Lenvatinib in Second Line Endometrial Carcinoma

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Endometrial Neoplasms
• Intervention / Treatment: Drug: Doxorubicin; Drug: Lenvatinib

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Lausanne, Switzerland
    • Centre Hospitalier Universitaire Vaudois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenvatinib; Lenvatinib 24 mg orally every day. Treatment is continued until unacceptable toxicity, progressive disease or patient withdrawal	Drug: Lenvatinib
Active Comparator: Doxorubicin; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Investigators: Study Chair: Antonio Casado, Hospital Universitario San Carlos, Madrid, Spain

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Anticipated): July 1, 2020

Study Registration Dates

• First Submitted: August 18, 2016
• First Submitted That Met QC Criteria: December 23, 2016
• First Posted (Estimate): December 29, 2016

Study Record Updates

• Last Update Posted (Estimate): December 29, 2016
• Last Update Submitted That Met QC Criteria: December 23, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Lenvatinib
• Other Study ID Numbers: EORTC-1528