Clinical Trials /

CRIZENT: Crizotinib and Sunitinib in Metastatic Breast Cancer

NCT02074878

Description:

This is a Phase 1 Trial. Crizotinib is a medication that is taken by mouth. It has shown that it can help slow down or stop the growth of tumor cells. The marketing name of the drug is "Xalkori". It has been approved by the FDA (Food and Drug Administration) to treat other types of metastatic cancer, but the investigators believe it may be helpful to treat breast cancer as well. Sunitinib is the other medication used in the study. It is also taken by mouth in the form of a capsule. The marketing name of this drug is "Sutent". It too has been approved by the FDA to treat other types of cancer, but not for breast cancer. In this study the investigators will be combining both of these two treatments, but at different doses. One third of the patients will take Crizotinib 200 mg, twice daily with Sunitinib 25.0 mg once a day. One third of the patients will take Crizotinib 250 mg, twice daily with Sunitinib 25.0 mg once a day, and One third of the patients will take Crizotinib 250 mg, twice daily with Sunitinib 37.5 mg once a day.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CRIZENT: Crizotinib and Sunitinib in Metastatic Breast Cancer
  • Official Title: A Phase IB Study of Crizotinib (XALKORI) and Sunitinib (SUTENT) in Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: H-33624
  • NCT ID: NCT02074878

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Crixotinib 200 mg and Sunitinib Cohort 1Crizotinib (Xalkori) 200 mg twice daily, Sunitinib (Sutent) 25.0 mg once a dayCrixotinib 200 mg and Sunitinib Cohort 1
Crixotinib 250 mg and Sunitinib Cohort 2Crixotinib (Xalkori) 250, Sunitinib (Sutent) 25.0Crixotinib 250 mg and Sunitinib Cohort 2
Crizotinib & Sunitinib 37.5 mg Cohort 3Crizotinib (Xalkori) 250 mg, Sunitinib (Sutent) 37.5 mgCrizotinib & Sunitinib 37.5 mg Cohort 3

Purpose

This is a Phase 1 Trial. Crizotinib is a medication that is taken by mouth. It has shown that it can help slow down or stop the growth of tumor cells. The marketing name of the drug is "Xalkori". It has been approved by the FDA (Food and Drug Administration) to treat other types of metastatic cancer, but the investigators believe it may be helpful to treat breast cancer as well. Sunitinib is the other medication used in the study. It is also taken by mouth in the form of a capsule. The marketing name of this drug is "Sutent". It too has been approved by the FDA to treat other types of cancer, but not for breast cancer. In this study the investigators will be combining both of these two treatments, but at different doses. One third of the patients will take Crizotinib 200 mg, twice daily with Sunitinib 25.0 mg once a day. One third of the patients will take Crizotinib 250 mg, twice daily with Sunitinib 25.0 mg once a day, and One third of the patients will take Crizotinib 250 mg, twice daily with Sunitinib 37.5 mg once a day.

Detailed Description

      This study will determine the safety and tolerability of the combination of crizotinib and
      sunitinib in the treatment of Metastatic Breast Cancer and help to establish the maximum
      tolerated dose for future phase II studies of the combination.
    

Trial Arms

NameTypeDescriptionInterventions
Crixotinib 200 mg and Sunitinib Cohort 1ExperimentalCrizotinib 200mg, twice daily and Sunitinib 25.0mg once daily
  • Crixotinib 200 mg and Sunitinib Cohort 1
Crixotinib 250 mg and Sunitinib Cohort 2ExperimentalCrizotinib 250 mg, twice daily with Sunitinib 25.0 mg once a day
  • Crixotinib 250 mg and Sunitinib Cohort 2
Crizotinib & Sunitinib 37.5 mg Cohort 3ExperimentalCrizotinib 250 mg, twice daily with Sunitinib 37.5 mg once a day
  • Crizotinib & Sunitinib 37.5 mg Cohort 3

Eligibility Criteria

        Inclusion Criteria:

          1. Subjects must provide written informed consent prior to performance of study-specific
             procedures or assessments, and must be willing to comply with treatment and follow-up.

          2. Age of at least 18 years

          3. Histologically confirmed diagnosis of stage IV, HER2 negative breast cancer.

          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

          5. Patients must have failed two lines of systemic therapy for breast cancer. Patients
             who are hormone receptor positive must have failed at least one line of hormonal
             therapy AND one line of chemotherapy in the metastatic setting.

          6. Life expectancy of 6 months or more.

          7. Liver function (ALT, AST, alkaline phosphatase, total bilirubin) and kidney function
             tests (BUN, creatinine) less than 2.5 times the upper limit of normal. In patients
             with liver metastasis, liver function tests should be less than 5 times the upper
             limit of normal.

          8. Adequate blood counts (Hemoglobin greater than/equal to 10, WBC greater than/equal to
             3.0, platelets greater than/equal to 100).

          9. The patient has normal thyroid function tests (TSH, free T4) as defined by the testing
             laboratory, a test abnormality that is asymptomatic and does not warrant medical
             intervention, or a pre-existing thyroid disorder that is controlled on medical
             treatment.

         10. Negative pregnancy test (BHCG) within 14 days of study drug initiation for pre- or
             perimenopausal subjects with an intact uterus.

        Exclusion Criteria:

          1. Clinically significant gastrointestinal abnormalities that may increase the risk for
             gastrointestinal bleeding.

          2. Clinically significant gastrointestinal abnormalities that may affect absorption of
             investigational products.

          3. Presence of uncontrolled infection.

          4. Corrected QT interval (QTc) > 480 msecs using Bazett's formula

          5. History of any one or more of the following cardiovascular conditions within the past
             6 months: - Cardiac angioplasty or stenting - Myocardial infarction - Unstable angina
             - Coronary artery bypass graft surgery - Symptomatic peripheral vascular disease -
             Class III or IV congestive heart failure, as defined by the New York Heart Association
             (NYHA)

          6. Poorly controlled hypertension (defined as systolic blood pressure [SBP] of > 150 mmHg
             or diastolic blood pressure [DBP] of > 90 mmHg).

          7. History of cerebrovascular accident including transient ischemic attack (TIA),
             pulmonary embolism, or untreated deep venous thrombosis (DVT) within the past 6
             months. Subjects with recent DVT who have been treated with therapeutic
             anti-coagulating agents for at least 6 weeks are eligible.

          8. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
             presence of any non-healing wound, fracture, or ulcer (procedures such as catheter
             placement not considered to be major).

          9. Evidence of active bleeding or bleeding diathesis.

         10. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

         11. Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks prior to first
             dose of study drug.

         12. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that
             could interfere with subject's safety, provision of informed consent, or compliance to
             study procedures.

         13. Patients previously treated with sunitinib or crizotinib.

         14. History of other malignancy within the last 5 years, except for carcinoma in situ of
             the cervix or basal cell carcinoma of the skin.

         15. Concurrent use of: - Potent CYP3A4 inhibitors: ketoconazole, itraconazole,
             clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir,
             amprenavir, indinavir, nelfinavir, delavirdine and voriconazole. - CYP3A4 inducers:
             rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, St. John's
             Wort, and dexamethasone. Use of dexamethasone for study premedication is allowed. -
             Grapefruit and grapefruit juice. (Note: Alternative therapies should be used when
             available. If use of a potent CYP3A4 inhibitor or inducer is necessary, this must be
             approved by the principal investigator and documented in source documents).

         16. History of receiving any investigational treatment within 28 days of study medication
             initiation.

         17. Current severe, uncontrolled systemic disease (e.g., clinically significant
             cardiovascular, pulmonary, thyroid, or metabolic disease; wound healing disorders;
             ulcers; or bone fractures).

         18. Patients who are pregnant or lactating.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose of the treatment drugs in the patients that are taking it.
Time Frame:1 year
Safety Issue:
Description:To determine the tolerability of the combination of crizotinib and sunitinib in the treatment of women with metastatic breast cancer (MBC). - This is done by identifying the maximum tolerated dose (MTD) for future phase II studies of the combination of crizotinib and sunitinib.

Secondary Outcome Measures

Measure:Changes that occur in tumor tissue before treatment and after treatment.
Time Frame:2 years
Safety Issue:
Description:Assess the clinical activity of the combination regimen in patients with MBC. - This is done by performing exploratory correlative studies on tissue acquired from accessible metastatic lesions based on serial biopsies performed at baseline and recording changes in biomarker levels between responders vs. non-responders.
Measure:Laboratory results to make sure the treatment is safe.
Time Frame:1 year
Safety Issue:
Description:Safety and toxicity parameters will be summarized using descriptive statistics. All patients who received any amount of study drugs will be included in the safety analysis. Safety analyses will include summaries of adverse event rates (both frequency and incidence tables), baseline laboratory parameters and changes from baseline, frequency of CTCAE toxicity grades for both laboratory and non-laboratory data.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Mothaffar Rimawi

Trial Keywords

  • Breast Cancer
  • Metastatic
  • Crizotinib
  • Sunitinib
  • Xalcori
  • Sutent

Last Updated

August 8, 2017