40] 0 0
Lódz
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Kazan
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Moscow
Country [43] 0 0
Russian Federation
State/province [43] 0 0
Omsk
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Pesochnyy
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Saint Petersburg
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Tomsk
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Ufa
Country [48] 0 0
Spain
State/province [48] 0 0
Barcelona
Country [49] 0 0
Spain
State/province [49] 0 0
L'Hospitalet de Llobregat
Country [50] 0 0
Spain
State/province [50] 0 0
Madrid
Country [51] 0 0
Spain
State/province [51] 0 0
Pamplona
Country [52] 0 0
Turkey
State/province [52] 0 0
Adana
Country [53] 0 0
Turkey
State/province [53] 0 0
Ankara
Country [54] 0 0
Turkey
State/province [54] 0 0
Antalya
Country [55] 0 0
Turkey
State/province [55] 0 0
Istanbul
Country [56] 0 0
Turkey
State/province [56] 0 0
Kocaeli
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Cambridge
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Dundee
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Glasgow
Country [60] 0 0
United Kingdom
State/province [60] 0 0
London
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Manchester
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Basilea Pharmaceutica
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Manuel Häckl, MD
Address 0 0
Basilea Pharmaceutica International Ltd, Allschwil
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04604132