CREATE: Cross-tumoral Phase 2 With Crizotinib

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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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

Intervention / Treatment
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* Drug: Crizotinib (PF-02341066)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crizotinib in Anaplastic large cell lymphoma<br> | Drug: Crizotinib (PF-02341066)<br>* 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.<br>|
| Experimental: Crizotinib in Inflammatory myofibroblastic tumor<br> | Drug: Crizotinib (PF-02341066)<br>* 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.<br>|
| Experimental: Crizotinib in Papillary renal cell carcinoma type 1<br> | Drug: Crizotinib (PF-02341066)<br>* 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.<br>|
| Experimental: Crizotinib in Clear cell sarcoma<br> | Drug: Crizotinib (PF-02341066)<br>* 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.<br>|
| Experimental: Crizotinib in Alveolar soft part sarcoma<br> | Drug: Crizotinib (PF-02341066)<br>* 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.<br>|
| Experimental: Crizotinib in Alveolar rhabdomyosarcoma<br> | Drug: Crizotinib (PF-02341066)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (reporting of adverse events according to CTCAE v4.0) |  |  | 
| Progression free survival |  |  | 
| Disease control rate |  |  | 
| Overall survival |  |  | 
| Duration of response |  |  | 
| Correlative research endpoints |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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