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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04604132
Other study ID # DZB-CS-202
Secondary ID
Status Terminated
Phase Phase 1/Phase 2
First received
Last updated
Start date October 6, 2020
Est. completion date November 21, 2022

Study information

Verified date March 2024
Source Basilea Pharmaceutica
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. 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).


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.


Recruitment information / eligibility

Status Terminated
Enrollment 47
Est. completion date November 21, 2022
Est. primary completion date November 21, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Derazantinib
Derazantinib was administered orally at a dose of 300 mg once daily as monotherapy in the Substudy 1 (Cohort 1.1).
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.
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.
Derazantinib
Derazantinib was administered orally at a dose of 200 mg twice daily as monotherapy in the Substudy 1 (Cohort 1.3).
Derazantinib
Derazantinib was administered orally at a dose of 300 mg once daily as monotherapy in the Substudy 1 (Cohort 1.2).

Locations

Country Name City State
Argentina Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo Ciudad Autonoma Buenos Aires
Argentina Fundación Favaloro para la Docencia e Investigación Médica Ciudad Autonoma de Buenos Aires
Australia Monash Medical Centre Clayton Clayton
Australia Peter MacCallum Cancer Centre Melbourne
Australia The Alfred Hospital Prahran
Belgium UZA Edegem
Belgium UZ Leuven Leuven
Belgium AZ Delta Menen
Brazil Fundação Doutor Amaral Carvalho Jaú
Brazil Liga Norte-Rio-Grandense Contra o Câncer Natal Rio Grande Do Norte
Brazil Instituto Nacional de Câncer José Alencar Gomes da Silva Rio De Janeiro
Brazil CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia Santo André
Brazil Fundação Faculdade Regional de Medicina de São José do Rio Preto São José Do Rio Preto
Chile CeCim Biocinetic Santiago Region Met
Chile Centro de Estudios Clínicos SAGA Santiago
Chile Instituto Clinico Oncologico Temuco
France Institut Sainte Catherine Avignon
France CHU Besançon - Hôpital Jean Minjoz Besancon
France Centre Georges François Leclerc Dijon
France Hôpital Saint-Antoine Paris
France Hôpital Saint-Louis Paris
France Institut Gustave Roussy Villejuif
Germany Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt Dresden
Germany Universitaetsklinikum Carl Gustav Carus TU Dresden Dresden Sachsen
Germany Krankenhaus Nordwest GmbH Frankfurt
Germany Medizinische Hochschule Hannover Hannover Niedersachsen
Germany Uniklinik Mainz Mainz
Germany Universitaetsklinikum Ulm Ulm Baden Wuerttemberg
Italy Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi Bologna
Italy Azienda Ospedaliero Universitaria Mater Domini Catanzaro
Italy Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda) Milano
Italy Fondazione IRCCS Istituto Nazionale dei Tumori Milano
Italy IEO Istituto Europeo di Oncologia Milano
Italy IOV - Istituto Oncologico Veneto IRCCS Padova
Italy Istituto Clinico Humanitas Rozzano
Italy A.O.U. Senese Policlinico Santa Maria alle Scotte Siena
Korea, Republic of National Cancer Center Goyang-si
Korea, Republic of Chonnam National University Hwasun Hospital Hwasun
Korea, Republic of Seoul National University Bundang Hospital Seongnam
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Samsung Medical Center Seoul
Korea, Republic of Seoul National University Hospital Seoul
Korea, Republic of The Catholic University of Korea, Seoul St. Mary's Hospital Seoul
Korea, Republic of Ajou University Hospital Suwon
Poland Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna Lódz
Poland Examen sp. z o.o. Skórzewo
Poland Centrum Zdrowia MDM Warszawa
Poland Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy Warszawa
Russian Federation SAIH "Republican Clinical Oncological Dispensary of the Ministry of Healthcare of Republic Tatarstan Kazan
Russian Federation "VitaMed" LLC Moscow
Russian Federation FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin" Moscow
Russian Federation BHI of Omsk region "Clinical Oncology Dispensary" Omsk
Russian Federation FSBI "Clinical Research and Practical Center for specialized medical care (oncology)" Pesochnyy
Russian Federation FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov" Saint Petersburg
Russian Federation Pavlov First Saint Petersburg State Medical University Saint Petersburg
Russian Federation Tomsk Research Instutite of Oncology Tomsk
Russian Federation SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan Ufa
Spain Hospital Clinic de Barcelona Barcelona
Spain Hospital del Mar Barcelona
Spain Hospital Universitari Vall d'Hebron Barcelona
Spain ICO l'Hospitalet - Hospital Duran i Reynals L'Hospitalet de Llobregat
Spain Centro Integral Oncologico Clara Campal Madrid
Spain Hospital Universitario Ramon y Cajal Madrid
Spain MD Anderson Cancer Centre Madrid
Spain Clinica Universidad de Navarra Pamplona
Turkey Baskent University Adana Application and Research Center Adana
Turkey Ankara City Hospital Ankara
Turkey Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital Ankara
Turkey Hacettepe University Medical Faculty Ankara
Turkey Akdeniz University Medical Faculty Antalya
Turkey Istanbul Medeniyet Uni Goztepe Training&Res Hosp Istanbul
Turkey Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty Istanbul
Turkey Kocaeli Universitesi Tip Fakultesi Kocaeli
United Kingdom Addenbrooke's Hospital Cambridge
United Kingdom Ninewells Hospital Dundee
United Kingdom Beatson West of Scotland Cancer Centre Glasgow
United Kingdom University College London Hospitals London
United Kingdom The Christie Manchester
United Kingdom Royal Marsden Hospital- Sutton Sutton
United States Memorial Sloan Kettering Cancer Center New York New York
United States AdventHealth Cancer Institute Orlando Florida

Sponsors (1)

Lead Sponsor Collaborator
Basilea Pharmaceutica

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Chile,  France,  Germany,  Italy,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  Turkey,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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.
From first dose and up to 18 months
Primary 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 From first dose and up to 4 months
Primary 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. From first dose and up to 18 months
Secondary 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. From first dose and up to 9 months
Secondary 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. From first dose and up to 18 months
Secondary 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 From first dose and up to 9 months
Secondary Overall Survival (OS) in Substudy 1 in Cohort 1.3 OS was measured from patient enrollment to time of death. From first dose and up to 9 months
Secondary OS in Substudy 2 OS was measured from patient enrollment to time of death From first dose and up to 15 months
Secondary ORR in Substudy 2 ORR was defined by the percentage of patients with CR or PR by BICR per RECIST version 1.1. From first dose and up to 15 months
Secondary DCR in Substudy 2 Defined as the percentage of patients with confirmed CR, PR or SD by BICR per RECIST version 1.1. From first dose and up to 15 months
Secondary 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). From first dose and up to 15 months
Secondary PFS in Substudy 2 PFS was calculated from patient enrollment to progressive disease (PD) date by BICR per RECIST version 1.1. From first dose and up to 15 months
Secondary 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. 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
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