Gastric AdenocarcinomaPhase 1/2FIDES-03NCT04604132
Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma
A Phase 1/2 study testing Derazantinib and Derazantinib-paclitaxel-ramucirumab combination in people with Gastric Adenocarcinoma, run by Basilea Pharmaceutica at 81 sites in 15 countries.
Trial summary
The purpose of this study was to evaluate the efficacy of derazantinib monotherapy or derazantinib in combination with paclitaxel and ramucirumab in patients with gastric adenocarcinoma (GAC) i.e. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Adenocarcinoma
- What is being tested?
- Derazantinib and Derazantinib-paclitaxel-ramucirumab combination
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 81 sitesin 15 countries
- Study dates
- 6 Oct 2020to 21 Nov 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Main inclusion criteria
Patients meeting all of the inclusion criteria at screening were eligible for enrollment in the study, including:
- Histologically-confirmed adenocarcinoma of the gastro-esophageal junction or stomach.
- 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 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.
- 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.
- Measurable disease as defined by the Investigator using RECIST 1.1 criteria
- Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
- 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.
Trial locations and contacts
81 sites in 15 countries.
81 sites in 15 countries
Russia9 sites
SAIH "Republican Clinical Oncological Dispensary of the Ministry of Healthcare of Republic Tatarstan
Kazan', 420029
FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
Moscow, 115478
"VitaMed" LLC
Moscow, 121309
BHI of Omsk region "Clinical Oncology Dispensary"
Omsk, 644013
FSBI "Clinical Research and Practical Center for specialized medical care (oncology)"
Pesochnyy, 197758
Pavlov First Saint Petersburg State Medical University
Saint Petersburg, 197022
FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
Saint Petersburg, 197758
Tomsk Research Instutite of Oncology
Tomsk, 634045
SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
Ufa, 450054
Italy8 sites
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
Bologna, 40138
Azienda Ospedaliero Universitaria Mater Domini
Catanzaro, 88100
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
IEO Istituto Europeo di Oncologia
Milan, 20141
Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
Milan, 20162
IOV - Istituto Oncologico Veneto IRCCS
Padova, 35128
Istituto Clinico Humanitas
Rozzano, 20089
A.O.U. Senese Policlinico Santa Maria alle Scotte
Siena, 53100
South Korea8 sites
National Cancer Center
Goyang-si, 10408
Chonnam National University Hwasun Hospital
Hwasun, 58128
Seoul National University Bundang Hospital
Seongnam, 13620
Seoul National University Hospital
Seoul, 03080
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 06591
Ajou University Hospital
Suwon, 16499
Spain8 sites
Hospital del Mar
Barcelona, 08003
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Clinic de Barcelona
Barcelona, 08036
ICO l'Hospitalet - Hospital Duran i Reynals
L'Hospitalet de Llobregat, 08908
MD Anderson Cancer Centre
Madrid, 28033
Hospital Universitario Ramon y Cajal
Madrid, 28034
Centro Integral Oncologico Clara Campal
Madrid, 28050
Clinica Universidad de Navarra
Pamplona, 31008
Turkey (Türkiye)8 sites
Baskent University Adana Application and Research Center
Adana, 01220
Hacettepe University Medical Faculty
Ankara, 06100
Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
Ankara, 06105
Ankara City Hospital
Ankara, 06800
Akdeniz University Medical Faculty
Antalya, 07058
Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
Istanbul, 34098
Istanbul Medeniyet Uni Goztepe Training&Res Hosp
Istanbul, 34854
Kocaeli Universitesi Tip Fakultesi
Kocaeli, 41380
France6 sites
Institut Sainte Catherine
Avignon, 84918
CHU Besançon - Hôpital Jean Minjoz
Besançon, 25030
Centre Georges François Leclerc
Dijon, 21079
Hôpital Saint-Louis
Paris, 75475
Hôpital Saint-Antoine
Paris, 75571
Institut Gustave Roussy
Villejuif, 94805
Germany6 sites
Universitaetsklinikum Carl Gustav Carus TU Dresden
Dresden, Saxony, 01307
Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt
Dresden, 01067
Krankenhaus Nordwest GmbH
Frankfurt, 60488
Medizinische Hochschule Hannover
Hanover, Lower Saxony, 30625
Uniklinik Mainz
Mainz, 55131
Universitaetsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081
United Kingdom6 sites
Addenbrooke's Hospital
Cambridge, CB2 0QQ
Ninewells Hospital
Dundee, DD1 9SY
Beatson West of Scotland Cancer Centre
Glasgow, G12 OYN
University College London Hospitals
London, W1T7HA
The Christie
Manchester, M20 4BX
Royal Marsden Hospital- Sutton
Sutton, SM2 5PT
Brazil5 sites
Fundação Doutor Amaral Carvalho
Jaú, 17210-120
Liga Norte-Rio-Grandense Contra o Câncer
Natal, Rio Grande do Norte, 59075-740
Instituto Nacional de Câncer José Alencar Gomes da Silva
Rio de Janeiro, 20230-230
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
Santo André, 09060-870
Fundação Faculdade Regional de Medicina de São José do Rio Preto
São José do Rio Preto, 15090-000
Poland4 sites
Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna
Lodz, 90-242
Examen sp. z o.o.
Skórzewo, 60-185
Centrum Zdrowia MDM
Warsaw, 01-401
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
Warsaw, 02-781
Australia3 sites
Monash Medical Centre Clayton
Clayton, 3168
Peter MacCallum Cancer Centre
Melbourne, 3000
The Alfred Hospital
Prahran, 3181
Chile3 sites
CeCim Biocinetic
Santiago, Region Met, 8331143
Centro de Estudios Clínicos SAGA
Santiago, 7500000
Instituto Clinico Oncologico
Temuco, 4810469
United States2 sites
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
AdventHealth Cancer Institute
Orlando, Florida, 32806
Argentina2 sites
Fundación Favaloro para la Docencia e Investigación Médica
Buenos Aires, C1093AAS
Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo
Ciudad Autonoma Buenos Aires, B1264AAA
About this study
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
The purpose of this study was to evaluate the efficacy of derazantinib monotherapy or derazantinib in combination with paclitaxel and ramucirumab in patients with gastric adenocarcinoma (GAC) i.e. with human epidermal growth factor receptor 2 (HER2)-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring fibroblast growth factor receptor 2 (FGFR2) genetic aberrations (GA).
Read the detailed description
The study comprised two 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.
In Substudy 1, GAC patients with specified FGFR GAs, after either first- or second-line treatment, and no approved treatment alternative were treated with derazantinib 300 mg once daily or 200 mg twice daily, with the aim of evaluating the safety, tolerability, and efficacy of derazantinib monotherapy in this patient population.
In Substudy 2, GAC patients with specified FGFR GAs after standard first-line treatment, were treated with a derazantinib-paclitaxel-ramucirumab combination with the aim of evaluating the safety, tolerability, and efficacy of the combination therapy and determining the recommended phase 2 dose (RP2D).
The study originally planned to include three substudies but was prematurely terminated for administrative reasons before the third substudy (including combination therapy with derazantinib plus atezolizumab) was initiated.
- Conditions
- Gastric Adenocarcinoma
- Being tested
- Derazantinib, Derazantinib-paclitaxel-ramucirumab combination
- Keywords
- 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
- Medical subject headings
- Stomach Neoplasms, Acrocephalosyndactylia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DerazantinibDrug
Derazantinib was administered orally at a dose of 300 mg once daily as monotherapy in the Substudy 1 (Cohort 1.1).
Derazantinib-paclitaxel-ramucirumab combinationDrug
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.
Derazantinib-paclitaxel-ramucirumab combinationDrug
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.
DerazantinibDrug
Derazantinib was administered orally at a dose of 200 mg twice daily as monotherapy in the Substudy 1 (Cohort 1.3).
DerazantinibDrug
Derazantinib was administered orally at a dose of 300 mg once daily as monotherapy in the Substudy 1 (Cohort 1.2).
| Study group | Role | What they receive |
|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg once daily | Experimental | Patients with FGFR2 fusions or amplifications were treated with 300 mg Derazantinib monotherapy once daily Receives: Drug: Derazantinib |
| Substudy 1: Cohort 1.2 Derazantinib 300 mg once daily | Experimental | Patients with FGFR1-3 mutations were treated with 300 mg Derazantinib monotherapy once daily Receives: Drug: Derazantinib |
| Substudy 1: Cohort 1.3 Derazantinib 200 mg twice daily | Experimental | Patients with FGFR fusions, amplifications or mutations were treated with 200 mg Derazantinib monotherapy twice daily Receives: Drug: Derazantinib |
| Substudy 2: Derazantinib 200 mg once daily +Paclitaxel+ Ramucirumab | Experimental | Patients with FGFR fusions, amplifications or mutations were treated with 200 mg Derazantinib once daily in combination with Paclitaxel and Ramucirumab Receives: Drug: Derazantinib-paclitaxel-ramucirumab combination |
| Substudy 2: Derazantinib 300 mg once daily+Paclitaxel+ Ramucirumab | Experimental | Patients with FGFR fusions, amplifications or mutations were treated with 300 mg Derazantinib once daily combination with Paclitaxel and Ramucirumab Receives: Drug: Derazantinib-paclitaxel-ramucirumab combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) in Substudy 1 (in Cohorts 1.1 and 1.2)
ORR was defined by the percentage of patients with confirmed complete response (CR, which means disappearance of all target lesions) or partial response (PR, which means >=30% decrease in the sum of the longest diameter of target lesions) by blinded independent central review (BICR) using the internationally recognized criteria for the radiological assessment in tumor response of solid tumors (RECIST 1.1). Overall Response (OR) = CR + PR.
The patients in Cohort 1.1 had FGFR2 fusions or amplification gastric adenocarcinoma (GAC) and FGFR1-3 mutations GAC in Cohort 1.2.
Measured: From first dose and up to 18 months
Progression-free Survival at 4 Months (PFS4) in Substudy 1 in Cohort 1.3
PFS4 was defined by the percentage of patients alive and free of disease progression (defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions) by BICR per RECIST. 1.1. Patients in this Cohort had FGFR fusions, amplifications or mutations GAC
Measured: From first dose and up to 4 months
Recommended Phase 2 Dose (RP2D) in Substudy 2 (Derazantinib-paclitaxel-ramucirumab in Combination)
RP2D was 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 derazantinib-paclitaxel-ramucirumab combination in patients with FGFR fusions, amplifications or mutations GAC.
Measured: From first dose and up to 18 months
Secondary outcomes (10)
ORR in Substudy 1 in Cohort 1.3
ORR was defined by the percentage of patients with CR or PR by BICR according to RECIST Version 1.1.
Measured: From first dose and up to 9 months
Disease Control Rate (DCR) in Substudy 1: Cohort 1.1, 1.2 and 1.3 and Combined Cohorts
Defined as the percentage of patients with confirmed CR, PR or stable disease (SD) by BICR per RECIST version 1.1.
Measured: From first dose and up to 18 months
PFS in Substudy 1 in Cohort 1.3
PFS was calculated from patient enrollment to progressive disease (PD) date by BICR per RECIST version 1.1
Measured: From first dose and up to 9 months
Overall Survival (OS) in Substudy 1 in Cohort 1.3
OS was measured from patient enrollment to time of death.
Measured: From first dose and up to 9 months
OS in Substudy 2
OS was measured from patient enrollment to time of death
Measured: From first dose and up to 15 months
ORR in Substudy 2
ORR was defined by the percentage of patients with CR or PR by BICR per RECIST version 1.1.
Measured: From first dose and up to 15 months
DCR in Substudy 2
Defined as the percentage of patients with confirmed CR, PR or SD by BICR per RECIST version 1.1.
Measured: From first dose and up to 15 months
DOR in Substudy 2 (Separate and Combined Cohorts)
DOR was calculated from the first date of documented tumor response to disease progression by BICR per RECIST version 1.1 (or death if no documentation of PD is obtained).
Measured: From first dose and up to 15 months
PFS in Substudy 2
PFS was calculated from patient enrollment to progressive disease (PD) date by BICR per RECIST version 1.1.
Measured: From first dose and up to 15 months
Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs)
Number of patients experiencing TEAE of Grade 3 and above according to Common Terminology Criteria for Adverse Events (CTCAE). CTCAE are a set of criteria for the standardized classification of TEAEs of drugs used in cancer therapy. It uses a range of grades from 1 to 5 describing increasing levels of severity of the TEAEs.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2020
- Study start6 Oct 2020
- Primary completion21 Nov 2022
- Study completion21 Nov 2022
Why it stopped: Terminated prematurely for administrative reasons not related to patient safety.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gastric AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Basilea Pharmaceutica
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Manuel Häckl, MD, Study director, Basilea Pharmaceutica International Ltd, Allschwil
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04604132
- Sponsor's protocol ID
- DZB-CS-202
- Acronym
- FIDES-03
- Status last verified
- Mar 2024
- First submitted
- 21 Oct 2020
- Last updated
- 4 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04604132
- Acronym / sponsor ID
- FIDES-03 / DZB-CS-202
- Conditions
- Gastric Adenocarcinoma
- Keywords
- gastric cancer, gastro-esophageal adenocarcinoma, adenocarcinoma of the stomach or gastro-esophageal junction, fibroblast growth factor receptor, FGFR genetic aberration, targeted therapy, derazantinib, atezolizumab
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated prematurely for administrative reasons not related to patient safety.
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Basilea PharmaceuticaIndustry (pharma, biotech, devices)
- Study start
- 6 Oct 2020 (actual)
- Primary completion
- 21 Nov 2022 (actual)
- Study completion
- 21 Nov 2022 (actual)
- First posted
- 27 Oct 2020 (actual)
- Results
- Posted 4 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to evaluate the efficacy of derazantinib monotherapy or derazantinib in combination with paclitaxel and ramucirumab in patients with gastric adenocarcinoma (GAC) i.e. with human epidermal growth factor receptor 2 (HER2)-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring fibroblast growth factor receptor 2 (FGFR2) genetic aberrations (GA).
Detailed description
The study comprised two 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.
In Substudy 1, GAC patients with specified FGFR GAs, after either first- or second-line treatment, and no approved treatment alternative were treated with derazantinib 300 mg once daily or 200 mg twice daily, with the aim of evaluating the safety, tolerability, and efficacy of derazantinib monotherapy in this patient population.
In Substudy 2, GAC patients with specified FGFR GAs after standard first-line treatment, were treated with a derazantinib-paclitaxel-ramucirumab combination with the aim of evaluating the safety, tolerability, and efficacy of the combination therapy and determining the recommended phase 2 dose (RP2D).
The study originally planned to include three substudies but was prematurely terminated for administrative reasons before the third substudy (including combination therapy with derazantinib plus atezolizumab) was initiated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Substudy 1: Cohort 1.1 Derazantinib 300 mg once daily | Experimental | Drug: DerazantinibPatients with FGFR2 fusions or amplifications were treated with 300 mg Derazantinib monotherapy once daily |
| Substudy 1: Cohort 1.2 Derazantinib 300 mg once daily | Experimental | Drug: DerazantinibPatients with FGFR1-3 mutations were treated with 300 mg Derazantinib monotherapy once daily |
| Substudy 1: Cohort 1.3 Derazantinib 200 mg twice daily | Experimental | Drug: DerazantinibPatients with FGFR fusions, amplifications or mutations were treated with 200 mg Derazantinib monotherapy twice daily |
| Substudy 2: Derazantinib 200 mg once daily +Paclitaxel+ Ramucirumab | Experimental | Drug: Derazantinib-paclitaxel-ramucirumab combinationPatients with FGFR fusions, amplifications or mutations were treated with 200 mg Derazantinib once daily in combination with Paclitaxel and Ramucirumab |
| Substudy 2: Derazantinib 300 mg once daily+Paclitaxel+ Ramucirumab | Experimental | Drug: Derazantinib-paclitaxel-ramucirumab combinationPatients with FGFR fusions, amplifications or mutations were treated with 300 mg Derazantinib once daily combination with Paclitaxel and Ramucirumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DerazantinibDerazantinib was administered orally at a dose of 300 mg once daily as monotherapy in the Substudy 1 (Cohort 1.1). | Drug | Substudy 1: Cohort 1.1 Derazantinib 300 mg once daily |
| Derazantinib-paclitaxel-ramucirumab combinationDerazantinib 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. | Drug | Substudy 2: Derazantinib 200 mg once daily +Paclitaxel+ Ramucirumab |
| Derazantinib-paclitaxel-ramucirumab combinationDerazantinib 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. | Drug | Substudy 2: Derazantinib 300 mg once daily+Paclitaxel+ Ramucirumab |
| DerazantinibDerazantinib was administered orally at a dose of 200 mg twice daily as monotherapy in the Substudy 1 (Cohort 1.3). | Drug | Substudy 1: Cohort 1.3 Derazantinib 200 mg twice daily |
| DerazantinibDerazantinib was administered orally at a dose of 300 mg once daily as monotherapy in the Substudy 1 (Cohort 1.2). | Drug | Substudy 1: Cohort 1.2 Derazantinib 300 mg once daily |
Primary outcome
Objective Response Rate (ORR) in Substudy 1 (in Cohorts 1.1 and 1.2)
Time frame: From first dose and up to 18 months
ORR was defined by the percentage of patients with confirmed complete response (CR, which means disappearance of all target lesions) or partial response (PR, which means >=30% decrease in the sum of the longest diameter of target lesions) by blinded independent central review (BICR) using the internationally recognized criteria for the radiological assessment in tumor response of solid tumors (RECIST 1.1). Overall Response (OR) = CR + PR. The patients in Cohort 1.1 had FGFR2 fusions or amplification gastric adenocarcinoma (GAC) and FGFR1-3 mutations GAC in Cohort 1.2.
Progression-free Survival at 4 Months (PFS4) in Substudy 1 in Cohort 1.3
Time frame: From first dose and up to 4 months
PFS4 was defined by the percentage of patients alive and free of disease progression (defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions) by BICR per RECIST. 1.1. Patients in this Cohort had FGFR fusions, amplifications or mutations GAC
Recommended Phase 2 Dose (RP2D) in Substudy 2 (Derazantinib-paclitaxel-ramucirumab in Combination)
Time frame: From first dose and up to 18 months
RP2D was 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 derazantinib-paclitaxel-ramucirumab combination in patients with FGFR fusions, amplifications or mutations GAC.
10 secondary outcomes
ORR in Substudy 1 in Cohort 1.3
Time frame: From first dose and up to 9 months
Disease Control Rate (DCR) in Substudy 1: Cohort 1.1, 1.2 and 1.3 and Combined Cohorts
Time frame: From first dose and up to 18 months
PFS in Substudy 1 in Cohort 1.3
Time frame: From first dose and up to 9 months
Overall Survival (OS) in Substudy 1 in Cohort 1.3
Time frame: From first dose and up to 9 months
OS in Substudy 2
Time frame: From first dose and up to 15 months
ORR in Substudy 2
Time frame: From first dose and up to 15 months
DCR in Substudy 2
Time frame: From first dose and up to 15 months
DOR in Substudy 2 (Separate and Combined Cohorts)
Time frame: From first dose and up to 15 months
PFS in Substudy 2
Time frame: From first dose and up to 15 months
Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs)
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manuel Häckl, MD study director
Basilea Pharmaceutica International Ltd, Allschwil
81 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Derazantinib and Derazantinib-paclitaxel-ramucirumab combination in people with Gastric Adenocarcinoma, run by Basilea Pharmaceutica at 81 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 81 sites in Russia, Italy, South Korea, Spain, Turkey (Türkiye) and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) in Substudy 1 (in Cohorts 1.1 and 1.2) (time frame: From first dose and up to 18 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2024.