Phase II clinical trial exploring the activity of crizotinib in patients with advanced solid tumors induced by causal alterations of specific receptors (ALK and MET/HGF receptor tyrosine kinases) expressed by cancer cells

Phase 1

• Conditions: ocally 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.; MedDRA version: 20.0Level: PTClassification code 10065867Term: Alveolar rhabdomyosarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10002227Term: Anaplastic large cell lymphoma T- and null-cell typesSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10067918Term: Inflammatory myofibroblastic tumorSystem Organ Class: 100000072955; MedDRA version: 20.0Level: PTClassification code 10001882Term: Alveolar soft part sarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10067946Term: Renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10065865Term: Clear cell sarcomaSystem Organ Class: 100000143827; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-001988-52-GB
• Lead Sponsor: European Organisation for Research and Treatment of Cancer (EORTC)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-06-08
• Last Update Posted: 9 October 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 582

Inclusion Criteria

Step 1 registration:

? Local diagnosis of locally advanced and/or metastatic malignant
tumor (ALCL, IMFT, PRCC, ASPS, CCSA, ARMS) deemed incurable by
conventional surgery, radiotherapy, systemic therapy or any other
means.
? Mandatory availability for shipment of formalin-fixed, paraffin embedded, tumor-containing, non-returnable tissue blocks from primary tumor and/or metastatic site ( Slides not accepted). Information on previous histopathology reports and previous molecular analysis will be entered in an eCRF, to accompany the tissue samples.
? Written informed consent for central collection of tissue block and any other trial-specific procedures must be obtained from the patient
allowing for collection storage and analysis of tissue and screening
procedures prior to registration.

Step 2 histopathology central confirmation:

? Confirmation of receipt of tissue block and accompanying required
local information, and confirmation that tissue block contains tumor
tissue (quality assurance) by central biorepository through EORTC, as
well as central pathology confirmation, are required before starting the patient screening (step 3) according to chapter 6.4.

Step 3 enrollment:

? Measurable disease according to RECIST 1.1 with target lesion of at
least 20 mm (or 10 mm on spiral CT scans) and presence of at least one RECIST-measurable lesion outside of a previously radiated field or
potential palliative irradiation fields.
? 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.
? Minimum age 1 year, no upper age limit.
? 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 renal function:
A) For patients up to 21 years old:
The Schwartz formula should be used for Clearance Creatinine [mL/min/1.73 m2 = F x Height (cm) x 88.4/creatinine (blood) in µmol/L. ClCr of 80-140 mL/min/1.73 m2 is considered as normal range
- F = 0.55 for boys 1-15 yo
- F = 0.70 for boys 16-21 yo
- F = 0.55 for girls 1-21 yo
B) For patients 21 years or older: serum creatinine = 2 x ULN.
? Adequate liver function: Bilirubin = 1.5 x ULN unless due to Gilbert's syndrome (status of the disease documented by repeated laboratory values with slight increase in bilirubin without any other known causes). 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.
? Clinically normal cardiac function based on the institutional lower limit of normal LVEF (assessed by MUGA or ECHO) and normal 12 lead ECG.
? Machine-read ECG with QTcF interval =470 msec.
? Women of child bearing potential with negative serum pregnancy test
? All patients of childbearing/reproductive potential using adequate
birth control
Disease specific inclusion criteria for patients with anaplastic large cell
lymphoma (ALCL)
? Patient may have received previous systemic treatment, surgery
and/or radiotherapy for localized, locally advanced or advanced disease.
? Patient must have received previous systemic ch

Exclusion Criteria

? Malignant meningitis or leptomeningeal disease.
? Any previous systemic anticancer therapy in the last 4 weeks prior to
initiation of study medication.
? 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.
? Major surgery in past 4 weeks prior to initiation of study medication.
? Prior palliative radiotherapy 24 hrs prior to initiation of study
medication, and minor surgical procedures two weeks prior to the
initiation of study medication.
? Other 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.
? Laboratory abnormalities that would impart, in the judgment of the
investigator and/or sponsor, excess risk associated with study
participation or study drug administration.
? 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.
? Acute or chronic severe gastrointestinal conditions such as diarrhea or ulcer.
? Within the three months prior to starting study treatment, no
myocardial infarction, no severe/unstable angina, no coronary/peripheral artery bypass graft, congestive heart failure or cerebrovascular accident including transient ischemic attack.
? Ongoing cardiac dysrhythmias of NCI CTCAE Grade = 2.
? Uncontrolled atrial fibrillation of any grade.
? History of extensive disseminated/bilateral or known presence of
Grade 3 or 4 interstitial fibrosis or interstitial lung disease, including a
history of pneumonitis, hypersensitivity pneumonitis, interstitial
pneumonia, interstitial lung disease, obliterative bronchiolitis, and
pulmonary fibrosis, but not history of prior radiation pneumonitis.
? Concurrent use of drugs or foods that are known strong CYP3A4
inhibitors, including but not limited to atazanavir, clarithromycin,
indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir,
saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice (refer to section 5.6). The topical use of these medications (if appropriate), such as 2% ketoconazole cream, may be allowed.
? Concurrent use of drugs that are known potent CYP3A4 inducers, within 12 days prior to first dose of crizotinib including but not limited to carbamazepine, phenobarbital, phenytoin,
rifabutin, rifampin, and St. John's wort (refer to section 5.6).
? Use of drugs that are CYP3A4 substrates with narrow therapeutic
indices, including but not limited to pimozide, dihydroergotamine,
ergotamine, astemizole, cisapride, and terfenadine (refer to section 5.6).
? Other severe acute or chronic medical conditions including severe
gastrointestinal conditions such as diarrhea or ulcer) or psychiatric
conditions or end stage renal disease on hemodialysis or laboratory
abnormalities that would impact, in the judgment of the investigator
and/or sponsor, excess risk associated with study participation or study drug administration, and which would, therefore, make the patient inappropriate for study entry.
? Female subjects who are breast feeding
?

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified