A Study of Sunitinib in Patients With Metastatic or Recurrent Thymic Carcinoma (KOSMIC)

A Phase II, Non-comparative, Open Label, Multi-center Study of Sunitinib in Patients With Metastatic or Recurrent Thymic Carcinoma

This study aims to investigate the clinical activity of sunitinib in patients with advanced thymic carcinoma who have failed chemotherapy.

Study Overview

• Status: Completed
• Conditions: Thymic Carcinoma
• Intervention / Treatment: Drug: Sunitinib

Detailed Description

Sunitinib (Sutent®; Pfizer, New York, NY, USA) is a multitargeted tyrosine-kinase inhibitor (TKI) with activity against the stem cell-factor receptor (KIT) and platelet-derived growth-factor receptor (PDGFR), vascular endothelial growth-factor receptor (VEGFR), glial cell line-derived neurotrophic factor receptor (rearranged during transfection [RET]), colony-stimulating factor-1 receptor (CSF1R), and Fms-like tyrosine kinase-3 receptor (FLT3).

Sunitinib is a potent inhibitor of mutant KIT with additional inhibitory effects on VEGF receptors that potentially might make it more effective than imatinib against TCs. In the current version of NCCN guideline, sunitinib is suggested as one of the potential targeted therapeutics for advanced TCs.

We planned this study to investigate the clinical efficacy and tolerability of sunitinib in patients with advanced or recurrent TCs in Korean population. In addition, we will collect tumor samples and blood samples from patients for the further exploration of predictive biomarkers.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seongnam, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of signed, written and dated informed consent prior to any study specific procedures
2. Histopathologically confirmed metastatic or recurrent thymic thymic carcinoma
3. Age ≥ 20
4. ECOG PS 0-2
5. Documented progressive disease after one or more conventional systemic chemotherapy
6. At least one measurable disease by RECIST v1.1

7. Adequate organ function for treatment as follows:

   • Absolute neutrophil count > 1.5 x 109/L
   • Platelets >100 x 109/L
   • Serum creatinine ≤ 2.0 x ULN (upper limit of normal)
   • Serum bilirubin ≤ 1.5 x ULN
   • AST and ALT ≤ 2.5 x ULN (without liver metastasis), ≤ 5.0 x ULN (with liver metastasis)
8. Life expectancy ≥ 12 weeks at day 1

Exclusion Criteria:

1. Previous treatment with sunitinib or other VEGF-TKIs
2. Any major operation or irradiation within 4 weeks of baseline disease assessment
3. Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug
4. CNS metastasis with continuous corticosteroid use within 4 weeks of baseline disease assessment (Asymptomatic CNS metastasis patients can be enrolled)
5. Patients with uncontrolled or significant cardiovascular disease (AMI within 12 months, Unstable angina within 6 months, NYHA Class III, IV Congestive heart failure or left ventricular ejection fraction below local institutional lower limit of normal or below 45%, Congenital long QT syndrome, Any significant ventricular arrhythmia, Any uncontrolled second or third degree heart block, Uncontrolled hypertension)
6. Concomitant malignancy (except adequately treated basal cell cancer of skin or cervical cancer in situ)
7. Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
8. Other severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial. (including active bleeding, untreated DVT or thromboembolism)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sunitinib; Sunitinib will be administered orally at a dose of 50 mg once daily in 3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment.	Drug: Sunitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	CR or PR by RECIST criteria version 1.1	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate	CR or PR or SD by RECIST criteria version 1.1	Up to 6 months
Progression-Free Survival		Up to 6 months
Overall survival		From first day of study treatment to day of any kind of death, assessed up to 24 months
Incidence of treatment related adverse events [Safety and Tolerability]	Number of patients with adverse events during cycle 1 (each cycle is 21 days). Subjects will be evaluated for toxicity according to NCI-CTCAE(Common Terminology Criteria for Adverse Events) of version 4.0.	Up to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker endpoint	When available, banked tumor tissue for genomic analysis for predictive biomarker of sunitinib.	Day 1

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: SMG-SNU Boramae Medical Center
• Investigators: Principal Investigator: Jong Seok Lee, MD, PhD, Seoul National University Bundang Hospital

Publications and helpful links

Helpful Links

• Oral Presentation at WCLC 2018 (OA11.05 )

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: October 28, 2015
• First Submitted That Met QC Criteria: December 2, 2015
• First Posted (Estimate): December 7, 2015

Study Record Updates

• Last Update Posted (Actual): January 23, 2019
• Last Update Submitted That Met QC Criteria: January 18, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Metastatic; Recurrent; Sunitinib; Thymic carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Thoracic Neoplasms; Neoplasms, Complex and Mixed; Thymus Neoplasms; Carcinoma; Thymoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: SNUBH-15-01