Clinical trial NCT04030429: Crizotinib in c-MET Mutation Metastatic/Recurrent/Persistent Endometrial Cancer
Official title: Phase II Trial of Crizotinib in c-MET Mutation Metastatic/Recurrent/Persistent Endometrial Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Endometrial Cancer Recurrent
Lead sponsor: National Cheng-Kung University Hospital
Sponsor class: OTHER
Collaborators: name: Chi Mei Medical Hospital
name: Kaohsiung Medical University
name: Kaohsiung Veterans General Hospital.
First posted: 2019-07-24
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: In this phase 2 study, the target population is patients with recurrent or persistent metastatic endometrial cancer. The mutation status of c-MET gene will be tested and only patients with c-MET mutation will be enrolled. After enrollment, Crizotinib 250 mg bid will be used orally. CT scan or MRI will be used to determine the response. Crizotinib will be continued till disease progression. Primary end is objective response rate. The secondary endpoints include progression-free survival, overall survival and safety profiles.

Eligibility 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.

Primary outcomes:
measure: Change in best overall response rate
timeFrame: CT scan or MRI will be done at baseline and at the end of every 2 cycles (each cycle is 28 days) until the date of first documented progression or date of death from any cause, whichever came first, up to 104 weeks
Secondary outcomes:
measure: Progression-free survival
timeFrame: CT scan or MRI will be done at baseline and at the end of every 2 cycles (each cycle is 28 days) until the date of first documented progression or date of death from any cause, whichever came first, up to 104 weeks
measure: Overall survival
timeFrame: Overall survival will be followed from the start of treatment to death from any cause, up to 104 weeks
Other outcomes:
Locations:
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
Study officials:
affiliation: National Cheng-Kung University Hospital
name: Keng-Fu Hsu, PhD
role: PRINCIPAL_INVESTIGATOR
References: