A phase 1B of crizotinib either in combination or as single agent in pediatric patients with ALK, ROS1 or MET positive malignancies;Study ITCC 053
- Conditions
- cancermalignancies10027655
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 20
Inclusion criteria
1b en 2:Histologically or cytologically confirmed diagnosis of
relapsed/refractory ALCL, including first relapse, NBL or RMS
3: Histologically confirmed diagnosis of other solid tumor or lymphomas other
than ALCL that is relapsed or refractory to standard therapy, or patients with
newly diagnosed IMT for whom surgery may not be feasible for close proximity to
vital structures, without prior tumor-shrinkage and no other feasible options
are available as per local standard of care.when stratum 1b is completed, ALCL
patients will be eligible to enroll into stratum 3
• Age at enrolment >=1 year of age and <= 21 years
• Lansky play score > 60%; or Karnofsky performance status > 60%.
Target gene aberration as defined as:
o stratum 1b: The t(2;5) translocation or rearrangement t(1;2), t(2;3), inv(2),
t(2;22). proven by ALK- immunohistochemistry, FISH or NGS
stratum 2: A point mutation in the kinase domain of ALK, An amplification of
the ALK gene,rearrangement in >15% of the tumor cells or An amplification of
the MET-gene,MET mutation, TFE3 rearrangement,
stratum 3:
o A point mutation in the kinase domain of ALK, or MET mutation
o An amplification of the ALK or MET gene,
o A ROS1 or TFE3 rearrangement in > 15% of the tumor cells
• Life expectancy >= 12 weeks
• Disease involvement :
o stratum 1b Measurable disease defined as at least one nodule with a longest
diameter greater than 1.5 cm (pediatric NHL response criteria)
stratum 2: For dose escalation measurable and non-measurable disease is
allowed; For dose expansion measurable disease is mandated, except for
neuroblastomas where MIBG or FDG avidity is sufficient
stratum 3:Measurable disease according to RECIST 1.1
Or, measurable disease as defined as at least one nodule with a longest
diameter greater than 1.5 cm
• Any previous systemic anticancer therapy must have been completed at least 2
weeks prior to initiation of study medication
• No prior therapy directly targeting ALK or ROS1 or MET
• No treatment with any other investigational drug within the past 2 weeks or
major surgery
Male and female patients of child-bearing potential must agree to use an
effective method for males and a highly effective method for females
• Other serious illnesses or medical conditions, • Current uncontrolled
infection, • History of allergic reactions to the compounds or their solvents,
• Patients with untreated CNS metastases and/or primary CNS tumors and/or
meningeal, lymphoma involvement, defined as CNS3 status (patients with CNS2 are
eligible), • Concurrent use of drugs or foods that are known potent CYP3A4
inducers or inhibitors CYP3A4 substrates with narrow therapeutic indices as
well as medication with known QT*prolongation, •• Any of the following within
the 3 months prior to starting study treatment: myocardial infarction,
severe/unstable angina, coronary/peripheral artery bypass graft, congestive
heart failure or cerebrovascular accident including transient ischemic attack.
• Use of live vaccines within 30 days of first dosing
* Impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the, absorption of crizotinib (e.g., ulcerative diseases,
uncontrolled nausea, vomiting, diarrhea,, or malabsorption syndrome), • Not
able to comply with scheduled follow*up and with management of toxicity., • A
cardiac shortening fraction < 29%, • Ongoing cardiac dysrhythmias of NCI
CTCAE Grade >=2, uncontrolled atrial fibrillation of any, grade, or QTcF
interval >470 msec., • 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., • No
evidence of active graft*vs*host disease (GVHD) and at least 3 months post*
allogeneic, HSCT. Must not receive GVHD prophylaxis., • For patients with
childbearing potential, a negative test for pregnancy and agreement to use,
effective contraceptive measures is required before entry on study.,• Spinal
cord compression unless treated with the patient attaining good pain control
and stable or recovered neurologic function.
• Prior malignancy (other than current malignancy): patients will not be
eligible if they have evidence of active malignancy (other than non-melanoma
skin cancer or localized cervical cancer, or localized and presumed cured
prostate cancer) within the last 3 years.
• Carcinomatous meningitis or leptomeningeal disease
Plus for stratum 2:, • Patients with neuroblastoma and bone marrow disease
only, are excluded.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Dose Limiting Toxicities (DLT) during the first cycle of crizotinib, in<br /><br>combination with temsirolimus. For stratum 2; overall response rate for<br /><br>stratum 1b and 3.</p><br>
- Secondary Outcome Measures
Name Time Method