Lenvatinib in Second Line Endometrial Carcinoma

Study Overview
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Brief Summary
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The primary objective of this multicenter, randomized phase II trial is to assess the efficacy, as measured by progression-free survival (PFS), of lenvatinib compared to doxorubicin in advanced or recurrent endometrial cancer. The main secondary objective is to evaluate the predictive value of Ang-2 on lenvatinib activity and establishing a cutoff value as potential selection criteria for phase III. Other secondary objectives are to assess the tolerability and safety of lenvatinib in this setting and overall survival, response and disease control.

Official Title
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A Randomized Phase II Study of Lenvatinib Versus Doxorubicin in Second Line Advanced or Recurrent Endometrial Carcinoma

Conditions
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Endometrial Neoplasms

Intervention / Treatment
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* Drug: Lenvatinib
* Drug: Doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects age ≥18 years at the time of informed consent World Health Organization (WHO) Performance Status of 0 or 1 Patients with histologically confirmed endometrial cancer including serous-papillary and clear cell histologies. Uterine carcinosarcomas are allowed. Radiographic evidence of disease progression according to RECIST 1.1 after 1 prior systemic, platinum-based chemotherapy regimen for metastatic or primary unresectable endometrial carcinoma for which no surgical or radiotherapy treatment options exist. Patients with disease progression following platinum-based chemotherapy administered as either adjuvant or neoadjuvant treatment are also eligible. Patients may have received prior radiotherapy and / or adjuvant chemotherapy for early high-risk disease Patients may not have received prior treatment with anthracyclines Blood samples available for retrospective central assessment of Ang-2 level Patients may have had prior therapy providing the following conditions are met: Surgery and radiation therapy: wash-out period of 14 days and subjects must have recovered adequately from any toxicity and/or complications from radiotherapy and major surgery prior to starting therapy. Systemic anti-tumor therapy or any investigational agent: wash-out period of 21 days (or 5 x half-life) Recovery from any toxic effects of prior therapy to ≤ Grade 1 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.) except alopecia Adequate contraceptive measures Signed written informed consent Exclusion Criteria: Inadequate hematologic, renal and hepatic functions Abnormal cardiac function

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenvatinib<br>Lenvatinib 24 mg orally every day. Treatment is continued until unacceptable toxicity, progressive disease or patient withdrawal | Drug: Lenvatinib<br> <br> |
| Active Comparator: Doxorubicin<br>Doxorubicin 60 mg/m² iv bolus every 3 weeks. Treatment is continued for a maximum of 6 cycles or until unacceptable toxicity, progressive disease or patient withdrawal. | Drug: Doxorubicin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | PFS assessed by Response Evaluation Criteria in Solid Tumors (RECIST | 2.5 years |