EUCROSS: European Trial on Crizotinib in ROS1 Translocated Lung Cancer

NCT ID: NCT02183870

Last Updated: 2022-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2020-02-29

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.

Detailed Description

EUCROSS is a phase II trial to evaluate the efficacy and safety of crizotinib in patients with adenocarcinoma of the lung harbouring ROS1 translocations. In individual treatment attempts and an ongoing phase I trial crizotinib has shown remarkable effects on this selected subgroup of lung cancer patients. Crizotinib is a tyrosine kinase inhibitor, blocking the catalytic activity of rearranged ALK and ROS1 as well as MET. The patients eligible for the trial will be treated with 250mg crizotinib twice-daily. Tumor response to treatment will be assessed every 6 weeks by CT or MRI scans. In case of progression treatment beyond may be conducted if clinically indicated. To identify mechanisms of resistance to crizotinib treatment, an optional re-biopsy may be performed in these cases and fresh frozen tumor material will analyzed at the University of Cologne.

Conditions

Lung Cancer; Adenocarcinoma; NSCLC

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Crizotinib

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.

Group Type: EXPERIMENTAL

Crizotinib

Intervention Type: DRUG

250mg crizotinib bid until end of treatment

Interventions

Crizotinib

250mg crizotinib bid until end of treatment

Intervention Type: DRUG

Other Intervention Names

Xalkori

Eligibility Criteria

Inclusion Criteria

• 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
• Serum creatinine ≤ 2 times ULN
• Calculated creatinine clearance (CLcr) ≥ 40 ml/min (Cockcroft-Gault formula)
• Written informed consent
• Negative serum pregnancy test within 3 days prior to start of dosing premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for ≥ 1 year.

Fertile men and women must have an effective method of contraception during treatment and for at least 3 months after completion of treatment as directed by their physician. Effective methods of contraception result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the investigator, acceptable methods of contraception may include total abstinence where lifestyle of the patient ensures compliance (Periodic abstinence and withdrawal are not acceptable methods of contraception).

Exclusion Criteria

• 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:

Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack

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

Sponsors

Spanish Lung Cancer Group

OTHER

Sponsor Role: collaborator

Pfizer

INDUSTRY

Sponsor Role: collaborator

University of Cologne

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Juergen Wolf

Professor Dr. med., Leader of the LCGC

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Juergen Wolf, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Uniklinik Köln, Department I for Internal Medicine, LCGC

Locations

Thoraxklinik Heidelberg

Heidelberg, Baden-Würtemberg, Germany

Universitätsklinikum Frankfurt - Medizinische Klinik II

Frankfurt a.M., Hesse, Germany

LungenClinic Großhansdorf

Großhansdorf, Schleswig-Holstein, Germany

Evangelische Lungenklinik Berlin

Berlin, , Germany

University of Cologne / LCGC

Cologne, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

Maria Rosaria Garcia Campelo

A Coruña, , Spain

CEIC Hospital General Universitario de Alicante

Alicante, , Spain

CEIC Hopsital Vall d'Hebron

Barcelona, , Spain

Institut Catala D'Oncologia

Barcelona, , Spain

Hospital Universitario Materno-Infantil de Canarias

Las Palmas de Gran Canaria, , Spain

CEIC Área 2 - Hospital Universitario de La Princesa

Madrid, , Spain

CEIC Área 6 - Hospital Universitario Puerta de Hierro de Majadahonda

Majadahonda, , Spain

CEIC Malaga Nordeste - Hospital Regional Universitario Carlos Haya

Málaga, , Spain

Hospital Son Llatzer

Palma de Mallorca, , Spain

CEIC Hospital Universitario Virgen del Rocio

Seville, , Spain

CEIC Hospital Clínico Universitario de Valencia

Valencia, , Spain

Universitätsspital Basel

Basel, , Switzerland

Countries

Germany; Spain; Switzerland

References

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.

Reference Type: BACKGROUND

PMID: 23558310 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22327623 (View on PubMed)

Other Identifiers

2013-002737-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DRKS00005409

Identifier Type: OTHER

Identifier Source: secondary_id

EUCROSS

Identifier Type: -

Identifier Source: org_study_id