Sunitinib for Advanced Thymus Cancer Following Earlier Treatment

NCT01621568 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 12011812-C-0118
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Sunitinib is drug that is approved for treating various types of cancers, including kidney cancers. However, it has not been approved to treat cancers of the thymus. Sunitinib works by blocking proteins that are responsible for cell division and growth. Some of these proteins can be found on thymus cancer cells. Researchers want to see if sunitinib can be used to treat advanced thymus cancer. It will be given to people who have had at least one earlier chemotherapy treatment containing platinum. Objectives: \- To see if sunitinib is a safe and effective treatment for advanced thymus cancer that has not responded to earlier treatments. Eligibility:

• Individuals at least 18 years of age who have advanced thymus cancer that has not responded to earlier treatments.
• At least one previous cancer treatment must have been chemotherapy treatment containing platinum. Design:
• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies and tumor biopsies will be used to check the severity of the cancer.
• Participants will take sunitinib tablets once a day, in the morning. They will take the tablets daily for 4 weeks, followed by 2 weeks of rest with no sunitinib. This 6-week period is called a cycle.
• Treatment will be monitored with frequent blood tests and imaging studies.
• Treatment cycles may be repeated as long as the tumor does not continue to grow and there are no severe side effects....

Conditions

Thymoma; Thymus Neoplasms

Keywords

VEGF; Anti-Angiogenesis; Targeted Agent

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With an Objective Response (Partial Response (PR) + Complete Response (CR) for Sunitinib in Participants With Relapsed or Refractory Thymoma or Thymic Carcinoma

  Objective response rate (CR + PR) will be measured according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for sunitinib monotherapy in participants with advanced thymic malignancies. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  A median duration of 6 months

Secondary Outcomes (3)

• Progression-free Survival for Sunitinib in Participants With Relapsed or Refractory Thymoma or Thymic Carcinoma

  An average of 10 months

• Number of Participants Alive at 1 Year After Treatment With Sunitinib

  12 months after initiation of treatment

• Number of Grades ≥3 Adverse Events Related to Sunitinib

  Date treatment consent signed to date off study, approximately 110 months and 28 days for the thymoma/thymic carcinoma group and 91 months and 11 days for the thymic carcinoma only group.

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

  Date treatment consent signed to date off study, approximately 110 months and 28 days for the thymoma/thymic carcinoma group and 91 months and 11 days for the thymic carcinoma only group.

Study Arms (2)

Group 1 (Thymoma and thymic carcinoma)

EXPERIMENTAL

Group 1 (Thymoma and thymic carcinoma) treated with sunitinib 50 mg/day, 4 weeks on, 2-weeks off (6 week cycle).

Drug: Sunitinib

Group 2 (Thymic carcinoma only)

EXPERIMENTAL

Group 2 (Thymic carcinoma only) treated with sunitinib 50 mg/day, 2 weeks on, 1 week off (3 week cycle).

Drug: Sunitinib

Interventions

Sunitinib DRUG

50mg/day for 4 weeks daily, by mouth with 2 weeks off (6 week cycle)

Also known as: Sutent

Group 1 (Thymoma and thymic carcinoma)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological confirmation of thymoma (Group 1 only) or thymic carcinoma by the pathology department/Center for Cancer Research (CCR)/national Cancer Institute (NCI) or the pathology department of participating institutions.
• At least one prior line of platinum-based chemotherapy or patient must have refused cytotoxic chemotherapy. Progressive disease must be documented prior to study entry.
• Patients must not have received chemotherapy, radiation therapy, or undergone major surgery within 4 weeks prior to enrollment.
• Patients must have measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky \> 50 percent)
• Life expectancy of greater than 3 months.
• Patients must have normal organ and marrow function as defined below:
• hemoglobin greater than or equal to 9 g/dL
• leukocytes greater than or equal to 3,000/mcL
• absolute neutrophil count greater than or equal to 1,200/mcL
• platelets greater than or equal to 100,000/mcL
• total bilirubin within normal institutional limits
• serum calcium less than or equal to 12.0 mg/dL
• Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT)/alanine transaminase (ALT)/serum glutamic-pyruvic transaminase (SGPT) less than or equal to 2.5 times institutional upper limit of normal

You may not qualify if:

• Patients with tumor amenable to potentially curative therapy.
• Prior treatment within the past 6 months with sunitinib, sorafenib, bevacizumab or other multikinase inhibitors targeting any of the following: vascular endothelial growth factors 1 3 (VEGF1 3), FMS-like tyrosine kinase 3 (FLT3), stem cell growth factor (c-KIT), platelet-derived growth factors-alpha and -beta (PDGF-alpha,-beta), colony-stimulating factor 1 (CSF1), and the RET receptor for glial-derived neurotrophic factors.
• Patients with symptomatic brain metastases will be excluded from trial secondary to poor prognosis. However, patients who have had treatment for their brain metastasis and whose brain disease has remained stable for 3 months without steroid therapy may be enrolled.
• Patients with evidence of severe or uncontrolled systemic disease, or any concurrent condition, which could compromise participation in the study, including, but not limited to, active or uncontrolled infection, immune deficiencies, uncontrolled hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection unless sustained virologic response to HCV therapy, uncontrolled diabetes, serious non-healing ulcer, wound or bone fracture, history of intra-abdominal abscess, abdominal fistula or gastrointestinal perforation within 28 days of treatment, history of pulmonary embolism in the past 12 months, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry, Class III or IV heart failure as defined by the NYHA functional classification system, stroke/cerebrovascular accident or transient ischemic attack within the past 12 months or psychiatric illness/social situations which would jeopardize compliance with the protocol.
• History of a previous invasive malignancy within the last 5 years, except adequately treated non-melanoma skin cancer, papillary carcinoma of the thyroid or carcinoma in situ of the uterine cervix.
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib. Patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) are ineligible. (A list of potent CYP3A4 inducers or inhibitors can be found in Section 5.2.) An exception will be made for patients who are on ritonavir-based highly active antiretroviral therapy, in which case the starting dose of sunitinib will be modified as indicated in Sections 5.1.1 and 5.2.12. Every effort should be made to switch patients taking such agents or substances to other medications. A comprehensive list of medications and substances known or with the potential to alter the pharmacokinetics of sunitinib through CYP3A4 is provided.
• Pregnant women are excluded from this study because sunitinib angiogenesis inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sunitinib breastfeeding should be discontinued if the mother is treated with sunitinib.
• Patients who require therapeutic doses of Coumadin derivative anticoagulants such as warfarin are excluded. Low molecular weight heparin is permitted, provided the patient's prothrombin time (PT)/INR is less than or equal to 1.5. Coumadin doses of up to 2 mg daily are permitted for prophylaxis of thrombosis.
• Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible.
• Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain sunitinib tablets are excluded.
• Patients with QTc prolongation (defined as a QTc interval equal to or greater than 500 msec) or other significant electrocardiogram (ECG) abnormalities are excluded.
• Patients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 91 mmHg or higher) are ineligible.
• Patients who require use of therapeutic doses of coumarin derivative anticoagulants such as warfarin are excluded, although doses of up to 2 mg daily are permitted for prophylaxis of thrombosis. Note: Low molecular weight heparin is permitted provided the patient's PT INR is less than or equal to 1.5.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Indiana University School of Medicine: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Detterbeck FC. Clinical value of the WHO classification system of thymoma. Ann Thorac Surg. 2006 Jun;81(6):2328-34. doi: 10.1016/j.athoracsur.2005.11.067.

  PMID: 16731193 BACKGROUND

• Engels EA, Pfeiffer RM. Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer. 2003 Jul 1;105(4):546-51. doi: 10.1002/ijc.11099.

  PMID: 12712448 BACKGROUND

• Falkson CB, Bezjak A, Darling G, Gregg R, Malthaner R, Maziak DE, Yu E, Smith CA, McNair S, Ung YC, Evans WK; Lung Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-Based Care. The management of thymoma: a systematic review and practice guideline. J Thorac Oncol. 2009 Jul;4(7):911-9. doi: 10.1097/jto.0b013e3181a4b8e0.

  PMID: 19557895 BACKGROUND

• Thomas A, Rajan A, Berman A, Tomita Y, Brzezniak C, Lee MJ, Lee S, Ling A, Spittler AJ, Carter CA, Guha U, Wang Y, Szabo E, Meltzer P, Steinberg SM, Trepel JB, Loehrer PJ, Giaccone G. Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial. Lancet Oncol. 2015 Feb;16(2):177-86. doi: 10.1016/S1470-2045(14)71181-7. Epub 2015 Jan 13.

  PMID: 25592632 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Thymoma; Thymus Neoplasms

Interventions

Sunitinib

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Arun Rajan
• Organization: National Cancer Institute

rajana@mail.nih.gov

240-760-6236

Study Officials

• Arun Rajan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 14, 2012
• First Posted: June 18, 2012
• Study Start: May 15, 2012
• Primary Completion: April 30, 2021
• Study Completion: July 31, 2024
• Last Updated: September 24, 2024
• Results First Posted: June 7, 2022

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)