CREATE: Cross-tumoral Phase 2 With Crizotinib

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01524926

Collaborator

Pfizer (Industry)

582

Enrollment

Locations

Arms

135

Anticipated Duration (Months)

23.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Crizotinib (PF-02341066)	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

582 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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")

Actual Study Start Date :

Sep 1, 2012

Actual Primary Completion Date :

Dec 6, 2017

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Crizotinib in Anaplastic large cell lymphoma	Drug: Crizotinib (PF-02341066) For patients of 15yo and older, Capsules of 200 and 250 mg Daily dose of 500, 400 or 250 mg/day depending on toxicitie; for patients younger than 15yo, 280 mg/m²/dose BID, with reductions allowed to 80% as first reduction and to 60% as second reduction respectively of the initial dose.
Experimental: Crizotinib in Inflammatory myofibroblastic tumor	Drug: Crizotinib (PF-02341066) For patients of 15yo and older, Capsules of 200 and 250 mg Daily dose of 500, 400 or 250 mg/day depending on toxicitie; for patients younger than 15yo, 280 mg/m²/dose BID, with reductions allowed to 80% as first reduction and to 60% as second reduction respectively of the initial dose.
Experimental: Crizotinib in Papillary renal cell carcinoma type 1	Drug: Crizotinib (PF-02341066) For patients of 15yo and older, Capsules of 200 and 250 mg Daily dose of 500, 400 or 250 mg/day depending on toxicitie; for patients younger than 15yo, 280 mg/m²/dose BID, with reductions allowed to 80% as first reduction and to 60% as second reduction respectively of the initial dose.
Experimental: Crizotinib in Clear cell sarcoma	Drug: Crizotinib (PF-02341066) For patients of 15yo and older, Capsules of 200 and 250 mg Daily dose of 500, 400 or 250 mg/day depending on toxicitie; for patients younger than 15yo, 280 mg/m²/dose BID, with reductions allowed to 80% as first reduction and to 60% as second reduction respectively of the initial dose.
Experimental: Crizotinib in Alveolar soft part sarcoma	Drug: Crizotinib (PF-02341066) For patients of 15yo and older, Capsules of 200 and 250 mg Daily dose of 500, 400 or 250 mg/day depending on toxicitie; for patients younger than 15yo, 280 mg/m²/dose BID, with reductions allowed to 80% as first reduction and to 60% as second reduction respectively of the initial dose.
Experimental: Crizotinib in Alveolar rhabdomyosarcoma	Drug: Crizotinib (PF-02341066) For patients of 15yo and older, Capsules of 200 and 250 mg Daily dose of 500, 400 or 250 mg/day depending on toxicitie; for patients younger than 15yo, 280 mg/m²/dose BID, with reductions allowed to 80% as first reduction and to 60% as second reduction respectively of the initial dose.

Outcome Measures

Primary Outcome Measures

Antitumor activity of crizotinib []
To study the antitumor activity of crizotinib across predefined tumor types in patients whose tumors are harboring specific alterations in ALK and/or MET

Secondary Outcome Measures

Safety (reporting of adverse events according to CTCAE v4.0) []
Progression free survival []
Disease control rate []
Overall survival []
Duration of response []
Correlative research endpoints []

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	Hôpitaux Universitaires Bordet-Erasme - Institut Jules Bordet	Brussels	Belgium
2	U.Z. Gasthuisberg	Leuven	Belgium
3	Institut Bergonie	Bordeaux	France
4	Centre Georges-Francois-Leclerc	Dijon	France
5	Centre Leon Berard	Lyon	France
6	Assistance Publique - Hôpitaux de Marseille - Hôpital de La Timone	Marseille	France
7	Institut Gustave Roussy	Villejuif	France
8	Helios Klinikum Bad Saarow	Bad Saarow	Germany
9	Universitaetsklinikum Carl Gustav Carus	Dresden	Germany
10	Universitaetsklinikum - Essen	Essen	Germany
11	Medizinische Hochschule Hannover	Hannover	Germany
12	UniversitaetsMedizin Mannheim	Mannheim	Germany
13	Klinikum Grosshadern Ludwig-Maximilians Univ. Muenchen	Muenchen	Germany
14	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Italy
15	Leiden University Medical Centre	Leiden	Netherlands
16	Radboud University Nijmegen Medical Centre	Nijmegen	Netherlands
17	Erasmus MC - Sophia kindersiekenhuis	Rotterdam	Netherlands
18	Oslo University Hospital - Radiumhospitalet	Oslo	Norway
19	Maria Sklodowska-Curie Memorial Cancer Centre	Warsaw	Poland
20	National Cancer Institute	Bratislava	Slovakia
21	The Institute Of Oncology	Ljubljana	Slovenia
22	St. James's University Hospital	Leeds	United Kingdom
23	University College Hospital	London	United Kingdom
24	Christie NHS Foundation Trust	Manchester	United Kingdom
25	Nottingham University Hospitals NHS Trust - City Hospital	Nottingham	United Kingdom