Phase 2 Study Assessing Efficacy and Safety of Crizotinib in Patients Harboring an Alteration on ALK, MET or ROS1

NCT02034981

Last updated date
Study Location
Gustave Roussy
Villejuif, Ile De France, 94805, France
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Hematologic Cancers, Solid Tumors, Metastatic Cancer
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
1 + year

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Hematologic Cancers, Solid Tumors, Metastatic CancerPhase 2 Study Assessing Efficacy and Safety of Crizotinib in Patients Harboring an Alteration on ALK, MET or ROS1
NCT02034981
  1. Villejuif, Ile De France
ALL GENDERS
1 Year+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Phase 2 Study Assessing Efficacy and Safety of Crizotinib in Patients Harboring an Alteration on ALK, MET or ROS1
Official Title  ICMJE AcSé CRIZOTINIB : Secured Access to Crizotinib for Patients With Tumors Harboring a Genomic Alteration on One of the Biological Targets of the Drug.
Brief Summary

This is a biology driven, trans-tumoral, multicentric phase II trial assessing the efficacy and the safety of the targeted agent crizotinib as a monotherapy in 23 cohorts of patients with identified activating molecular alterations in the crizotinib target genes. A cohort is defined by a pathology and a crizotinib-target alteration (eg gastric cancer with MET amplification).

For each cohort a two-stage design will be implemented. In the situation where expected accrual allows for a sufficient number of patients to be accrued, the alpha and beta errors will be fixed at 10%. However, in very rare diseases, such as inflammatory myofibroblastic tumor (IMT), neuroblastoma, glioblastoma, and rhabdomyosarcoma (RMS), it is anticipated that the target number may not be achievable in a reasonable timeframe; for these cohorts, the alpha and beta errors will be fixed at 15%. Consequently three different statistical designs will be a priori considered according to the expected response rate and incidence.

Detailed Description

Twenty cohorts are identified, a cohort being defined as [one pathology, one target alteration] such as [gastric cancer with MET amplification (6%)].

One cohort will be dedicated to miscellaneous, very rare pediatric diseases identified through INCa platforms or pan-genome programs (e.g. MOSKIDO, IGR) and will recruit up to 10 patients.

Two cohorts will be dedicated to a couple of diseases harbouring at least one specific alteration in one crizotinib target, same or different from those listed above, e.g. in AXL gene, arising from pan-genome trials.

  1. ALCL, adults and children, ALK-translocated
  2. Colorectal cancer, adults, ALK-translocated
  3. Colorectal cancer, adults, MET amplified
  4. Colorectal cancer, adults, MET mutated
  5. NSCLC, adults, MET amplified
  6. NSCLC, adults, ROS1-translocated
  7. Breast cancer, adults, ALK-translocated
  8. Gastric cancer, adults, MET amplified
  9. Cholangiocarcinoma, adults, ROS1-translocated
  10. Ovarian cancer, adults, MET amplified
  11. Clear cell renal cell carcinoma, adults, ALK-translocated
  12. Clear cell renal cell carcinoma, adults, ALK-amplified
  13. Papillary renal cell carcinoma, adults, MET mutated (+ MET amplified)
  14. Hepatocarcinoma, adults, MET amplified
  15. Neuroblastoma, adults and children, ALK-amplified + ALK mutated
  16. IMT, adults and children, ALK-translocated
  17. Rhabdomyosarcoma (alveolar and embryonal), adults and children, ALK-amplified
  18. Glioblastoma, adults, MET amplified. This cohort will only be open after amendment
  19. Anaplastic thyroid cancer, adults, ALK mutated
  20. Thyroid cancer (follicular + medullary + papillary), adults, MET mutated
  21. Miscellaneous rare pediatric diseases associated to at least one specific alteration in one crizotinib target, same or different from those listed above
  22. One another pathology associated to at least one specific alteration in one crizotinib target, same or different from those listed above.
  23. One another pathology associated to at least one specific alteration in one crizotinib target, same or different from those listed above.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hematologic Cancers
  • Solid Tumors
  • Metastatic Cancer
Intervention  ICMJE Drug: Crizotinib

Patients will receive oral crizotinib, daily continuously, until progression or unacceptable toxicity develops.

-250 mg twice daily for adults ? 18 years of age

  • 280 mg/m² twice daily for children and adolescents aged from 1 to 17 (except ALCL).
  • 165 mg/m² twice daily for ALCL patients aged from 1 to 17.
Other Name: XALKORI
Study Arms  ICMJE Experimental: CRIZOTINIB
All eligible patients entering the study will receive oral crizotinib as monotherapy
Intervention: Drug: Crizotinib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 1, 2018)
246
Original Estimated Enrollment  ICMJE
 (submitted: January 10, 2014)
470
Estimated Study Completion Date  ICMJE July 2022
Actual Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion:

  • Male and female ? 1 year of age
  • unresectable locally advanced or metastatic malignant tumor of any histological type (but NSCLC with an ALK translocation) and not amenable to any other validated therapeutic option. ( for pediatrics a relapse after a first well-conducted standard treatment or a situation without any standard treatment and a survival <10%).
  • one proven specific alterations among ALK, MET, RON and ROS1 genes determined on the primary and/or the metastatic lesion
  • Measurable disease according to RECIST 1.1
  • For patients with primary cerebral tumors (adults or children), measurable disease defined by bi-dimensional measurements : two perpendicular diameters of at least 10 mm on CT or MRI scan, outside of a previously radiated field within the last 3 months, to observe pseudoprogression
  • hematologic function (ANC ? 1.0x10?/L, platelets ? 75x10?/L, platelets ? 50x10?/L for ALCL with bone marrow involved ; platelets ? 100x10?/L for primary or secondary cerebral tumors; Hb ? 8g/L), renal function (creat cl ? 50 mL/min Cockcroft and Gault) and hepatic function (serum bilirubin ? 1.5x ULN unless due to Gilbert's syndrome ; ASAT and ALAT ? 5x ULN if liver metastasis or ? 3x ULN if liver metastasis with advanced fibrosis (FibroTest>0.48) or ? 3x ULN without liver metastasis)
  • normal values for calcium, magnesium and potassium levels
  • able to swallow and retain oral medication
  • ECOG Performance Status of 0 to 2, or Karnofsky scale > 50 % or Lansky Play scale (< 12 years) > 50%, (for CNS tumors, the neurological deficiency due to the disease itself)
  • Life expectancy ? 3 months

Exclusion :

  • NSCLC patients ALK translocations
  • Patient eligible for a clinical trial with an anticancer drug (including crizotinib) targeting the same molecular alteration open to accrual in France.
  • alteration limited to an overexpression of ALK, MET, RON, ROS1 or any other crizotinib-target. Only patients with ALCL are eligible if ALK is positive by immunohistochemistry
  • Patients with primary or secondary central nervous system disease
  • Previous treatment with crizotinib
  • Major surgery or tumor embolization within 4 weeks and minor surgery within 2 weeks prior to the initiation of the study drug. Brain surgery is excluded within 4 weeks prior to starting crizotinib for primary or secondary cerebral tumors
  • Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as, but not limited to :

    • Within the 3 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, or cerebrovascular accident including transient ischemic attack
    • Ongoing congestive heart failure
    • Congenital long QT syndrome
    • Heart rate ? 45 beats/minute
    • Ongoing cardiac dysrhythmias of NCI CTCAE Grade ?2, uncontrolled atrial fibrillation of any grade, or with QTcF interval >470 msec
    • For patients with a cerebral disease (primary or secondary) : uncontrolled hypertension [defined as SBP of ? 140 mmHg or DBP of ? 90mmHg]
    • extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease, including pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis, but not prior radiation pneumonitis
    • Spinal cord compression unless treated with the patient attaining good pain control and stable or recovered neurologic function
    • Carcinomatous meningitis or leptomeningeal disease
    • HIV-positive, active hepatitis A, B or C, or latent hepatitis B or C, or any other uncontrolled infection
    • Other severe acute or chronic medical or psychiatric conditions, or end stage renal disease on hemodialysis or laboratory abnormalities
    • For patients with a cerebral disease, detection on the MRI or the CTscan of a real arteriovenous malformation, or an untreated intracranial aneurysm, or a cavernous angioma, or an amyloid angiopathy, or any new or significant (? grade 2) intratumoral bleeding other than microbleeds on T2* weighted MRI in the previous 14 days before treatment initiation, or a recent and untreated subdural effusion.
  • Patients using non-substitutable drugs that are potent CYP3A4 inhibitors, or potent CYP3A4 inducers
  • Patients using non-substitutable drugs that are CYP3A4 substrates with narrow therapeutic indices
  • Patients with cerebral disease using anti-platelet drugs or anticoagulant agents are not eligible if those treatments can not be stopped 7 days before day1.
  • Patients with altered mental status or with psychological, familial, sociological or geographical condition potentially hampering compliance
  • Individual deprived of liberty or placed under the authority of a tutor.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 1 Year and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02034981
Other Study ID Numbers  ICMJE UC-0105/1303
2013-000885-13 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party UNICANCER
Study Sponsor  ICMJE UNICANCER
Collaborators  ICMJE
  • National Cancer Institute, France
  • Fondation ARC
  • Pfizer
Investigators  ICMJE
Principal Investigator:Gilles VASSALGustave Roussy, Villejuif
PRS Account UNICANCER
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP