Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma

NCT ID: NCT04604132

Last Updated: 2024-04-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-06
• Study Completion Date: 2022-11-21

Brief 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).

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Derazantinib

Intervention Type: DRUG

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

Substudy 1: Cohort 1.2 Derazantinib 300 mg once daily

Patients with FGFR1-3 mutations were treated with 300 mg Derazantinib monotherapy once daily

Group Type: EXPERIMENTAL

Derazantinib

Intervention Type: DRUG

Derazantinib was administered orally at a dose of 300 mg once daily as monotherapy in the Substudy 1 (Cohort 1.2).

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

Group Type: EXPERIMENTAL

Derazantinib

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Derazantinib-paclitaxel-ramucirumab combination

Intervention Type: DRUG

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.

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

Group Type: EXPERIMENTAL

Derazantinib-paclitaxel-ramucirumab combination

Intervention Type: DRUG

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.

Interventions

Derazantinib

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

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Derazantinib

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

Intervention Type: DRUG

Derazantinib

Derazantinib was administered orally at a dose of 300 mg once daily as monotherapy in the Substudy 1 (Cohort 1.2).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

• 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 Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Basilea Pharmaceutica

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Manuel Häckl, MD

Role: STUDY_DIRECTOR

Basilea Pharmaceutica International Ltd, Allschwil

Locations

AdventHealth Cancer Institute

Orlando, Florida, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Fundación Favaloro para la Docencia e Investigación Médica

Buenos Aires, , Argentina

Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo

Ciudad Autonoma Buenos Aires, , Argentina

Monash Medical Centre Clayton

Clayton, , Australia

Peter MacCallum Cancer Centre

Melbourne, , Australia

The Alfred Hospital

Prahran, , Australia

UZA

Edegem, , Belgium

UZ Leuven

Leuven, , Belgium

AZ Delta

Menen, , Belgium

Liga Norte-Rio-Grandense Contra o Câncer

Natal, Rio Grande do Norte, Brazil

Fundação Doutor Amaral Carvalho

Jaú, , 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, , Brazil

CeCim Biocinetic

Santiago, Region Met, Chile

Centro de Estudios Clínicos SAGA

Santiago, , Chile

Instituto Clinico Oncologico

Temuco, , Chile

Institut Sainte Catherine

Avignon, , France

CHU Besançon - Hôpital Jean Minjoz

Besançon, , France

Centre Georges François Leclerc

Dijon, , France

Hôpital Saint-Louis

Paris, , France

Hôpital Saint-Antoine

Paris, , France

Institut Gustave Roussy

Villejuif, , France

Universitaetsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Saxony, Germany

Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt

Dresden, , Germany

Krankenhaus Nordwest GmbH

Frankfurt, , Germany

Uniklinik Mainz

Mainz, , Germany

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

Bologna, , Italy

Azienda Ospedaliero Universitaria Mater Domini

Catanzaro, , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

IEO Istituto Europeo di Oncologia

Milan, , Italy

Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)

Milan, , Italy

IOV - Istituto Oncologico Veneto IRCCS

Padua, , Italy

Istituto Clinico Humanitas

Rozzano, , Italy

A.O.U. Senese Policlinico Santa Maria alle Scotte

Siena, , Italy

Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna

Lodz, , Poland

Examen sp. z o.o.

Skórzewo, , Poland

Centrum Zdrowia MDM

Warsaw, , Poland

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

Warsaw, , Poland

SAIH "Republican Clinical Oncological Dispensary of the Ministry of Healthcare of Republic Tatarstan

Kazan', , Russia

FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"

Moscow, , Russia

"VitaMed" LLC

Moscow, , Russia

BHI of Omsk region "Clinical Oncology Dispensary"

Omsk, , Russia

FSBI "Clinical Research and Practical Center for specialized medical care (oncology)"

Pesochnyy, , Russia

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, , Russia

FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"

Saint Petersburg, , Russia

Tomsk Research Instutite of Oncology

Tomsk, , Russia

SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan

Ufa, , Russia

National Cancer Center

Goyang-si, , South Korea

Chonnam National University Hwasun Hospital

Hwasun, , South Korea

Seoul National University Bundang Hospital

Seongnam, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

Ajou University Hospital

Suwon, , South Korea

Hospital del Mar

Barcelona, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

ICO l'Hospitalet - Hospital Duran i Reynals

L'Hospitalet de Llobregat, , Spain

MD Anderson Cancer Centre

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Centro Integral Oncologico Clara Campal

Madrid, , Spain

Clinica Universidad de Navarra

Pamplona, , Spain

Baskent University Adana Application and Research Center

Adana, , Turkey (Türkiye)

Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital

Ankara, , Turkey (Türkiye)

Ankara City Hospital

Ankara, , Turkey (Türkiye)

Akdeniz University Medical Faculty

Antalya, , Turkey (Türkiye)

Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Istanbul Medeniyet Uni Goztepe Training&Res Hosp

Istanbul, , Turkey (Türkiye)

Kocaeli Universitesi Tip Fakultesi

Kocaeli, , Turkey (Türkiye)

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 Kingdom

Countries

United States; Argentina; Australia; Belgium; Brazil; Chile; France; Germany; Italy; Poland; Russia; South Korea; Spain; Turkey (Türkiye); United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

DZB-CS-202

Identifier Type: -

Identifier Source: org_study_id