Cross-tumoral Phase 2 clinical trial exploring Crizotinib (PF-02341066) in patients with advanced tumours induced by causal alterations of either ALK or MET.

Phase 2

Completed

• Conditions: Anaplastic large cell lymphoma; Inflammatory myofibroblastic tumor; Papillary renal cell carcinoma type 1; Alveolar soft part sarcoma; Clear cell sarcoma; Alveolar rhabdomyosarcoma; 10018849; 10027656

• Registration Number: NL-OMON55860
• Lead Sponsor: European Organisation for Research in Treatment of Cancer (EORTC)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 24

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, paraffinembedded,
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 years, 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. (Appendix F).
* 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. AST and ALT <= 2.5 x ULN
in the absence of liver metastases and metastases <= 5 x UNL if liver function
abnormalities are due to the underlying malignancy.
* Note: Crizotinib should be avoided in patients with congenital long QT
syndrome
* Machine-read ECG with QTcF interval <470 msec.
* Able to swallow capsules.
* 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

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 and no cerebrovascular accident including
transient ischemic attack.
* Current congestive heart failure.
* 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 wi

Study & Design

• Study Type: Interventional
• Study Design: Not specified