Crizotinib Efficacy In Non-Small Cell Lung Cancer Patients With Anaplastic Lymphoma Kinase Translocation

July 20, 2016 updated by: National Taiwan University Hospital

An Exploratory Study Of Crizotinib Efficacy In Non-Small Cell Lung Cancer Patients With Anaplastic Lymphoma Kinase Translocation Determined By Different Molecular Diagnostic Methods

This is an exploratory study in patients with locally advanced or metastatic Non-small cell lung cancer. Patients who are eligible to apply for Extended Access Program of crizotinib must have ALK translocation detected by RT-PCR, IHC or FISH analyses methods.

Study Overview

Status

Unknown

Conditions

Detailed Description

This is an exploratory non-randomized study in patients with locally advanced or metastatic NSCLC. Patients who are eligible to apply for Extended Access Program of crizotinib must have ALK translocation detected by RT-PCR, IHC or FISH analyses methods. Patients who failed and progressed through at least one line of platinum containing chemotherapy and who are older than 70 years old with failure of chemotherapy will be eligible for this study. We will screen EML4-ALK fusion gene by RT-PCR (HotSart Taq Master Mix Kits, Qiaqen) from patients' malignant pleural effusions and the detail was described in previous study[1]. We will also use IHC analyses (5A4 monoclonal antibody, Novocastra) to screen ALK protein expression in patients' FFPE tumor sections. We will further do FISH analysis by using commercial Vysis LSI ALK Dual Color, Break Apart Rearrangement Probe (2p23) (Abott Molecular Inc., Des Plaines, IL) to detect ALK rearrangement in positive screening tumors. Samples are deemed to be FISH-positive if more than 15% of 50 scored tumor cells had split ALK 5' and 3' probe signals or had isolated 3' signals[5]. Patients who have ALK rearrangement determined in any of 3 molecular analyses methods and apply for crizotinib will receive 250mg of crizotinib twice daily until disease progression, unacceptable toxicities or the withdrawal of consent is noted.

Patients will be monitored carefully for the development of adverse experiences. Adverse experiences will be evaluated according to criteria outlined in the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Patients will also be monitored for clinical and/or radiographic evidence of disease progression according to RECIST 1.1.

The primary endpoint of the study is overall response rate in patients with positive ALK determined from different molecular analysis methods. The secondary endpoint included overall response in specific subsets of patients, progression-free survival (PFS), and overall survival (OS) at 1 year. PFS is defined as the time from day 1 of crizotinib to disease progression or patient's death. OS was defined as the time from day 1 of crizotinib treatment to patient's death.

During the treatment, patients will have safety measurements performed at specified time points. Disease response will be assessed during the study by radiographic (e.g., CT or MRI), and clinical (e.g., physical examination) evaluations, if applicable. Overall tumor response will be assessed at the designated time points (every 12 weeks, using Response Evaluation Criteria in Solid Tumors (RECIST, Version 1.1). The crizotinib treatment could be continued after RECIST-defined disease progression if clinical benefit is still noted by primary physician.

Study Type

Observational

Enrollment (Actual)

12

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Taipei, Taiwan, 100
        • Department of Oncology, National Taiwan University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with locally advanced or metastatic NSCLC who are eligible to apply for Extended Access Program of crizotinib must have ALK translocation detected by RT-PCR, IHC or FISH analyses methods.

Description

Inclusion Criteria:

  1. Patient must have locally advanced or metastatic NSCLC (Stage IIIb or Stage IV by AJCC 7th.) with positive ALK determined by RT-PCR or IHC (5A4, 3+ score). Patients must have failed and progressed through at least one line of platinum containing chemotherapy or failed and progressed through chemotherapy if they were older than 70 years old.
  2. Patient must have at least one measurable lesion.
  3. Patient is male or female and ≥ 20 years of age on the day of signing informed consent.
  4. Patient must have performance status ≤ 2 on the ECOG Performance Scale.
  5. Patient must have adequate organ function as indicated by the following laboratory values: adequate liver (total bilirubin < 1.5 x the upper limit of normal (ULN), total bilirubin > 1.5 x ULN but biliary obstruction is documented radiologically, transaminases < 2.5 x ULN or < 5 x ULN if due to liver metastases), renal (creatinine < 2 x ULN) and bone marrow function (hemoglobin > 8g/dL, absolute neutrophil count > 1 X 109/L and platelets > 30 X 109/L)
  6. Female patient of childbearing potential has a negative serum or urine pregnancy test β-hCG within 5 days prior to receiving the first dose of study medication.
  7. Patients have completed chemotherapy regimens have residual toxicity < Grade 1 except alopecia.
  8. Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent.
  9. Patient is able to swallow capsules and has no surgical or anatomical condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis.

Exclusion Criteria:

  1. Patient who has had chemotherapy within 2 weeks prior to Day 1 of Cycle 1 or has not recovered from the adverse events due to previous agents prior to Day 1 of Cycle 1. If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade 1 except alopecia.
  2. Patient who has had major surgery within 4 weeks prior to starting of treatment or expect major surgery in the study duration. Patient who has had prior radiotherapy (except brain) within 1 week prior to Day 1 of Cycle 1.
  3. Patient is currently participating or has participated in a study with an investigational compound or device within 30 days, or 5x half-life from prior agents, whichever is longer, of Day 1 of this study.
  4. Patient has known active CNS metastases and/or carcinomatous meningitis unless patients were clinically stable for 2 weeks after radiotherapy.
  5. Patient with a primary central nervous system tumor.
  6. Patient has known hypersensitivity to the components of study drug or its analogs.
  7. Patient has severe systemic disease.
  8. Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
  9. Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  10. Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse.
  11. Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
  12. Patient is known to be Human Immunodeficiency Virus (HIV)-positive
  13. Patient currently has active Hepatitis B which is defined as patient has positive serum HBsAg with ALT > 2 x ULN and HBV DNA > 20,000 IU/mL.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall response rate in patients with positive ALK determined from different molecular analysis methods.
Time Frame: It is defined as the time from day 1 of crizotinib to disease progression or patient's death.
It is defined as the time from day 1 of crizotinib to disease progression or patient's death.

Secondary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival (PFS)
Time Frame: 1 year
1 year
Overall survival (OS)
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: James Chih-Hsin Yang, MD, PhD, National Taiwan University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (Anticipated)

December 1, 2016

Study Completion (Anticipated)

March 1, 2017

Study Registration Dates

First Submitted

June 28, 2012

First Submitted That Met QC Criteria

July 10, 2012

First Posted (Estimate)

July 11, 2012

Study Record Updates

Last Update Posted (Estimate)

July 21, 2016

Last Update Submitted That Met QC Criteria

July 20, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Other Study ID Numbers

  • 201204080RIC

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Non-small Cell Lung Cancer(NSCLC)

Search Similar Trials