CREATE: Cross-tumoral Phase 2 With Crizotinib
CREATE: Cross-tumoral Phase 2 With Crizotinib
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.
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.