E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced and/or metastatic malignant tumor (anaplastic large cell lymphoma, inflammatory myofibroblastic tumor, papillary renal cell carcinoma type 1, alveolar soft part sarcoma, clear cell sarcoma or alveolar rhabdomyosarcoma) deemed incurable by conventional surgery, radiotherapy, systemic therapy or any other means. |
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E.1.1.1 | Medical condition in easily understood language |
Local diagnosis of locally advanced and/or metastatic sub types of lymphoma, RCC and soft tissue sarcoma deemed incurable by surgery, radiotherapy, systemic therapy or any other means. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065867 |
E.1.2 | Term | Alveolar rhabdomyosarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067918 |
E.1.2 | Term | Inflammatory myofibroblastic tumor |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002227 |
E.1.2 | Term | Anaplastic large cell lymphoma T- and null-cell types |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001882 |
E.1.2 | Term | Alveolar soft part sarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067946 |
E.1.2 | Term | Renal cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065865 |
E.1.2 | Term | Clear cell sarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The study will primarily assess the efficacy 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. |
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E.2.2 | Secondary objectives of the trial |
To study the specificity of the kinase inhibitor for tumors in all cohorts by explorative comparison of treatment results in patients with the same disease type with and without genetic alterations in ALK and/or MET. To investigate sensitive and reliable methodologies for patient screening for such defects, to be potentially cross-validated and further developed by an accredited laboratory in later steps, based on prospectively collected biological material from this trial. To explore the potential value of selected biomarkers to study the pharmacological effects of crizotinib. To explore whether molecularly driven, high quality multi-tumor screening Phase II trials are feasible in a multiinstitutional, multidisciplinary setting, when screening and treatment are performed by EORTC (+:- additional selected sites). To study soluble serum factors leading to MET pathway activation as predictive biomarkers for response to treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Step 1 registration: • Local diagnosis of locally advanced and/or metastatic malignant tumor (defined before) deemed incurable by conventional surgery, radiotherapy, systemic therapy or any other means. • Mandatory shipment of tumor-containing tissue blocks. Step 2 registration: • Measurable disease according to RECIST 1.1 with target lesion of at least 20 mm (or 10 mm on spiral CT scans). • Minimum age 15 years, no upper age limit. • Eastern Cooperative Oncology Group (ECOG) performance status 0-2. • Adequate hematological function: ANC ≥ 1 x 109/L, platelets ≥ 30 x 109/L and hemoglobin ≥ 8 g/dl. • Adequate renal function: serum creatinine ≤ 2 x ULN. • Adequate liver function: Bilirubin ≤ 1.5 x ULN. AST and ALT ≤ 2.5 x ULN in the absence of liver metastases and ≤ 5 x UNL if liver function abnormalities are due to the underlying malignancy. • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. • Negative pregnancy test • All patients (male and female) of childbearing/reproductive potential must use adequate birth control measures during the study treatment period and for at least three months after the last study treatment • Written consent before registration Additional inclusion criteria linked to specific tumor type are described in the protocol in section 3.2. |
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E.4 | Principal exclusion criteria |
Step 2 registration: • Carcinomatous meningitis or leptomeningeal disease. • 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). • Prior therapy directly targeting ALK and/or MET, previous treatment with crizotinib. • Previous and active malignancy for the last three years with the exception of non-melanoma skin cancer, localized cervical cancer, localized and presumably cured prostate cancer or adequately treated basal or squamous cell skin carcinoma. • Acute or chronic severe gastrointestinal conditions such as diarrhea or ulcer. • Current congestive heart failure. • Ongoing cardiac dysrhythmias of NCI CTCAE Grade >2. • Uncontrolled atrial fibrillation of any grade. • Pregnant women |
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E.5 End points |
E.5.1 | Primary end point(s) |
Response rate documented by RECIST 1.1 (with response confirmation). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of trial (per cohort). |
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E.5.2 | Secondary end point(s) |
Safety (CTAE v 4.0) Progression free survival Clinical benefit, as assessed by the rate of CR+PR+ Stable Disease (SD) Overall survival Duration of clinical benefit |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the end of trial (per cohort). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study occurs when all of the following criteria have been satisfied: 1. Thirty days after all patients have stopped protocol treatment 2. The trial is mature for the analysis of the primary endpoint as defined in the protocol, if the trial reaches its primary endpoint 3. The database has been fully cleaned and frozen for this analysis |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |