Clinical trial NCT01524926: CREATE: Cross-tumoral Phase 2 With Crizotinib
Official title: Cross-tumoral Phase 2 Clinical Trial Exploring Crizotinib (PF-02341066) in Patients With Advanced Tumors Induced by Causal Alterations of ALK and/or MET ("CREATE")
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Locally Advanced and/or Metastatic Anaplastic Large Cell Lymphoma
Locally Advanced and/or Metastatic Inflammatory Myofibroblastic Tumor
Locally Advanced and/or Metastatic Papillary Renal Cell Carcinoma Type 1
Locally Advanced and/or Metastatic Alveolar Soft Part Sarcoma
Locally Advanced and/or Metastatic Clear Cell Sarcoma
Locally Advanced and/or Metastatic Alveolar Rhabdomyosarcoma
Keywords: Phase 2
Crizotinib
Anaplastic large cell lymphoma
Inflammatory myofibroblastic tumor
Papillary renal cell carcinoma type 1
Alveolar soft part sarcoma
Clear cell sarcoma
Alveolar rhabdomyosarcoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: Pfizer
First posted: 2012-02-02
Enrollment: 582
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will primarily assess the antitumor activity of crizotinib in a variety of tumors with alterations in ALK and/or MET pathways. The targeted patient population will include patients with tumors harboring specific alterations leading to ALK and/or MET activation, where tyrosine kinase inhibitors against these targets have not yet been adequately explored.


Eligibility criteria: General inclusion criteria:

* Locally advanced and/or metastatic anaplastic large cell lymphoma
* Locally advanced and/or metastatic inflammatory myofibroblastic tumor
* Locally advanced and/or metastatic papillary renal cell carcinoma type 1
* Locally advanced and/or metastatic alveolar soft part sarcoma
* Locally advanced and/or metastatic clear cell sarcoma
* Locally advanced and/or metastatic alveolar rhabdomyosarcoma.
* The above malignancies must be incurable by conventional surgery, radiotherapy, systemic therapy or any other means.
* Proven presence of specific ALK and/or MET pathway alteration in tumor tissue is not mandatory for patient registration.
* Availability of tumor material for central pathology review
* Written informed consent
* Measurable disease according to RECIST 1.1
* Patients with brain metastases are eligible if treated and/or neurologically stable with no ongoing requirement for corticosteroids (off steroids for at least 2 weeks) and not taking contraindicated medications. Absence of spinal cord compression unless treated with the patient attaining good pain control and stable or recovered neurologic function.
* No carcinomatous meningitis or leptomeningeal disease.
* Any previous systemic anticancer therapy must have been completed at least 4 weeks prior to initiation of study medication.
* No treatment with any other investigational drug within the past 4 weeks or within less than 4 half-life times of the investigational drug before treatment with crizotinib (whatever is the longest period).
* No prior therapy directly targeting ALK and/or MET, no previous treatment with crizotinib.
* Major surgery must have been completed at least 4 weeks prior to initiation of study medication.
* Prior palliative radiotherapy must have been completed at least 24 hrs prior to initiation of study medication, and minor surgical procedures must have been completed at least two weeks prior to the initiation of study medication.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2, or Lansky play scale ≥ 50 for children aged 1 to 12 yo
* Adequate hematological function: ANC ≥ 1 x 109/L, platelets ≥ 30 x 109/L and hemoglobin ≥ 8 g/dL.
* Adequate bone marrow, renal and hepatic functions
* All related adverse events from previous therapies must have recovered to ≤ Grade 1 (except alopecia). No persistence of adverse events from prior anti-cancer therapy deemed clinically relevant.
* No acute or chronic severe gastrointestinal conditions such as diarrhea or ulcerations.
* Normal cardiac function and no cerebrovascular accident including transient ischemic attack.
* No current congestive heart failure.
* No ongoing cardiac dysrhythmias of NCI CTCAE Grade \>2.
* No uncontrolled atrial fibrillation of any grade.
* QTc interval \<470 msec.
* Absence of interstitial lung disease.
* No concurrent use of drugs or foods that are known strongCYP3A4 inhibitors
* No concurrent use of drugs that are known potent CYP3A4 inducers,within 12 days prior to first dose of crizotinib
* No concomitant intercurrent illnesses
* Effective contraception method (if applicable)

Disease-specific inclusion criteria for patients with anaplastic large cell lymphoma

* Patient may have received previous systemic treatment, surgery and/or radiotherapy for localized, locally advanced or advanced disease.
* Patient must have received previous systemic chemotherapy (usually a CHOP-like multidrug combination, if not medically contraindicated, with or without monoclonal antibodies), and may not qualify for further conventional therapy with curative intent.
* No pretreatment limitations (including autologous or allogeneic stem cell- or bone marrow transplantation), provided all other patient selection criteria are met.

Disease-specific inclusion criteria for patients with inflammatory myofibroblastic tumor

* Patient may have received previous systemic treatment, surgery and/or radiotherapy for localized, locally advanced or metastatic disease.
* No mandatory pretreatment.
* No pretreatment limitations, provided all other patient selection criteria are met.

Disease-specific inclusion criteria for patients with papillary renal cell carcinoma type 1

* Patient may have received previous systemic treatment, surgery and/or radiotherapy for localized, locally advanced or metastatic disease.
* No mandatory pretreatment.
* No pretreatment limitations, provided all other patient selection criteria are met.

Disease-specific inclusion criteria for patients with clear cell sarcoma

* Patient may have received previous systemic treatment, surgery and/or radiotherapy for localized, locally advanced or metastatic disease.
* No mandatory pretreatment.
* No pretreatment limitations, provided all other patient selection criteria are met.

Disease-specific inclusion criteria for patients with alveolar soft part sarcoma

* Patient may have received previous systemic treatment, surgery and/or radiotherapy for localized, locally advanced or metastatic disease.
* No mandatory pretreatment.
* No pretreatment limitations, provided all other patient selection criteria are met.

Disease-specific inclusion criteria for patients with alveolar rhabdomyosarcoma

* Patient may have received previous systemic treatment, surgery and/or radiotherapy for localized, locally advanced or metastatic disease.
* Patient must have received previous systemic chemotherapy (usually anthracycline-based, if not medically contraindicated), and may not qualify for further conventional therapy with curative intent.
* No pretreatment limitations, provided all other patient selection criteria are met.

Primary outcomes:
measure: Antitumor activity of crizotinib
Secondary outcomes:
measure: Safety (reporting of adverse events according to CTCAE v4.0)
measure: Progression free survival
measure: Disease control rate
measure: Overall survival
measure: Duration of response
measure: Correlative research endpoints
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Hôpitaux Universitaires Bordet-Erasme - Institut Jules Bordet
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Bordeaux
country: France
facility: Institut Bergonie
city: Dijon
country: France
facility: Centre Georges-Francois-Leclerc
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Assistance Publique - Hôpitaux de Marseille - Hôpital de La Timone
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Bad Saarow
country: Germany
facility: Helios Klinikum Bad Saarow
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus
city: Essen
country: Germany
facility: Universitaetsklinikum - Essen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Mannheim
country: Germany
facility: UniversitaetsMedizin Mannheim
city: Muenchen
country: Germany
facility: Klinikum Grosshadern Ludwig-Maximilians Univ. Muenchen
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
city: Rotterdam
country: Netherlands
facility: Erasmus MC - Sophia kindersiekenhuis
city: Oslo
country: Norway
facility: Oslo University Hospital - Radiumhospitalet
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Centre
city: Bratislava
country: Slovakia
facility: National Cancer Institute
city: Ljubljana
country: Slovenia
facility: The Institute Of Oncology
city: Leeds
country: United Kingdom
facility: St. James's University Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: Manchester
country: United Kingdom
facility: Christie NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust - City Hospital
Study officials:
References:
citation: Schoffski P, Kubickova M, Wozniak A, Blay JY, Strauss SJ, Stacchiotti S, Switaj T, Bucklein V, Leahy MG, Italiano A, Isambert N, Debiec-Rychter M, Sciot R, Lee CJ, Speetjens FM, Nzokirantevye A, Neven A, Kasper B. Long-term efficacy update of crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumour from EORTC trial 90101 CREATE. Eur J Cancer. 2021 Oct;156:12-23. doi: 10.1016/j.ejca.2021.07.016. Epub 2021 Aug 13.
citation: Schoffski P, Sufliarsky J, Gelderblom H, Blay JY, Strauss SJ, Stacchiotti S, Rutkowski P, Lindner LH, Leahy MG, Italiano A, Isambert N, Debiec-Rychter M, Sciot R, Van Cann T, Marreaud S, Nzokirantevye A, Collette S, Wozniak A. Crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumours with and without anaplastic lymphoma kinase gene alterations (European Organisation for Research and Treatment of Cancer 90101 CREATE): a multicentre, single-drug, prospective, non-randomised phase 2 trial. Lancet Respir Med. 2018 Jun;6(6):431-441. doi: 10.1016/S2213-2600(18)30116-4. Epub 2018 Apr 15.
citation: Schoffski P, Wozniak A, Leahy MG, Aamdal S, Rutkowski P, Bauer S, Richter S, Grunwald V, Debiec-Rychter M, Sciot R, Geoerger B, Marreaud S, Collette S, Nzokirantevye A, Strauss SJ. The tyrosine kinase inhibitor crizotinib does not have clinically meaningful activity in heavily pre-treated patients with advanced alveolar rhabdomyosarcoma with FOXO rearrangement: European Organisation for Research and Treatment of Cancer phase 2 trial 90101 'CREATE'. Eur J Cancer. 2018 May;94:156-167. doi: 10.1016/j.ejca.2018.02.011. Epub 2018 Mar 20.
citation: Schoffski P, Wozniak A, Kasper B, Aamdal S, Leahy MG, Rutkowski P, Bauer S, Gelderblom H, Italiano A, Lindner LH, Hennig I, Strauss S, Zakotnik B, Anthoney A, Albiges L, Blay JY, Reichardt P, Sufliarsky J, van der Graaf WTA, Debiec-Rychter M, Sciot R, Van Cann T, Marreaud S, Raveloarivahy T, Collette S, Stacchiotti S. Activity and safety of crizotinib in patients with alveolar soft part sarcoma with rearrangement of TFE3: European Organization for Research and Treatment of Cancer (EORTC) phase II trial 90101 'CREATE'. Ann Oncol. 2018 Mar 1;29(3):758-765. doi: 10.1093/annonc/mdx774.
citation: Schoffski P, Wozniak A, Stacchiotti S, Rutkowski P, Blay JY, Lindner LH, Strauss SJ, Anthoney A, Duffaud F, Richter S, Grunwald V, Leahy MG, Reichardt P, Sufliarsky J, van der Graaf WT, Sciot R, Debiec-Rychter M, van Cann T, Marreaud S, Lia M, Raveloarivahy T, Collette L, Bauer S. Activity and safety of crizotinib in patients with advanced clear-cell sarcoma with MET alterations: European Organization for Research and Treatment of Cancer phase II trial 90101 'CREATE'. Ann Oncol. 2017 Dec 1;28(12):3000-3008. doi: 10.1093/annonc/mdx527.