Crizotinib in c-MET Mutation Metastatic/Recurrent/Persistent Endometrial Cancer

• Status: Not yet recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The majority of endometrial cancer patients with disease spread beyond the uterus will progress within 1 year. Platinum-based chemotherapy was used as the first-line treatment in metastatic or advanced endometrial cancer. There is no standard protocol for the second-line option when tumors persist or recur. In vitro and in vivo studies showed Crizotinib, an approved drug for the treatment of ALK-positive non-small cell lung cancer, demonstrated activities in endometrial cancer with c-MET kinase and Sema domain mutations. As a consequence, a phase 2 clinical trial to investigate the efficacy of Crizotinib in endometrial cancer patients with MET mutation is initiated.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cheng-Kung University Hospital
• Collaborators: Chi Mei Medical Hospital; Kaohsiung Medical University; Kaohsiung Veterans General Hospital.
• Treatments: Crizotinib

Criteria

Inclusion Criteria:

• Age no less than 20 years and no more than 75 years, at the time of acquisition of informed consent.

• Histological confirmed epithelial endometrial cancer

• Disease recurrent after curative therapy or adjuvant therapy including surgery, chemotherapy, radiotherapy or hormone therapy

• Metastatic/recurrent/persistent endometrial cancer

• Tumor tissue with high expression in immunohistochemistry stain (IHC) or somatic c-MET mutation

• Patients with symptomatic recurrent lesion or Image diagnosis (including ultrasound, Computed Tomography or Magnetic Resonance Imaging) recurrent status

• ECOG Performance status 0-2

• At least one distinct tumor, not previous irradiated, measurable lesion according to RECIST (version 1.1)

• Adequate organ function

Bone marrow:

Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L WBC ≥ 3.0 x 10^9/L Platelet count ≥ 100 x 10^9/L Hemoglobin ≥ 9 g/dL

Hepatic:

Total bilirubin level ≤ 1.0 x UNL AST and ALT ≤ 3.0 x UNL Renal: Creatinine level ≤ 1.5 mg/dL in men, ≤1.4 mg/dL in women; or Estimated CCr ≥ 60 mL/min (CCr is estimated by Cockcroft-Gault formula)

• Negative pregnancy test for women of childbearing potential only

• Patient willing to provide blood sample for research purposes

• Written informed consent

Exclusion Criteria:

• Presence or history of malignancy disease other than endometrial cancer that has been diagnosed with past five years

• Other anti-tumor agent such as systemic chemotherapy, hormone therapy or surgery within 2 weeks before the commencement of study treatment or radiotherapy within 4 weeks before the commencement of study

• Active uncontrolled infection

• Significant medical diseases, such as unstable angina, acute or recent myocardial infarction (<6 months before enrollment), COPD with frequent exacerbation, uncontrolled hypertension, ore cent CVA (<6 months before enrollment)

• Poor compliance

• Pregnant or breastfeeding women, where pregnancy is confirmed by a positive hCG laboratory test.