Hepatic Impairment Study For Crizotinib In Advanced Cancer Patients

NCT01576406

Last updated date
Study Location
Keck Hospital of USC
Los Angeles, California, 90033, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Advanced Cancer
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Histologically or cytologically confirmed solid malignancy or lymphoma that is metastatic or unresectable, and for which standard curative or palliative measures do not exist, or are no longer effective. In case of hepatocellular carcinoma, the diagnosis should be based on at least one of the following:

1. The presence of at least one lesion, measuring ≥ 2 cm, with characteristic arterial enhancement and venous washout in the setting of liver cirrhosis and/or hepatitis B or C infection.

2. The presence of liver lesion(s) (as defined in a.) with AFP ≥ 400 ng/mL.

3. Tissue confirmation.

- Biliary obstruction for whom a biliary drain or stent has been placed are eligible, provided that the drain or stent have been in place for at least 10 days prior to the first dose of crizotinib, and the liver function has stabilized as defined by 2 measurements at least 5 days apart that put the patient in the same hepatic dysfunction stratum as defined in Section 3.

- Presence of gliomas and brain metastases only if neurologically stable and treated without ongoing requirement for corticosteroids for at least 2 weeks.

- Any prior systemic therapy (e.g., chemotherapy, molecularly targeted agent, immunotherapy, etc.) or major surgery must have been completed at least 30 days (or as determined by the local requirement, whichever is longer), or at least 5 half lives for drugs with half lives of 6 days or longer prior to initiation of crizotinib treatment. Any prior radiation (except palliative) or minor surgeries/procedures must have been completed at least 2 weeks prior to the initiation of crizotinib treatment. Palliative radiation (≤ 10 fractions) must have been completed 48 hours prior to the initiation of crizotinib treatment. Any acute toxicity must have recovered to Grade ≤1 (except alopecia).

- Eastern Cooperative Oncology Group [ECOG] performance status 0-2.

- Adequate organ function for patients receiving crizotinib therapy as defined by the following criteria:

Bone marrow function

- Absolute neutrophil count (ANC) ≥ 750/uL

- Platelets ≥ 30,000/uL

- Hemoglobin ≥ 8.0 g/dL (≥ 7.0 g/dL for hematologic malignancy) Renal function

- Creatinine ≤ 1.5 x ULN or CrCl > 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional 1.5 x ULN

- Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- Untreated esophageal varices observed on EGD or imaging study; however, patients with
known portal hypertension and evidence of varices on EGD or imaging study who have
undergone appropriate therapy as indicated within the last 6 months (if applicable)
are eligible for enrollment.


- Uncontrolled ascites that is not stable with medical management (i.e., on diuretics
and salt restriction) as defined by requiring therapeutic paracentesis more than once
every 4 weeks.


- Episodes of hepatic encephalopathy within the last 4 weeks. Patients with prior
episodes of hepatic encephalopathy who are clinically stable on lactulose, neomycin,
and/or xifaxan therapy are allowed.


- Prior therapy with crizotinib.


- Spinal cord compression.


- Carcinomatous meningitis or leptomeningeal disease


- Any of the following within the 6 months prior to starting study treatment: myocardial
infarction, severe/unstable angina, coronary/peripheral artery bypass graft, or
cerebrovascular accident including transient ischemic attack.


- Symptomatic congestive heart failure.


- Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥ 2, uncontrolled atrial fibrillation
of any grade, or an average of triplicate QTc interval >470 msec.


- History of extensive disseminated/bilateral or known presence of 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.


- Active hemolysis or evidence of biliary sepsis.


- Pregnant females; breastfeeding females; males and females of childbearing potential;
males and females of childbearing potential not using highly effective contraception
or not agreeing to continue highly effective contraception for at least 28 days after
last dose of investigational product; males and females of childbearing potential not
using two (2) methods of highly effective contraception or not agreeing to continue
two (2) methods of highly effective contraception for at least 28 days after last dose
of investigational product.


- 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.


- Use of drugs that are known strong CYP3A4 inducers, including but not limited to
carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort.


- Use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but
not limited to dihydroergotamine, ergotamine, and pimozide.


- Other severe acute or chronic medical (may include severe gastrointestinal conditions
such as chronic diarrhea or ulcer disease) or psychiatric conditions, or laboratory
abnormalities that may increase the risk associated with study participation or study
drug administration or may interfere with the interpretation of the study results and,
in the judgment of the investigator, would make the patient inappropriate for study
entry.


- Patients who had prior major gastrointestinal surgery removing part of
gastrointestinal tract and/or gall bladder.

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Advanced Information
Descriptive Information
Brief Title  ICMJE Hepatic Impairment Study For Crizotinib In Advanced Cancer Patients
Official Title  ICMJE A Phase I Study To Evaluate The Effect Of Hepatic Impairment On The Pharmacokinetics And Safety Of Crizotinib In Advanced Cancer Patients
Brief Summary This study is designed to evaluate the potential effect of hepatic impairment on the pharmacokinetics and safety of crizotinib in advanced cancer patients. Advanced cancer patients with mild, moderate or severe liver dysfunction as well as patients with normal liver function will be enrolled in this study.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Advanced Cancer
Intervention  ICMJE
  • Drug: crizotinib
    crizotinib 250 mg twice a day
  • Drug: crizotinib
    crizotinib 250 mg once a day
Study Arms  ICMJE
  • Experimental: A1: normal hepatic function
    Intervention: Drug: crizotinib
  • Experimental: A2: normal hepatic function
    Intervention: Drug: crizotinib
  • Experimental: B: mild hepatic impairment
    Intervention: Drug: crizotinib
  • Experimental: C: moderate hepatic impairment
    Intervention: Drug: crizotinib
  • Experimental: D: severe hepatic impairment
    Intervention: Drug: crizotinib
Publications * El-Khoueiry AB, Sarantopoulos J, O'Bryant CL, Ciombor KK, Xu H, O'Gorman M, Chakrabarti J, Usari T, El-Rayes BF. Evaluation of hepatic impairment on pharmacokinetics and safety of crizotinib in patients with advanced cancer. Cancer Chemother Pharmacol. 2018 Apr;81(4):659-670. doi: 10.1007/s00280-018-3517-8. Epub 2018 Feb 21.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: January 5, 2018)
88
Original Estimated Enrollment  ICMJE
 (submitted: April 10, 2012)
50
Actual Study Completion Date  ICMJE June 2016
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed solid malignancy or lymphoma that is metastatic or unresectable, and for which standard curative or palliative measures do not exist, or are no longer effective. In case of hepatocellular carcinoma, the diagnosis should be based on at least one of the following:

    1. The presence of at least one lesion, measuring ? 2 cm, with characteristic arterial enhancement and venous washout in the setting of liver cirrhosis and/or hepatitis B or C infection.
    2. The presence of liver lesion(s) (as defined in a.) with AFP ? 400 ng/mL.
    3. Tissue confirmation.
  • Biliary obstruction for whom a biliary drain or stent has been placed are eligible, provided that the drain or stent have been in place for at least 10 days prior to the first dose of crizotinib, and the liver function has stabilized as defined by 2 measurements at least 5 days apart that put the patient in the same hepatic dysfunction stratum as defined in Section 3.
  • Presence of gliomas and brain metastases only if neurologically stable and treated without ongoing requirement for corticosteroids for at least 2 weeks.
  • Any prior systemic therapy (e.g., chemotherapy, molecularly targeted agent, immunotherapy, etc.) or major surgery must have been completed at least 30 days (or as determined by the local requirement, whichever is longer), or at least 5 half lives for drugs with half lives of 6 days or longer prior to initiation of crizotinib treatment. Any prior radiation (except palliative) or minor surgeries/procedures must have been completed at least 2 weeks prior to the initiation of crizotinib treatment. Palliative radiation (? 10 fractions) must have been completed 48 hours prior to the initiation of crizotinib treatment. Any acute toxicity must have recovered to Grade ?1 (except alopecia).
  • Eastern Cooperative Oncology Group [ECOG] performance status 0-2.
  • Adequate organ function for patients receiving crizotinib therapy as defined by the following criteria:

Bone marrow function

  • Absolute neutrophil count (ANC) ? 750/uL
  • Platelets ? 30,000/uL
  • Hemoglobin ? 8.0 g/dL (? 7.0 g/dL for hematologic malignancy) Renal function
  • Creatinine ? 1.5 x ULN or CrCl > 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional 1.5 x ULN

    • Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.

Exclusion Criteria:

  • Untreated esophageal varices observed on EGD or imaging study; however, patients with known portal hypertension and evidence of varices on EGD or imaging study who have undergone appropriate therapy as indicated within the last 6 months (if applicable) are eligible for enrollment.
  • Uncontrolled ascites that is not stable with medical management (i.e., on diuretics and salt restriction) as defined by requiring therapeutic paracentesis more than once every 4 weeks.
  • Episodes of hepatic encephalopathy within the last 4 weeks. Patients with prior episodes of hepatic encephalopathy who are clinically stable on lactulose, neomycin, and/or xifaxan therapy are allowed.
  • Prior therapy with crizotinib.
  • Spinal cord compression.
  • Carcinomatous meningitis or leptomeningeal disease
  • Any of the following within the 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, or cerebrovascular accident including transient ischemic attack.
  • Symptomatic congestive heart failure.
  • Ongoing cardiac dysrhythmias of NCI CTCAE Grade ? 2, uncontrolled atrial fibrillation of any grade, or an average of triplicate QTc interval >470 msec.
  • History of extensive disseminated/bilateral or known presence of 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.
  • Active hemolysis or evidence of biliary sepsis.
  • Pregnant females; breastfeeding females; males and females of childbearing potential; males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 28 days after last dose of investigational product; males and females of childbearing potential not using two (2) methods of highly effective contraception or not agreeing to continue two (2) methods of highly effective contraception for at least 28 days after last dose of investigational product.
  • 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.
  • Use of drugs that are known strong CYP3A4 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort.
  • Use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited to dihydroergotamine, ergotamine, and pimozide.
  • Other severe acute or chronic medical (may include severe gastrointestinal conditions such as chronic diarrhea or ulcer disease) or psychiatric conditions, or laboratory abnormalities that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of the study results and, in the judgment of the investigator, would make the patient inappropriate for study entry.
  • Patients who had prior major gastrointestinal surgery removing part of gastrointestinal tract and/or gall bladder.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01576406
Other Study ID Numbers  ICMJE A8081012
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date January 2018

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