EUCROSS: European Trial on Crizotinib in ROS1 Translocated Lung Cancer

NCT02183870 | Completed Phase 2 DMC

• 3 other identifiers: EUCROSS2013-002737-38DRKS00005409
• Study Type: interventional
• Target: 34
• Locations: 3 countries
• Sites: 18

Brief Summary

EUCROSS is a phase II trial to evaluate the efficacy and safety of crizotinib in patients with adenocarcinoma of the lung harbouring ROS1 translocations. Patients will be treated with 250mg crizotinib bid until progression or intolerable toxicity.

Conditions

Lung Cancer; Adenocarcinoma; NSCLC

Keywords

lung cancer; adenocarcinoma; NSCLC; ROS1; ROS1 translocation; crizotinib; phase II

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR); evaluation criteria: investigator assessed RECIST v.1.1 analysis

  CT/MRI scans will be performed to evaluate the efficacy of crizotinib treatment in advanced adenocarcinoma of the lung harbouring ROS1 fusion genes (primary outcome measure: objective response rate (ORR) according to RECIST v.1.1)

  From time of beginning of treatment until the documention of response according to RECIST v1.1 (expected average 12 months) .

Secondary Outcomes (9)

• Progression Free Survival (PFS) according to RECIST v1.1; evaluation criteria: investigator assessed RECIST v.1.1 analysis

  From time of beginning of treatment until the first documented event of progression according to RECIST v1.1 (expected average 12 months).

• Overall Survival (OS); evaluation criteria: investigator assessed RECIST v.1.1 analysis

  From beginning to end of study (Last subject last visit (LSLV)) (up to approximately 24 months).

• Duration of Response (DR); evaluation criteria: investigator assessed RECIST v.1.1 analysis

  From time of beginning of treatment until the documention of progression according to RECIST v1.1 (expected average 12 months).

• Time to Tumor Response; evaluation criteria: investigator assessed RECIST v.1.1 analysis

  From time of beginning of treatment until the first documented event of response according to RECIST v1.1 (expected average 3 months).

• Disease Control Rate (DCR); evaluation criteria: investigator assessed RECIST v.1.1 analysis

  From beginning of treatment to week 6, 12 and 24 according to RECIST v1.1 (expected average 3 months).

Other Outcomes (2)

• Characterization of ROS1 fusion gene on a genomic level by CAGE Technology to identify the exact break-apart point as well as the involved fusion genes.

  From beginning of screening of first patient to screening of last patient (expected average 24 months).

• Characterization of molecular and genetic mechanisms of resistance to crizotinib treatment in patients showing disease progression.

  At time of disease progression (expected average 12 months).

Study Arms (1)

Crizotinib

EXPERIMENTAL

Patients are treated in this single-arm trial with oral crizotinib 250 mg b.i.d.. Treatment dose will be adjusted according to the protocol if indicated. Treatment will be conducted until disease progression or beyond disease progression according to the protocol if clinically indicated.

Drug: Crizotinib

Interventions

Crizotinib DRUG

250mg crizotinib bid until end of treatment

Also known as: Xalkori

Crizotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with adenocarcinoma of the lung that is locally advanced or metastatic independent from the number of prior lines of therapy, i.e. including non-pretreated patients (UICC stage IIIB or IV)
• Positive for ROS1 translocation by central FISH-testing
• Ability to swallow pills
• Age \> 18 years
• ECOG performance status 0 to 2
• Life expectancy of at least 12 weeks
• Disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1)
• Any prior treatment (chemotherapy, radiation or surgery) must have been completed at least 2 weeks prior to initiation of study medication
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 14 days prior to screening:
• Hemoglobin ≥ 8.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1,000 /mm3
• Platelet count ≥ 50 000/µL
• Total bilirubin ≤ 2 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AP) ≤ 2,5 x ULN or ≤ 5 x ULN in case of liver involvement
• PT-INR/PTT ≤ 1.5 x ULN

You may not qualify if:

• Previous treatment with specific ALK or ROS1 inhibitors
• Current treatment within another therapeutic clinical trial
• Other history of ongoing malignancy that would potentially interfere with the interpretation of efficacy (early stage or chronic disease is allowed if not requiring active therapy or intervention and being under control)
• Pregnancy or breastfeeding
• Use of drugs or foods that are known potent CYP3A4 inhibitors, including but not limited to atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole and grapefruit or grapefruit juice
• Use of drugs that are known potent CYP3A4 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort
• Use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited to dihydroergotamine, ergotamine, pimozide, astemizole, cisapride, and terfenadine
• Active CNS metastases. Patients with brain metastasis are eligible if asymptomatic for ≥ 14 days before starting study medication and off corticosteroids.
• History of or known carcinomatous meningitis or leptomeningeal disease
• Known diagnosis of HIV, active hepatitis B and/or C (testing is not mandatory)
• Any person being in an institution on assignment of the respective authority against his/her own will
• Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information
• Ongoing cardiac dysrhythmias of CTCAE grade ≥2, uncontrolled atrial fibrillation of any grade or QTcF interval \> 470ms
• Patients with known interstitial fibrosis or interstitial lung disease
• Any of the following within 3 months prior to first crizotinib administration:

Sponsors & Collaborators

• University of Cologne: lead
• Spanish Lung Cancer Group: collaborator
• Pfizer: collaborator

Study Sites (18)

Thoraxklinik Heidelberg

Heidelberg, Baden-Würtemberg, 69126, Germany

Location

Universitätsklinikum Frankfurt - Medizinische Klinik II

Frankfurt a.M., Hesse, 60590, Germany

Location

LungenClinic Großhansdorf

Großhansdorf, Schleswig-Holstein, 22927, Germany

Location

Evangelische Lungenklinik Berlin

Berlin, 13125, Germany

Location

University of Cologne / LCGC

Cologne, 50937, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

Maria Rosaria Garcia Campelo

A Coruña, Spain

Location

CEIC Hospital General Universitario de Alicante

Alicante, Spain

Location

CEIC Hopsital Vall d'Hebron

Barcelona, Spain

Location

Institut Catala D'Oncologia

Barcelona, Spain

Location

Hospital Universitario Materno-Infantil de Canarias

Las Palmas de Gran Canaria, Spain

Location

CEIC Área 2 - Hospital Universitario de La Princesa

Madrid, Spain

Location

CEIC Área 6 - Hospital Universitario Puerta de Hierro de Majadahonda

Majadahonda, Spain

Location

CEIC Malaga Nordeste - Hospital Regional Universitario Carlos Haya

Málaga, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, Spain

Location

CEIC Hospital Universitario Virgen del Rocio

Seville, Spain

Location

CEIC Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Universitätsspital Basel

Basel, Switzerland

Location

Related Publications (2)

• Bos M, Gardizi M, Schildhaus HU, Heukamp LC, Geist T, Kaminsky B, Zander T, Nogova L, Scheffler M, Dietlein M, Kobe C, Holstein A, Maintz D, Buttner R, Wolf J. Complete metabolic response in a patient with repeatedly relapsed non-small cell lung cancer harboring ROS1 gene rearrangement after treatment with crizotinib. Lung Cancer. 2013 Jul;81(1):142-3. doi: 10.1016/j.lungcan.2013.02.018. Epub 2013 Apr 1.

  PMID: 23558310 BACKGROUND

• Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, Asaka R, Hamanaka W, Ninomiya H, Uehara H, Lim Choi Y, Satoh Y, Okumura S, Nakagawa K, Mano H, Ishikawa Y. RET, ROS1 and ALK fusions in lung cancer. Nat Med. 2012 Feb 12;18(3):378-81. doi: 10.1038/nm.2658.

  PMID: 22327623 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms; Adenocarcinoma

Interventions

Crizotinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Study Officials

• Juergen Wolf, Prof. Dr. med.

  Uniklinik Köln, Department I for Internal Medicine, LCGC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dr. med., Leader of the LCGC

Study Record Dates

• First Submitted: June 25, 2014
• First Posted: July 8, 2014
• Study Start: May 1, 2014
• Primary Completion: July 24, 2018
• Study Completion: February 29, 2020
• Last Updated: June 16, 2022

Record last verified: 2022-06

Locations

CH (1); DE (6); ES (11)