Secured access to crizotinib for patients with tumors harboring a genomic alteration on one of the biological targets of the drug - AcSé crizotinib

• Register: EUCTR
• Last refreshed on: 21 September 2015
• Main ID: EUCTR2013-000885-13-FR
• Date of registration: 22/04/2013
• Prospective Registration: Yes
• Primary sponsor: UNICANCER
• Public title: Secured access to crizotinib for patients with tumors harboring a genomic alteration on one of the biological targets of the drug - AcSé crizotinib
• Scientific title: Secured access to crizotinib for patients with tumors harboring a genomic alteration on one of the biological targets of the drug - AcSé crizotinib
• Date of first enrolment: 31/07/2013
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000885-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

France

Contacts

• Name: Head of Personalized Medicine
• Affiliation: UNICANCER

• Name: Head of Personalized Medicine
• Affiliation: UNICANCER

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female = 1 year of age
2. Diagnosis of unresectable locally advanced or metastatic malignant tumor (solid tumor or hematological malignancy) of any histological type (but Non Small Cell Lung Cancer with an ALK derived translocation) and considered by the investigator as not amenable to any other validated therapeutic option
3. At least one proven specific alterations among ALK, MET, RON and ROS1 genes determined on the primary and/or the metastatic lesion such as
• Any type of ALK translocation in Anaplastic Large Cell Lymphoma (ALCL), breast cancer, colorectal cancer, myofibroblastic inflammatory tumor and renal cell carcinoma
• ALK amplification/copy number gain (CNG) in rhabdomyosarcoma, renal cell carcinoma, neuroblastoma
• ALK mutation in neuroblastoma and anaplastic thyroid cancer
• MET amplification/CNG in gastric cancer, ovarian cancer, colorectal cancer, glioblastoma, hepatocarcinoma and NSCLC
• MET mutation in thyroid cancer as well as papillary renal cell carcinoma and colorectal cancer
• ROS1 translocation in cholangiocarcinoma and NSCLC
• RON mutation and amplification/CNG in gastric cancer (in a secondary phase of the trial)
• Any other pathology, except CNS tumors, harbouring one of these alterations, including in genomic AXL gene
Patients included in pangenomic research programs harbouring specific alterations in at least one crizotinib target different from those listed above (i.e AXL, etc.) are also eligible
The list of alterations, oncogenic variants and other target genes may be upgraded during the progress of the study considering the level of proof
4. Measurable disease according to RECIST 1.1 guidelines 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
5. Patients who had received any previous systemic anticancer treatment and/or radiotherapy should have recovered from any treatment related toxicity, i.e. = grade1, with a mandatory free interval of at least 3 weeks for systemic treatments, and at least 5 half-lives for targeted drugs. ALCL patients receiving vincristine, vinblastine or non-hematologically toxic compounds can have a wash-out period shortened to 2 weeks
6. Patients who had received any investigational drug are eligible after a 4-week wash-out period or a wash-out period equivalent to 5 half-lifes of the product, depending on the longest period
7. Adequate hematologic function (ANC = 1.0x109/L, platelets = 75x109/L, platelets = 50x109/L for ALCL with bone marrow involved ; Hb = 8g/L), renal function (creatinine clearance = 60mL/min using Cockroft and Gault formula) and hepatic function (serum bilirubin = 1.5x ULN unless due to Gilbert’s syndrome ; ASAT and ALAT = 5x ULN if documented liver metastasis or = 3x ULN if documented liver metastasis associated with advanced fibrosis (FibroTest>0.48) or = 3x ULN without liver metastasis)
8. Patients presenting strictly normal values for calcium and magnesium levels, measured within 14 days of the treatment initiation, and strictly normal values for potassium level measured within 72 hours of the treatment initiation
9. Patients able to swallow and retain oral medication
10. ECOG Performance Status of 0 to 2, or Karnofsky scale > 50 % or Lansky Play scale (< 12 years) > 50%
11. Life expectancy = 3 months
12. Potentially reproductive patients must agree to use an effectiv
Exclusion criteria:
1. Non Small Cell Lung Cancer patients harbouring ALK derived translocations
2. Patient eligibile for a clinical trial with an anticancer drug (including crizotinib) targeting the same molecular alteration in the patient’s pathology open to accrual in France. Patients not eligible in this trial are still eligible for the AcSé study
3. Genomic alteration limited to an overexpression of ALK, MET, RON, ROS1 or any other crizotinib-target (i.e. without increased copy number or structural gene alteration) will not be sufficient for eligibility. Only patients with ALCL are eligible if their tumor is ALK positive as evidenced by immunohistochemistry
4. Patients with primary or secondary CNS disease
5. Previous treatment with crizotinib
6. Major surgery or tumor embolization within 4 weeks and minor surgery within 2 weeks prior to the initiation of the study drug
7. Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as, but not limited to :
a) Any of the following 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
b) Ongoing congestive heart failure
c) Congenital long QT syndrome
d) Heart rate = 45 beats/minute
e) Ongoing cardiac dysrhythmias of NCI CTCAE Grade =2, uncontrolled atrial fibrillation of any grade, or machine-read ECG with QTcF interval >470 msec
f) 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
g) Spinal cord compression unless treated with the patient attaining good pain control and stable or recovered neurologic function
h) Carcinomatous meningitis or leptomeningeal disease
i) Known HIV-positive, known active hepatitis A, B or C, or latent hepatitis B or C, or any other uncontrolled infection
j) Other severe acute or chronic medical (including severe gastrointestinal conditions such as diarrhea or ulcer) or psychiatric conditions, or end stage renal disease on hemodialysis or laboratory abnormalities that would impart, 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
8. Patients using drugs that are known potent CYP3A4 inhibitors, (including but not limited to atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole), or potent CYP3A4 inducers (including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John’s Wort=millepertuis in French) are not eligible if those treatments can not be substituted
9. Patients using non-substitutable drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited to dihydroergotamine, aripiprazole, ergotamine, halofantrine, pimozide, triazolam astemizole, cisapride, and terfenadine
10. Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geograph

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with metastatic or unresectable locally advanced malignancies harboring specific genomic alterations regarding the biological crizotinib targets, and who are no more amenable to curative treatment
MedDRA version: 14.1 Level: LLT Classification code 10007050 Term: Cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10029260 Term: Neuroblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10002227 Term: Anaplastic large cell lymphoma T- and null-cell types System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10067917 Term: Inflammatory myofibroblastic tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10008593 Term: Cholangiocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10067946 Term: Renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10039022 Term: Rhabdomyosarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: LLT Classification code 10024658 Term: Liver carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10061873

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: XALKORI®
Product Name: Crizotinib
Pharmaceutical Form: Capsule
INN or Proposed INN: CRIZOTINIB
CAS Number: 877399-52-5
Other descriptive name: CRIZOTINIB
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 200-250

Product Name: Crizotinib
Pharmaceutical Form: Oral solution
INN or Proposed INN: CRIZOTINIB
CAS Number: 877399-52-5
Other descriptive name: CRIZOTINIB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Primary end point(s): Anti-tumor activity of crizotinib, as the primary objective of the trial, will be carried out by the determination of the confirmed objective response rate (complete or partial response according to RECIST 1.1), assessed in each cohort defined by a pathology associated with a crizotinib target alteration.

Main Objective: The objective of this study is to explore the efficacy of crizotinib as a single agent across diverse type of tumors guided by the presence of identified activating molecular alterations in the crizotinib-target genes, per cohort, per pathology and per target.

Secondary Objective: - To assess the safety profile of crizotinib
- To explore whether molecularly driven, high quality multi-tumor screening Phase II trials are feasible in the French multiinstitutional, multidisciplinary setting.

Secondary Outcome(s)

Secondary end point(s): - Disease control rate
- Response duration
- Progression-free survival
- Overall Survival
- Safety (CTCAE v4.0)
- Correlative research endpoints

Secondary ID(s)

UC-0105/1303

Source(s) of Monetary Support

NON COMMERCIAL FRENCH ORGANISATION